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 170671704 129 GIFGQKLEDTVRYEKRYGNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASL 208
Cdd:cd04390    1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 209 LKLYLRELPEPVVPYAKYEDFLSCATLLSKEEEAGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLAT 288
Cdd:cd04390   81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 170671704 289 VFGPNILRPKVEDPLTIMEGTVVVQQLMSVMISKHDRLF 327
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 170671704  651 KQEMTKQKIEYESRIKSLEQrnltletEMLSLHDELDQERKKFTMIEIKMRNAERAKEDAEKRNDMLQKEMEQF 724
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 170671704 129 GIFGQKLEDTVRYEKRYGNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASL 208
Cdd:cd04390    1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 209 LKLYLRELPEPVVPYAKYEDFLSCATLLSKEEEAGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLAT 288
Cdd:cd04390   81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 170671704 289 VFGPNILRPKVEDPLTIMEGTVVVQQLMSVMISKHDRLF 327
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 170671704  151 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFD-SNTDVHTVASLLKLYLRELPEPVVPYAKYEDF 229
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDlEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704  230 LSCATLLSKEEeaGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNILRPKV 299
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        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704    19 TKCGWLRKQG-GFVKTWHTRWFVLKGDQLYYFKDEDE---TKPLGTIFLHGNKVIEHPCNEENPGKFLFEVVpggerdrm 94
Cdd:smart00233   2 IKEGWLYKKSgGGKKSWKKRYFVLFNSTLLYYKSKKDkksYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIK-------- 73

                           90       100
                   ....*....|....*....|....*...
gi 170671704    95 TANHESYLLMASTQNDMEDWVKSIRRVI 122
Cdd:smart00233  74 TSDRKTLLLQAESEEEREKWVEALRKAI 101

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 170671704  651 KQEMTKQKIEYESRIKSLEQrnltletEMLSLHDELDQERKKFTMIEIKMRNAERAKEDAEKRNDMLQKEMEQF 724
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 170671704 129 GIFGQKLEDTVRYEKRYGNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASL 208
Cdd:cd04390    1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 209 LKLYLRELPEPVVPYAKYEDFLSCATLLSKEEEAGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLAT 288
Cdd:cd04390   81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 170671704 289 VFGPNILRPKVEDPLTIMEGTVVVQQLMSVMISKHDRLF 327
Cdd:cd04390  161 VFGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704  20 KCGWLRKQGGFVKTWHTRWFVLKGDQLYYFKDEDETKPLGTIFLHGNKVIEHPCNEENPGKFLFEVVPGGERDRMTANHE 99
Cdd:cd13263    5 KSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGGDRMTSNHD 84

                         90       100       110
                 ....*....|....*....|....*....|
gi 170671704 100 SYLLMASTQNDMEDWVKSIRRVIWGPFGGG 129
Cdd:cd13263   85 SYLLMANSQAEMEEWVKVIRRVIGSPFGGG 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704  151 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFD-SNTDVHTVASLLKLYLRELPEPVVPYAKYEDF 229
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDlEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704  230 LSCATLLSKEEeaGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNILRPKV 299
Cdd:pfam00620  81 IEAAKLPDEEE--RLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704  20 KCGWLRKQGGFVKTWHTRWFVLKGDQLYYFKDEDETKPLGTIFLHGNKVIEHPCNEENPGKFLFEVVPGGERDR--MTAN 97
Cdd:cd13378    5 KAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDEEETKPQGCISLQGSQVNELPPNPEEPGKHLFEILPGGAGDRekVPMN 84

                         90       100       110
                 ....*....|....*....|....*....|..
gi 170671704  98 HESYLLMASTQNDMEDWVKSIRRVIWGPFGGG 129
Cdd:cd13378   85 HEAFLLMANSQSDMEDWVKAIRRVIWAPFGGG 116

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 170671704 130 IFGQKLEDtVRYEKRYGNRLaPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASLL 209
Cdd:cd04393    2 VFGVPLQE-LQQAGQPENGV-PAVVRHIVEYLEQHGLEQEGLFRVNGNAETVEWLRQRLDSGEEVDLSKEADVCSAASLL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 210 KLYLRELPEPVVPYAKYEDFLSCATLLSKEEEAGvKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATV 289
Cdd:cd04393   80 RLFLQELPEGLIPASLQIRLMQLYQDYNGEDEFG-RKLRDLLQQLPPVNYSLLKFLCHFLSNVASQHHENRMTAENLAAV 158

                        170
                 ....*....|....
gi 170671704 290 FGPNI--LRPKVED 301
Cdd:cd04393  159 FGPDVfhVYTDVED 172

RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP21-like proteins. ArhGAP21 is a multi-domain protein, containing RhoGAP, PH and PDZ domains, and is believed to play a role in the organization of the cell-cell junction complex. It has been shown to function as a GAP of Cdc42 and RhoA, and to interact with alpha-catenin and Arf6. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 147 NRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCG--EKPSFDSN-TDVHTVASLLKLYLRELPEPVVPY 223
Cdd:cd04395   15 NPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGgfDIDLQDPRwRDVNVVSSLLKSFFRKLPEPLFTN 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 224 AKYEDFLSCATLLSKEEEagVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNILRPKvEDPL 303
Cdd:cd04395   95 ELYPDFIEANRIEDPVER--LKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTS-DDNM 171

                        170       180
                 ....*....|....*....|....*
gi 170671704 304 TIMEGTVVVQ-QLMSVMISKHDRLF 327
Cdd:cd04395  172 ETMVTHMPDQcKIVETLIQHYDWFF 196

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 170671704 131 FGQKLEDTVRYEkrygNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEK-----PSFDSNTDVHTV 205
Cdd:cd04398    1 FGVPLEDLILRE----GDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLnvlliSPEDYESDIHSV 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 206 ASLLKLYLRELPEPVVPYAKYEDFLSCATllSKEEEAGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQN 285
Cdd:cd04398   77 ASLLKLFFRELPEPLLTKALSREFIEAAK--IEDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNN 154

                        170
                 ....*....|
gi 170671704 286 LATVFGPNIL 295
Cdd:cd04398  155 LAIIWGPTLM 164

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 170671704 130 IFGQKLEDTVRYE-KRYGNRLAPMLVEQCVDFI-RQRGLKEEGLFRLPGQANLVKELQDAFDC-GEKPSFDSNT--DVHT 204
Cdd:cd04400    1 IFGSPLEEAVELSsHKYNGRDLPSVVYRCIEYLdKNRAIYEEGIFRLSGSASVIKQLKERFNTeYDVDLFSSSLypDVHT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 205 VASLLKLYLRELPEPVVPYAKYEDFLSCATLLSKEEEAgVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQ 284
Cdd:cd04400   81 VAGLLKLYLRELPTLILGGELHNDFKRLVEENHDRSQR-ALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLR 159

                        170
                 ....*....|..
gi 170671704 285 NLATVFGP--NI 294
Cdd:cd04400  160 NVCIVFSPtlNI 171

RhoGAP_ARHGAP6: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP6-like proteins. ArhGAP6 shows GAP activity towards RhoA, but not towards Cdc42 and Rac1. ArhGAP6 is often deleted in microphthalmia with linear skin defects syndrome (MLS); MLS is a severe X-linked developmental disorder. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 151 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASLLKLYLRELPEPVVPYAKYEDFL 230
Cdd:cd04376   10 PRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELYTAFI 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 231 SCATLLSKEEEAGVKELmkqVKSLPVVNYNLLKYICRFLDEV------------QSYSGvNKMSAQNLATVFGPNILR-- 296
Cdd:cd04376   90 GTALLEPDEQLEALQLL---IYLLPPCNCDTLHRLLKFLHTVaehaadsidedgQEVSG-NKMTSLNLATIFGPNLLHkq 165

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 170671704 297 ----PKVEDPLTIMEGTVVVQQLMSVMISKHDRLF 327
Cdd:cd04376  166 ksgeREFVQASLRIEESTAIINVVQTMIDNYEELF 200

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 170671704 129 GIFGQKLEDTVRYEkrygNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFD--SNTDVHTVA 206
Cdd:cd04383    1 KLFNGSLEEYIQDS----GQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADdqNDHDINSVA 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 207 SLLKLYLRELPEPVVPYAKYEDFLSCATLLSKEEEagVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNL 286
Cdd:cd04383   77 GVLKLYFRGLENPLFPKERFEDLMSCVKLENPTER--VHQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNL 154

                        170
                 ....*....|....*..
gi 170671704 287 ATVFGPNILR-PKVEDP 302
Cdd:cd04383  155 AICFGPTLMPvPEGQDQ 171

RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. 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 170671704 131 FGQKLEDTVRYEKRygnrlAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDS-NTDVHTVASLL 209
Cdd:cd04373    1 FGVPLANVVTSEKP-----IPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHNLDLVSkDFTVNAVAGAL 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 210 KLYLRELPEPVVPYAKYEDFLSCATLLSKEEEA-GVKELMKQvksLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLAT 288
Cdd:cd04373   76 KSFFSELPDPLIPYSMHLELVEAAKINDREQRLhALKELLKK---FPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSI 152

                        170       180       190
                 ....*....|....*....|....*....|..
gi 170671704 289 VFGPNILRPKVEDpLTIMEGTVVVQQLMSVMI 320
Cdd:cd04373  153 CFWPTLMRPDFTS-MEALSATRIYQTIIETFI 183

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 170671704 151 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKEL-----QDAFDCGEKPSFDSntdVHTVASLLKLYLRELPEPVVPYAK 225
Cdd:cd04385   16 PVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLleafrKDARSVQLREGEYT---VHDVADVLKRFLRDLPDPLLTSEL 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 226 YEDFLSCATLLSKEEeaGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNILRPKVEDPLTI 305
Cdd:cd04385   93 HAEWIEAAELENKDE--RIARYKELIRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLFQTDEHSVGQT 170

                        170
                 ....*....|
gi 170671704 306 MEGTVVVQQL 315
Cdd:cd04385  171 SHEVKVIEDL 180

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 170671704 151 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASLLKLYLRELPEPVVPYAKYEDFL 230
Cdd:cd04378   17 PFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLVELSELSPHDISSVLKLFLRQLPEPLILFRLYNDFI 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 231 SCATLLSKEEEAG---------------VKELMKQvksLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNIL 295
Cdd:cd04378   97 ALAKEIQRDTEEDkapntpievnriirkLKDLLRQ---LPASNYNTLQHLIAHLYRVAEQFEENKMSPNNLGIVFGPTLI 173

                 ....*.
gi 170671704 296 RPKVED 301
Cdd:cd04378  174 RPRPGD 179

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 131 FGQKLEDTVRYEKryGNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFD---CGEKPSFDSNTDVHTVAS 207
Cdd:cd04379    1 FGVPLSRLVEREG--ESRDVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFErnsAAVELSEELYPDINVITG 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 208 LLKLYLRELPEPVVPYAKYEDFLSCATLLSKEEEAGVKELMKQVKS-LPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNL 286
Cdd:cd04379   79 VLKDYLRELPEPLITPQLYEMVLEALAVALPNDVQTNTHLTLSIIDcLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNL 158

                        170
                 ....*....|....*
gi 170671704 287 ATVFGPNILRPKVED 301
Cdd:cd04379  159 AVCFGPVLMFCSQEF 173

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 170671704 130 IFGQKLEDTVRYEK-------------RYGNrlAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEK--P 194
Cdd:cd04396    1 VFGVSLEESLKYASvaisivdedgeqyVYGY--IPVVVAKCGVYLKENATEVEGIFRVAGSSKRIRELQLIFSTPPDygK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 195 SFD-SNTDVHTVASLLKLYLRELPEPVVPYAKYEDF---------------LSCATLLSKEEEAGVKELMKQVKSLPVVN 258
Cdd:cd04396   79 SFDwDGYTVHDAASVLRRYLNNLPEPLVPLDLYEEFrnplrkrprilqymkGRINEPLNTDIDQAIKEYRDLITRLPNLN 158

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 170671704 259 YNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNIL 295
Cdd:cd04396  159 RQLLLYLLDLLAVFARNSDKNLMTASNLAAIFQPGIL 195

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 170671704 152 MLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAF------DCGEKPSFDSNTDVHTVASLLKLYLRELPEPVVPYAK 225
Cdd:cd04374   30 KFVRKCIEAVETRGINEQGLYRVVGVNSKVQKLLSLGldpktsTPGDVDLDNSEWEIKTITSALKTYLRNLPEPLMTYEL 109

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 170671704 226 YEDFLSCATllSKEEEAGVKELMKQVKSLPVVNYNLLKYICRFLDEVQSYSGVNKMSAQNLATVFGPNILRPKVEDPLTI 305
Cdd:cd04374  110 HNDFINAAK--SENLESRVNAIHSLVHKLPEKNREMLELLIKHLTNVSDHSKKNLMTVSNLGVVFGPTLLRPQEETVAAI 187

                 ..
gi 170671704 306 ME 307
Cdd:cd04374  188 MD 189