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 261399911 117 VFGQRLDETVAYEQKFGPHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLL 196
Cdd:cd04390    2 VFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASLL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 197 KLYLRDLPEPVVPWSQYEGFLLCGQLTNADEAKAQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATV 276
Cdd:cd04390   82 KLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATV 161

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 261399911 277 IGVNLIRSKVEDPAVIMRGTPQIQRVMTMMIRDHEVLF 314
Cdd:cd04390  162 FGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

DNA double-strand break repair ATPase Rad50;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 505 NSGEEEIDSLQRMVQELRKEIETQKQMYEEqIKNLEKENYDVWAKVvrlneelekekkksAALEISLRNMERSREDVEKR 584
Cdd:PRK03918 210 NEISSELPELREELEKLEKEVKELEELKEE-IEELEKELESLEGSK--------------RKLEEKIRELEERIEELKKE 274

                         90       100
                 ....*....|....*....|.
gi 261399911 585 NKALEEEVKEfVKSMKEPKTE 605
Cdd:PRK03918 275 IEELEEKVKE-LKELKEKAEE 294

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 261399911 117 VFGQRLDETVAYEQKFGPHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLL 196
Cdd:cd04390    2 VFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASLL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 197 KLYLRDLPEPVVPWSQYEGFLLCGQLTNADEAKAQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATV 276
Cdd:cd04390   82 KLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATV 161

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 261399911 277 IGVNLIRSKVEDPAVIMRGTPQIQRVMTMMIRDHEVLF 314
Cdd:cd04390  162 FGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911  138 PILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFD-RDTDVHTVASLLKLYLRDLPEPVVPWSQYEGF 216
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDlEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 261399911  217 LLCGQLTNADEakaQQELMKQL-SILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKV 286
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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 261399911    47 PIKMGWLKKQ-RSIVKNWQQRYFVLRAQQLYYYKDEE---DTKPQGCMYLPGCTIKEIATNPEEAGKFVFEII 115
Cdd:smart00233   1 VIKEGWLYKKsGGGKKSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIK 73

DNA double-strand break repair ATPase Rad50;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 505 NSGEEEIDSLQRMVQELRKEIETQKQMYEEqIKNLEKENYDVWAKVvrlneelekekkksAALEISLRNMERSREDVEKR 584
Cdd:PRK03918 210 NEISSELPELREELEKLEKEVKELEELKEE-IEELEKELESLEGSK--------------RKLEEKIRELEERIEELKKE 274

                         90       100
                 ....*....|....*....|.
gi 261399911 585 NKALEEEVKEfVKSMKEPKTE 605
Cdd:PRK03918 275 IEELEEKVKE-LKELKEKAEE 294

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 492 LASPNSETGPGKKNSGEEEIDSLQRMVQELRKEIETQKQmyeeQIKNLEKENYDVWAKVVRLNEELEKEKKKSAALEISL 571
Cdd:COG4942   10 LLALAAAAQADAAAEAEAELEQLQQEIAELEKELAALKK----EEKALLKQLAALERRIAALARRIRALEQELAALEAEL 85

                         90       100
                 ....*....|....*....|....*...
gi 261399911 572 RNMERSREDVEKRNKALEEEVKEFVKSM 599
Cdd:COG4942   86 AELEKEIAELRAELEAQKEELAELLRAL 113

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 261399911 117 VFGQRLDETVAYEQKFGPHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLL 196
Cdd:cd04390    2 VFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASLL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 197 KLYLRDLPEPVVPWSQYEGFLLCGQLTNADEAKAQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATV 276
Cdd:cd04390   82 KLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLATV 161

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 261399911 277 IGVNLIRSKVEDPAVIMRGTPQIQRVMTMMIRDHEVLF 314
Cdd:cd04390  162 FGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. The RhoGAPs are one of the major classes of regulators of Rho G proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 138 PILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQYEGFL 217
Cdd:cd00159    1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDRGEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYDEFI 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 218 LCgqLTNADEAKAQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKVEDPAVIMRgTP 297
Cdd:cd00159   81 EL--AKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLED-IK 157

                        170
                 ....*....|..
gi 261399911 298 QIQRVMTMMIRD 309
Cdd:cd00159  158 KLNEIVEFLIEN 169

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 261399911  45 ERPIKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIPVFGQ 120
Cdd:cd13263    1 ERPIKSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDTKPQGTIPLPGNKVKEVPFNPEEPGKFLFEIIPGGGG 76

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 261399911 116 PVFGQRLDEtvayeqkfgpHL------VPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAG--ERPSFDRDT 187
Cdd:cd04386    3 PVFGTPLEE----------HLkrtgreIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGtfSLPLDEFYS 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 188 DVHTVASLLKLYLRDLPEPVVPWSQYEGFLLCGQLTnaDEAKAQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNK 267
Cdd:cd04386   73 DPHAVASALKSYLRELPDPLLTYNLYEDWVQAANKP--DEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENK 150

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 261399911 268 MSVDNLATVIGVNLIRSKVEDPAVIMRGTPQIQRVMT--MMIRDHEVLFP 315
Cdd:cd04386  151 MSPSNIAIVLAPNLLWAKNEGSLAEMAAGTSVHVVAIveLIISHADWFFP 200

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 261399911 137 VPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQYEGF 216
Cdd:cd04376    9 VPRLVESCCQHLEKHGLQTVGIFRVGSSKKRVRQLREEFDRGIDVVLDENHSVHDVAALLKEFFRDMPDPLLPRELYTAF 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 217 LLCGQLTNADEAKAQQELmkqLSILPRDNYSLLSYICRFLHEIQLNCAV-----------NKMSVDNLATVIGVNLIR-- 283
Cdd:cd04376   89 IGTALLEPDEQLEALQLL---IYLLPPCNCDTLHRLLKFLHTVAEHAADsidedgqevsgNKMTSLNLATIFGPNLLHkq 165

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 261399911 284 ----SKVEDPAVIMRGTPQIQRVMTMMIRDHEVLFPKSKDI 320
Cdd:cd04376  166 ksgeREFVQASLRIEESTAIINVVQTMIDNYEELFMVSPEL 206

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 261399911 133 GPHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQ 212
Cdd:cd04404   19 EQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYEDVHLPAVILKTFLRELPEPLLTFDL 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 213 YEGFLLCGQLTNADEAKAQQELMKQlsiLPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKveDPAVI 292
Cdd:cd04404   99 YDDIVGFLNVDKEERVERVKQLLQT---LPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLWAK--DASMS 173

                        170       180
                 ....*....|....*....|..
gi 261399911 293 MRGTPQIQRVMTMMIRDHEVLF 314
Cdd:cd04404  174 LSAINPINTFTKFLLDHQDEIF 195

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 261399911 117 VFGQRLDET-VAYEQKFgphlVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAG--ERPSFD-RDTDVHTV 192
Cdd:cd04395    1 TFGVPLDDCpPSSENPY----VPLIVEVCCNIVEARGLETVGIYRVPGNNAAISALQEELNRGgfDIDLQDpRWRDVNVV 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 193 ASLLKLYLRDLPEPVVPWSQYEGFLLCGQLTNADEAkaQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDN 272
Cdd:cd04395   77 SSLLKSFFRKLPEPLFTNELYPDFIEANRIEDPVER--LKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRN 154

                        170
                 ....*....|..
gi 261399911 273 LATVIGVNLIRS 284
Cdd:cd04395  155 LAIVFGPTLVRT 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 261399911 118 FGQRLDETVAYEQKFGPHL-VPILVEKCAEFILE-HGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDtDVHTVASL 195
Cdd:cd04389    1 FGSSLEEIMDRQKEKYPELkLPWILTFLSEKVLAlGGFQTEGIFRVPGDIDEVNELKLRVDQWDYPLSGLE-DPHVPASL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 196 LKLYLRDLPEPVVPWSQYEGfllCgqLTNADEAKAQQELMKQLSILprdNYSLLSYICRFLHE--IQLNCAVNKMSVDNL 273
Cdd:cd04389   80 LKLWLRELEEPLIPDALYQQ---C--ISASEDPDKAVEIVQKLPII---NRLVLCYLINFLQVfaQPENVAHTKMDVSNL 151

                        170       180       190
                 ....*....|....*....|....*....|....
gi 261399911 274 ATVIGVNLIRSKVEDPAVIMRGTPQIQRVMTMMI 307
Cdd:cd04389  152 AMVFAPNILRCTSDDPRVIFENTRKEMSFLRTLI 185

Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ARHGAP24, p73RhoGAp, and Filamin-A-associated RhoGAP) 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. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 261399911  48 IKMGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDTKPQGCMYLPGCTIKEIATNPEEAGKFVFEIIP 116
Cdd:cd13379    4 IKCGWLRKQGGFVKTWHTRWFVLKGDQLYYFKDEDETKPLGTIFLPGNRVTEHPCNEEEPGKFLFEVVP 72

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 261399911 137 VPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERP-SFDRDTD-VHTVASLLKLYLRDLPEPVVPWSQYE 214
Cdd:cd04385   15 IPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSvQLREGEYtVHDVADVLKRFLRDLPDPLLTSELHA 94

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 261399911 215 GFLLCGQLTNADEA-KAQQELmkqLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNL 281
Cdd:cd04385   95 EWIEAAELENKDERiARYKEL---IRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTL 159

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 261399911 118 FGQRLDETVayeqKFGPHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFD--RDTDVHTVASL 195
Cdd:cd04383    3 FNGSLEEYI----QDSGQAIPLVVESCIRFINLYGLQHQGIFRVSGSQVEVNDIKNAFERGEDPLADdqNDHDINSVAGV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 196 LKLYLRDLPEPVVPWSQYEGFLLCGQLTNADEaKAQQeLMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLAT 275
Cdd:cd04383   79 LKLYFRGLENPLFPKERFEDLMSCVKLENPTE-RVHQ-IREILSTLPRSVIIVMRYLFAFLNHLSQFSDENMMDPYNLAI 156

                 ....*...
gi 261399911 276 VIGVNLIR 283
Cdd:cd04383  157 CFGPTLMP 164

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 261399911 136 LVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERP--SFDRDTDVHTVASLLKLYLRDLPEPVVPWSQY 213
Cdd:cd04387   15 KVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDvsVMLSEMDVNAIAGTLKLYFRELPEPLFTDELY 94

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 261399911 214 EGFLlcGQLTNADEAKAQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKVED 288
Cdd:cd04387   95 PNFA--EGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKE 167

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 261399911 118 FGQRLDETVAYEQKFGPHLVPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDrDTDVHTVASLLK 197
Cdd:cd04381    1 FGASLSLAVERSRCHDGIDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRESPNLE-EYEPPTVASLLK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 198 LYLRDLPEPVVP---WSQYEGflLCGQLTnadEAKAQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLA 274
Cdd:cd04381   80 QYLRELPEPLLTkelMPRFEE--ACGRPT---EAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNIS 154

                 ...
gi 261399911 275 TVI 277
Cdd:cd04381  155 IVL 157

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 261399911 137 VPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQYEGF 216
Cdd:cd04407   15 VPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLENYPIHAITGLLKQWLRELPEPLMTFAQYNDF 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 217 LLCGQLTNADEakAQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIR-SKVEDPAVIMRG 295
Cdd:cd04407   95 LRAVELPEKQE--QLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRcPDSSDPLTSMKD 172

                        170
                 ....*....|....
gi 261399911 296 TPQIQRVMTMMIRD 309
Cdd:cd04407  173 VAKTTTCVEMLIKE 186

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 261399911 137 VPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAGERPSFD-RDTDVHTVASLLKLYLRDLPEPVVPWSQYEG 215
Cdd:cd04373   15 IPIFLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQKQFDQDHNLDLVsKDFTVNAVAGALKSFFSELPDPLIPYSMHLE 94

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 261399911 216 FLLCGQLTnaDEAKAQQELMKQLSILPRDNYSLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIR 283
Cdd:cd04373   95 LVEAAKIN--DREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMR 160

RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 is unknown. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 117 VFGQRLDETVAYEQKFGPHL-VPILVEKCAEFILEHGRNEEGIFRLPGQDNLVKQLRDAFDAgerPSFDRDTD-----VH 190
Cdd:cd04391    1 LFGVPLSTLLERDQKKVPGSkVPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEA---KFYEGTFLwdqvkQH 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261399911 191 TVASLLKLYLRDLPEPVVPWSQYEGFLLCGQL-TNADEAKAQQELMKQLSILPRDNYSLLsyiCRFLHEIQLNCAVNKMS 269
Cdd:cd04391   78 DAASLLKLFIRELPQPLLTVEYLPAFYSVQGLpSKKDQLQALNLLVLLLPEANRDTLKAL---LEFLQKVVDHEEKNKMN 154

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 261399911 270 VDNLATVIGVNL-----IRSK-VEDPAVIMRGTPQIQRVMTMMIRDHEVLF 314
Cdd:cd04391  155 LWNVAMIMAPNLfpprgKHSKdNESLQEEVNMAAGCANIMRLLIRYQDLLW 205