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 1201884024 131 GIFGQKLEDTVRYEKRYGNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASL 210
Cdd:cd04390     1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 211 LKLYLRELPEPVIPYAKYEDFLSCAKMLSKEEEMGLTELVKQVKSLPAVNYNLLKYICRFLDEVQSYSGINKMSVQNLAT 290
Cdd:cd04390    81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1201884024 291 VFGPNILRPKVEDPLTIMEGTVVVQQLMSVMISKHEELF 329
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 1201884024 650 KQEMAKQKLEYETRIKSLEQrnltlETEMiALHEELDQERKKFTMVEiKMRNAERAKEDAEKRNDMLQKEMEQF 723
Cdd:pfam20492   1 REEAEREKQELEERLKQYEE-----ETKK-AQEELEESEETAEELEE-ERRQAEEEAERLEQKRQEAEEEKERL 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 1201884024 131 GIFGQKLEDTVRYEKRYGNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASL 210
Cdd:cd04390     1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 211 LKLYLRELPEPVIPYAKYEDFLSCAKMLSKEEEMGLTELVKQVKSLPAVNYNLLKYICRFLDEVQSYSGINKMSVQNLAT 290
Cdd:cd04390    81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1201884024 291 VFGPNILRPKVEDPLTIMEGTVVVQQLMSVMISKHEELF 329
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 1201884024 153 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFD-SNTDVHTVASLLKLYLRELPEPVIPYAKYEDF 231
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDlEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 232 LSCAKMLSKEEemGLTELVKQVKSLPAVNYNLLKYICRFLDEVQSYSGINKMSVQNLATVFGPNILRPKV 301
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 1201884024   20 TIKCGWLRKQG-GFVKTWHTRWFVLKGDQLYYFKDEDE---IKPLGAIFLPGNRVIEHPCNEESPGKFLFEVVpggdrer 95
Cdd:smart00233   1 VIKEGWLYKKSgGGKKSWKKRYFVLFNSTLLYYKSKKDkksYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIK------- 73

                           90       100
                   ....*....|....*....|....*....
gi 1201884024   96 mTANHETYLLMASTQNDMEDWVKSIRRVI 124
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 1201884024 650 KQEMAKQKLEYETRIKSLEQrnltlETEMiALHEELDQERKKFTMVEiKMRNAERAKEDAEKRNDMLQKEMEQF 723
Cdd:pfam20492   1 REEAEREKQELEERLKQYEE-----ETKK-AQEELEESEETAEELEE-ERRQAEEEAERLEQKRQEAEEEKERL 67

Domain of unknown function (DUF4670); This family of proteins is found in eukaryotes. Proteins in this family are typically between 373 and 763 amino acids in length.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 559 EISLPEHSNSCRSstttcpEQDFFVGNF-EDSVLDGPPQEDLSNTGDYENKSDRRS-------VGGH--SSRATSSSDNS 628
Cdd:pfam15709 248 ELSGPDVINSKET------EDASERGAFsSDSVVEDPWLSSKYDAEESQVSIDGRSsptqtfvVTGNmeSEEERSEEDPS 321

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 629 ETFIANSTNNHSALhslvSSLKQEMAKQK-LEYE-TRIKSLEQRNLTLETEMIA--LHEELDQERKKFTMvEIKMRNA-- 702
Cdd:pfam15709 322 KALLEKREQEKASR----DRLRAERAEMRrLEVErKRREQEEQRRLQQEQLERAekMREELELEQQRRFE-EIRLRKQrl 396

                         170       180
                  ....*....|....*....|..
gi 1201884024 703 --ERAKEDAEKRNDMLQKEMEQ 722
Cdd:pfam15709 397 eeERQRQEEEERKQRLQLQAAQ 418

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 1201884024 131 GIFGQKLEDTVRYEKRYGNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASL 210
Cdd:cd04390     1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 211 LKLYLRELPEPVIPYAKYEDFLSCAKMLSKEEEMGLTELVKQVKSLPAVNYNLLKYICRFLDEVQSYSGINKMSVQNLAT 290
Cdd:cd04390    81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1201884024 291 VFGPNILRPKVEDPLTIMEGTVVVQQLMSVMISKHEELF 329
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 1201884024  21 IKCGWLRKQGGFVKTWHTRWFVLKGDQLYYFKDEDEIKPLGAIFLPGNRVIEHPCNEESPGKFLFEVVPGGDRERMTANH 100
Cdd:cd13263     4 IKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGGDRMTSNH 83

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1201884024 101 ETYLLMASTQNDMEDWVKSIRRVIWAPFGGG 131
Cdd:cd13263    84 DSYLLMANSQAEMEEWVKVIRRVIGSPFGGG 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 153 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFD-SNTDVHTVASLLKLYLRELPEPVIPYAKYEDF 231
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDlEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 232 LSCAKMLSKEEemGLTELVKQVKSLPAVNYNLLKYICRFLDEVQSYSGINKMSVQNLATVFGPNILRPKV 301
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 1201884024  19 GTIKCGWLRKQGGFVKTWHTRWFVLKGDQLYYFKDEDEIKPLGAIFLPGNRVIEHPCNEESPGKFLFEVVPGG--DRERM 96
Cdd:cd13378     2 GVLKAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDEEETKPQGCISLQGSQVNELPPNPEEPGKHLFEILPGGagDREKV 81

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1201884024  97 TANHETYLLMASTQNDMEDWVKSIRRVIWAPFGGG 131
Cdd:cd13378    82 PMNHEAFLLMANSQSDMEDWVKAIRRVIWAPFGGG 116

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 1201884024 132 IFGQKLEDTVryeKRYGNRLApMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCG--EKPSFDSNTDVHTVAS 209
Cdd:cd04386     4 VFGTPLEEHL---KRTGREIA-LPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGtfSLPLDEFYSDPHAVAS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 210 LLKLYLRELPEPVIPYAKYEDFLSCAKMLSKEEEmgLTELVKQVKSLPAVNYNLLKYICRFLDEVQSYSGINKMSVQNLA 289
Cdd:cd04386    80 ALKSYLRELPDPLLTYNLYEDWVQAANKPDEDER--LQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENKMSPSNIA 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1201884024 290 TVFGPNILRPKVEDPLTIME--GTVVVQQLMSVMISKHEELFPKDA 333
Cdd:cd04386   158 IVLAPNLLWAKNEGSLAEMAagTSVHVVAIVELIISHADWFFPGEV 203

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 1201884024 149 NRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCG--EKPSFDSN-TDVHTVASLLKLYLRELPEPVIPY 225
Cdd:cd04395    15 NPYVPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGgfDIDLQDPRwRDVNVVSSLLKSFFRKLPEPLFTN 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 226 AKYEDFLSCAKMLSKEEEMglTELVKQVKSLPAVNYNLLKYICRFLDEVQSYSGINKMSVQNLATVFGPNILRPKvEDPL 305
Cdd:cd04395    95 ELYPDFIEANRIEDPVERL--KELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTS-DDNM 171

                  ...
gi 1201884024 306 TIM 308
Cdd:cd04395   172 ETM 174

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 1201884024 153 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASLLKLYLRELPEPVIPYAKYEDFL 232
Cdd:cd04382    18 PALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNLSKVDIHVICGCLKDFLRSLKEPLITFALWKEFM 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 233 SCAKMLSkeEEMGLTELVKQVKSLPAVNYNLLKYICRFLDEVqSYSGINKMSVQNLATVFGPNILRPKVEDP--LTIMEG 310
Cdd:cd04382    98 EAAEILD--EDNSRAALYQAISELPQPNRDTLAFLILHLQRV-AQSPECKMDINNLARVFGPTIVGYSVPNPdpMTILQD 174

                         170
                  ....*....|...
gi 1201884024 311 TVVVQQLMSVMIS 323
Cdd:cd04382   175 TVRQPRVVERLLE 187

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 1201884024 132 IFGQKLEDTVRYE-KRYGNRLAPMLVEQCVDFI-RQRGLKEEGLFRLPGQANLVKELQDAFDC-GEKPSFDSNT--DVHT 206
Cdd:cd04400     1 IFGSPLEEAVELSsHKYNGRDLPSVVYRCIEYLdKNRAIYEEGIFRLSGSASVIKQLKERFNTeYDVDLFSSSLypDVHT 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 207 VASLLKLYLRELPEPVIPYAKYEDFLSCAKMLSKEEEMGLtELVKQVKSLPAVNYNLLKYICRFLDEVQSYSGINKMSVQ 286
Cdd:cd04400    81 VAGLLKLYLRELPTLILGGELHNDFKRLVEENHDRSQRAL-ELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNKMNLR 159

                         170
                  ....*....|..
gi 1201884024 287 NLATVFGP--NI 296
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 1201884024 153 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASLLKLYLRELPEPVIPYAKYEDFL 232
Cdd:cd04376    10 PRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELYTAFI 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 233 SCAKmLSKEEEMGLTELVKQVksLPAVNYNLLKYICRFLDEV------------QSYSGiNKMSVQNLATVFGPNILR-- 298
Cdd:cd04376    90 GTAL-LEPDEQLEALQLLIYL--LPPCNCDTLHRLLKFLHTVaehaadsidedgQEVSG-NKMTSLNLATIFGPNLLHkq 165

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1201884024 299 ----PKVEDPLTIMEGTVVVQQLMSVMISKHEELF 329
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 1201884024 131 GIFGQKLEDTVRYEkrygNRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFD--SNTDVHTVA 208
Cdd:cd04383     1 KLFNGSLEEYIQDS----GQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADdqNDHDINSVA 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 209 SLLKLYLRELPEPVIPYAKYEDFLSCAKMLSKEEEMglTELVKQVKSLPAVNYNLLKYICRFLDEVQSYSGINKMSVQNL 288
Cdd:cd04383    77 GVLKLYFRGLENPLFPKERFEDLMSCVKLENPTERV--HQIREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNL 154

                         170
                  ....*....|....*..
gi 1201884024 289 ATVFGPNILR-PKVEDP 304
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 1201884024 133 FGQKLEDTVRYEKRYgnrlaPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDS-NTDVHTVASLL 211
Cdd:cd04373     1 FGVPLANVVTSEKPI-----PIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHNLDLVSkDFTVNAVAGAL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 212 KLYLRELPEPVIPYAKYEDFLSCAKMLSKEEEM-GLTELVKQvksLPAVNYNLLKYICRFLDEVQSYSGINKMSVQNLAT 290
Cdd:cd04373    76 KSFFSELPDPLIPYSMHLELVEAAKINDREQRLhALKELLKK---FPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSI 152

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1201884024 291 VFGPNILRPKVEDpLTIMEGTVVVQQLMSVMI 322
Cdd:cd04373   153 CFWPTLMRPDFTS-MEALSATRIYQTIIETFI 183

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 149 NRLAPMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASLLKLYLRELPEPVIPYAKY 228
Cdd:cd04377    12 DRSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSVNLEDYPIHVITSVLKQWLRELPEPLMTFELY 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 229 EDFLSCAKMLSKEEEM-GLTELVKQvksLPAVNYNLLKYICRFLDEVQSYSGINKMSVQNLATVFGPNILR-PKVEDPLT 306
Cdd:cd04377    92 ENFLRAMELEEKQERVrALYSVLEQ---LPRANLNTLERLIFHLVRVALQEEVNRMSANALAIVFAPCILRcPDTADPLQ 168

                  ...
gi 1201884024 307 IME 309
Cdd:cd04377   169 SLQ 171

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 1201884024 153 PMLVEQCVDFIRQRGLKEEGLFRLPGQANLVKELQDAFDCGEKPSFDSNTDVHTVASLLKLYLRELPEPVIPYAKYEDFL 232
Cdd:cd04378    17 PFIIKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAFENGKDLVELSELSPHDISSVLKLFLRQLPEPLILFRLYNDFI 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 233 SCAKMLSKEEEMG--------LTELVKQVKSL----PAVNYNLLKYICRFLDEVQSYSGINKMSVQNLATVFGPNILRPK 300
Cdd:cd04378    97 ALAKEIQRDTEEDkapntpieVNRIIRKLKDLlrqlPASNYNTLQHLIAHLYRVAEQFEENKMSPNNLGIVFGPTLIRPR 176

                  ...
gi 1201884024 301 VED 303
Cdd:cd04378   177 PGD 179

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 1201884024 132 IFGQKLEDtvrYEKRYGNRLaPMLVEQCVDFIRQRGLKEeGLFRLPGQANLVKELQDAFDCGEKP---SFDSNTDVHTVA 208
Cdd:cd04384     2 VFGCDLTE---HLLNSGQDV-PQVLKSCTEFIEKHGIVD-GIYRLSGIASNIQRLRHEFDSEQIPdltKDVYIQDIHSVS 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1201884024 209 SLLKLYLRELPEPVIPYAKYEDFLSCAKMLSKEEEMGLTELVkqVKSLPAVNYNLLKYICRFLDEVQSYSGINKMSVQNL 288
Cdd:cd04384    77 SLCKLYFRELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDV--IQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNL 154

                         170
                  ....*....|..
gi 1201884024 289 ATVFGPNILRPK 300
Cdd:cd04384   155 AIVWAPNLLRSK 166

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 1201884024 147 YGNrLAPMLVEQCvDFIRQRgLKEEGLFRLPGQANLVKELQDAFDCGEkpSFDSNTDVHTVASLLKLYLRELPEPVIPYA 226
Cdd:cd04394    17 YGN-VPKFLVDAC-TFLLDH-LSTEGLFRKSGSVVRQKELKAKLEGGE--ACLSSALPCDVAGLLKQFFRELPEPLLPYD 91

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1201884024 227 KYEDFLSCAKMLSKEEEMGLTELVKQVksLPAVNYNLLKYICRFLDEVQSYSGINKMSVQNLATVFGPNIL 297
Cdd:cd04394    92 LHEALLKAQELPTDEERKSATLLLTCL--LPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLF 160