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 557129050  36 GIFGQKLEDTVRYEKRYGNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASL 115
Cdd:cd04390    1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 116 LKLYLRELPEPVVPYAKYEDFLSCATLLSKEEEAGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLAT 195
Cdd:cd04390   81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 557129050 196 VFGPNILRPKVEDPLTIMEGTVVVQQLMSVMISKHDRLF 234
Cdd:cd04390  161 VFGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 557129050  558 KQEMTKQKIEYESRIKSLEQrnltletEMLSLHDELDQERKKFTMIEIKMRNAERAKEDAEKRNDMLQKEMEQF 631
Cdd:pfam20492   1 REEAEREKQELEERLKQYEE-------ETKKAQEELEESEETAEELEEERRQAEEEAERLEQKRQEAEEEKERL 67

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 557129050  36 GIFGQKLEDTVRYEKRYGNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASL 115
Cdd:cd04390    1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 116 LKLYLRELPEPVVPYAKYEDFLSCATLLSKEEEAGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLAT 195
Cdd:cd04390   81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 557129050 196 VFGPNILRPKVEDPLTIMEGTVVVQQLMSVMISKHDRLF 234
Cdd:cd04390  161 VFGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050   58 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFD-SNTDVHTVASLLKLYLRELPEPVVPYAKYEDF 136
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDlEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050  137 LSCATLLSKEEeaGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNILRPKV 206
Cdd:pfam00620  81 IEAAKLPDEEE--RLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                           10        20
                   ....*....|....*....|....*...
gi 557129050     2 TANHESYLLMASTQNDMEDWVKSIRRVI 29
Cdd:smart00233  74 TSDRKTLLLQAESEEEREKWVEALRKAI 101

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 557129050  36 GIFGQKLEDTVRYEKRYGNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASL 115
Cdd:cd04390    1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 116 LKLYLRELPEPVVPYAKYEDFLSCATLLSKEEEAGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLAT 195
Cdd:cd04390   81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 557129050 196 VFGPNILRPKVEDPLTIMEGTVVVQQLMSVMISKHDRLF 234
Cdd:cd04390  161 VFGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

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 557129050    58 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFD-SNTDVHTVASLLKLYLRELPEPVVPYAKYEDF 136
Cdd:smart00324   4 PIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDlSEYDVHDVAGLLKLFLRELPEPLITYELYEEF 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050   137 LSCATLLSKEEeaGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNILRPKVEDPLTIMEgT 216
Cdd:smart00324  84 IEAAKLEDETE--RLRALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLKD-I 160

                          170
                   ....*....|....
gi 557129050   217 VVVQQLMSVMISKH 230
Cdd:smart00324 161 RHQNTVIEFLIENA 174

RhoGAP_nadrin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Nadrin-like proteins. Nadrin, also named Rich-1, has been shown to be involved in the regulation of Ca2+-dependent exocytosis in neurons and recently has been implicated in tight junction maintenance in mammalian epithelium. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050  37 IFGQKLEDTVryeKRYGNRLApMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCG--EKPSFDSNTDVHTVAS 114
Cdd:cd04386    4 VFGTPLEEHL---KRTGREIA-LPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGtfSLPLDEFYSDPHAVAS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 115 LLKLYLRELPEPVVPYAKYEDFLSCATLLSKEEEagVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLA 194
Cdd:cd04386   80 ALKSYLRELPDPLLTYNLYEDWVQAANKPDEDER--LQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIA 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 557129050 195 TVFGPNILRPKVEDPLTIME--GTVVVQQLMSVMISKHDRLFPKD 237
Cdd:cd04386  158 IVLAPNLLWAKNEGSLAEMAagTSVHVVAIVELIISHADWFFPGE 202

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 557129050  38 FGQKLEDTVryEKRYGNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASLLK 117
Cdd:cd04404    6 FGVSLQFLK--EKNPEQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYEDVHLPAVILK 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 118 LYLRELPEPVVPYAKYEDFLSCATLLSKEEEAGVKELmkqVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVF 197
Cdd:cd04404   84 TFLRELPEPLLTFDLYDDIVGFLNVDKEERVERVKQL---LQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVF 160

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 557129050 198 GPNILRPKveDPLTIMEGTVVVQQLMSVMISKHDRLF 234
Cdd:cd04404  161 GPNLLWAK--DASMSLSAINPINTFTKFLLDHQDEIF 195

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 557129050  58 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDC-GEKPSFDSNT--DVHTVASLLKLYLRELPEPVVPYAKYE 134
Cdd:cd04372   17 PMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRdGEKADISATVypDINVITGALKLYFRDLPIPVITYDTYP 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 135 DFLSCATLLSKEEEagvKELMKQ-VKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNILRPKVEDPLTIM 213
Cdd:cd04372   97 KFIDAAKISNPDER---LEAVHEaLMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPPEDSALTTL 173

                        170       180
                 ....*....|....*....|.
gi 557129050 214 EGTVVVQQLMSVMISKHDRLF 234
Cdd:cd04372  174 NDMRYQILIVQLLITNEDVLF 194

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 557129050  58 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASLLKLYLRELPEPVVPYAKYEDFL 137
Cdd:cd04382   18 PALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNLSKVDIHVICGCLKDFLRSLKEPLITFALWKEFM 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 138 SCATLLSkeEEAGVKELMKQVKSLPVVNYNLLKYICRFLDEVqSYSGVNKMSAQNLATVFGPNILRPKVEDP--LTIMEG 215
Cdd:cd04382   98 EAAEILD--EDNSRAALYQAISELPQPNRDTLAFLILHLQRV-AQSPECKMDINNLARVFGPTIVGYSVPNPdpMTILQD 174

                        170
                 ....*....|...
gi 557129050 216 TVVVQQLMSVMIS 228
Cdd:cd04382  175 TVRQPRVVERLLE 187

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 557129050  38 FGQKLEDTVRYEkrygNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDS--NTDVHTVASL 115
Cdd:cd04403    1 FGCHLEALCQRE----NSTVPKFVRLCIEAVEKRGLDVDGIYRVSGNLAVIQKLRFAVDHDEKLDLDDskWEDIHVITGA 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 116 LKLYLRELPEPVVPYAKYEDFLsCATLLSKEEE--AGVKELmkqVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNL 193
Cdd:cd04403   77 LKLFFRELPEPLFPYSLFNDFV-AAIKLSDYEQrvSAVKDL---IKSLPKPNHDTLKMLFRHLCRVIEHGEKNRMTTQNL 152

                        170
                 ....*....|....
gi 557129050 194 ATVFGPNILRPKVE 207
Cdd:cd04403  153 AIVFGPTLLRPEQE 166

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 557129050  38 FGQKLED-TVRYEKRYGNRLAPMLVEQCVDFIRQ-RGLKEEGLFRLPGQANLVKELQDAFDCGEKPsfDSNT-DVHTVAS 114
Cdd:cd04389    1 FGSSLEEiMDRQKEKYPELKLPWILTFLSEKVLAlGGFQTEGIFRVPGDIDEVNELKLRVDQWDYP--LSGLeDPHVPAS 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 115 LLKLYLRELPEPVVPYAKYEDFLScatllSKEEEAGVKELmkqVKSLPVVNYNLLKYICRFLDEV--QSYSGVNKMSAQN 192
Cdd:cd04389   79 LLKLWLRELEEPLIPDALYQQCIS-----ASEDPDKAVEI---VQKLPIINRLVLCYLINFLQVFaqPENVAHTKMDVSN 150

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 557129050 193 LATVFGPNILRPKVEDPLTIMEGTVVVQQLMSVMI 227
Cdd:cd04389  151 LAMVFAPNILRCTSDDPRVIFENTRKEMSFLRTLI 185

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 557129050  36 GIFGQKLEDTVRYEkrygNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFD--SNTDVHTVA 113
Cdd:cd04383    1 KLFNGSLEEYIQDS----GQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADdqNDHDINSVA 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 114 SLLKLYLRELPEPVVPYAKYEDFLSCATLLSKEEEagVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNL 193
Cdd:cd04383   77 GVLKLYFRGLENPLFPKERFEDLMSCVKLENPTER--VHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNL 154

                        170
                 ....*....|....*..
gi 557129050 194 ATVFGPNILR-PKVEDP 209
Cdd:cd04383  155 AICFGPTLMPvPEGQDQ 171

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 557129050  56 LAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKP--SFDSNTDVHTVASLLKLYLRELPEPVVP---Y 130
Cdd:cd04387   15 KVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDvsVMLSEMDVNAIAGTLKLYFRELPEPLFTdelY 94

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 557129050 131 AKYEDFLSCATLLSKEEEagvkeLMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNILRPKVED 208
Cdd:cd04387   95 PNFAEGIALSDPVAKESC-----MLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKE 167

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 557129050  58 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASLLKLYLRELPEPVVPYAKYEDFL 137
Cdd:cd04407   16 PIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLENYPIHAITGLLKQWLRELPEPLMTFAQYNDFL 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 138 SCATLLSKEEE-AGVKELMKQvksLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNILR-PKVEDPLTIMEG 215
Cdd:cd04407   96 RAVELPEKQEQlQAIYRVLEQ---LPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRcPDSSDPLTSMKD 172

                        170
                 ....*....|..
gi 557129050 216 ----TVVVQQLM 223
Cdd:cd04407  173 vaktTTCVEMLI 184

RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of CdGAP-like proteins; CdGAP contains an N-terminal RhoGAP domain and a C-terminal proline-rich region, and it is active on both Cdc42 and Rac1 but not RhoA. CdGAP is recruited to focal adhesions via the interaction with the scaffold protein actopaxin (alpha-parvin). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050  37 IFGQKLEDtvrYEKRYGNRLaPMLVEQCVDFIRQRGLKEeGLFRLPGQANLVKELQDAFDCGEKP---SFDSNTDVHTVA 113
Cdd:cd04384    2 VFGCDLTE---HLLNSGQDV-PQVLKSCTEFIEKHGIVD-GIYRLSGIASNIQRLRHEFDSEQIPdltKDVYIQDIHSVS 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 114 SLLKLYLRELPEPVVPYAKYEDFLSCATLLSKEEEagVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNL 193
Cdd:cd04384   77 SLCKLYFRELPNPLLTYQLYEKFSEAVSAASDEER--LEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNL 154

                        170
                 ....*....|..
gi 557129050 194 ATVFGPNILRPK 205
Cdd:cd04384  155 AIVWAPNLLRSK 166

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 557129050  38 FGQKLEDTVRYEKRY-GNRLaPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDsNTDVHTVASLL 116
Cdd:cd04381    1 FGASLSLAVERSRCHdGIDL-PLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRESPNLE-EYEPPTVASLL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 117 KLYLRELPEPVVP---YAKYEDflSCATLLSKEEEAGVKELMKQvksLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNL 193
Cdd:cd04381   79 KQYLRELPEPLLTkelMPRFEE--ACGRPTEAEREQELQRLLKE---LPECNRLLLAWLIVHMDHVIAQELETKMNIQNI 153

                 ....*...
gi 557129050 194 ATVFGPNI 201
Cdd:cd04381  154 SIVLSPTV 161

RhoGAP_OCRL1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in OCRL1-like proteins. OCRL1 (oculocerebrorenal syndrome of Lowe 1)-like proteins contain two conserved domains: a central inositol polyphosphate 5-phosphatase domain and a C-terminal Rho GAP domain, this GAP domain lacks the catalytic residue and therefore maybe inactive. OCRL-like proteins are type II inositol polyphosphate 5-phosphatases that can hydrolyze lipid PI(4,5)P2 and PI(3,4,5)P3 and soluble Ins(1,4,5)P3 and Ins(1,3,4,5)P4, but their individual specificities vary. The functionality of the RhoGAP domain is still unclear. 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 557129050  63 QCVDFIRQRGLKEEGLFRLPGQ----ANLVKELQDAFDCGEkpSFDSNTDVHTVASLLKLYLRELPEPVVPYAKYEDFLS 138
Cdd:cd04380   56 RLVDYLYTRGLAQEGLFEEPGLpsepGELLAEIRDALDTGS--PFNSPGSAESVAEALLLFLESLPDPIIPYSLYERLLE 133

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 557129050 139 CATLLSkeeeagvkELMKQV--KSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNILRPKVEDP 209
Cdd:cd04380  134 AVANNE--------EDKRQVirISLPPVHRNVFVYLCSFLRELLSESADRGLDENTLATIFGRVLLRDPPRAG 198

RhoGAP_Graf: GTPase-activator protein (GAP) domain for Rho-like GTPases found in GRAF (GTPase regulator associated with focal adhesion kinase); Graf is a multi-domain protein, containing SH3 and PH domains, that binds focal adhesion kinase and influences cytoskeletal changes mediated by Rho proteins. Graf exhibits GAP activity toward RhoA and Cdc42, but only weakly activates Rac1. 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 557129050  59 MLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAF------DCGEKPSFDSNTDVHTVASLLKLYLRELPEPVVPYAK 132
Cdd:cd04374   30 KFVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGldpktsTPGDVDLDNSEWEIKTITSALKTYLRNLPEPLMTYEL 109

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557129050 133 YEDFLSCATllSKEEEAGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNILRPKVEDPLTI 212
Cdd:cd04374  110 HNDFINAAK--SENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEETVAAI 187

                 ..
gi 557129050 213 ME 214
Cdd:cd04374  188 MD 189

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 557129050  52 YGNrLAPMLVEQCvDFIRQRgLKEEGLFRLPGQANLVKELQDAFDCGEkpSFDSNTDVHTVASLLKLYLRELPEPVVPYA 131
Cdd:cd04394   17 YGN-VPKFLVDAC-TFLLDH-LSTEGLFRKSGSVVRQKELKAKLEGGE--ACLSSALPCDVAGLLKQFFRELPEPLLPYD 91

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 557129050 132 KYEDFLSCATLLSKEEEAGVKELMKQVksLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNIL 202
Cdd:cd04394   92 LHEALLKAQELPTDEERKSATLLLTCL--LPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLF 160