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 83582813 130 AVFGQRLDETVAYEQKFGPHLVPILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASL 209
Cdd:cd04390   1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 210 LKLYLRDLPEPVVPWSQYEGFLLCGQLMNADEAKAQQELVKQLSTLPRDNYNLLSYICRFLHEIQLNCAVNKMSVDNLAT 289
Cdd:cd04390  81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 83582813 290 VIGVNLIRSKVEDPAVIMRGTPQIQRVMTMMIRDHEVLF 328
Cdd:cd04390 161 VFGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813    519 NSGEDDLDSLQRTVQSLQKEIETQKQV---YEEQIKNLEKENYDVWAKVVRLNEELERERKKFAALEISLRNVERSREDV 595
Cdd:TIGR02169  815 REIEQKLNRLTLEKEYLEKEIQELQEQridLKEQIKSIEKEIENLNGKKEELEEELEELEAALRDLESRLGDLKKERDEL 894

                           90       100
                   ....*....|....*....|..
gi 83582813    596 EKRNRVLEEEVKEFVKSMEKPK 617
Cdd:TIGR02169  895 EAQLRELERKIEELEAQIEKKR 916

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 83582813 130 AVFGQRLDETVAYEQKFGPHLVPILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASL 209
Cdd:cd04390   1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 210 LKLYLRDLPEPVVPWSQYEGFLLCGQLMNADEAKAQQELVKQLSTLPRDNYNLLSYICRFLHEIQLNCAVNKMSVDNLAT 289
Cdd:cd04390  81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 83582813 290 VIGVNLIRSKVEDPAVIMRGTPQIQRVMTMMIRDHEVLF 328
Cdd:cd04390 161 VFGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813    151 VPILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDAGERPSFD-RDTDVHTVASLLKLYLRDLPEPVVPWSQYEG 229
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDlSEYDVHDVAGLLKLFLRELPEPLITYELYEE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813    230 FLLCGQLMNADEAKaqQELVKQLSTLPRDNYNLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKVEDPAVIMrG 309
Cdd:smart00324  83 FIEAAKLEDETERL--RALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLK-D 159

                          170
                   ....*....|....*
gi 83582813    310 TPQIQRVMTMMIRDH 324
Cdd:smart00324 160 IRHQNTVIEFLIENA 174

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 83582813     21 PIKVGWLKKQ-RSIVKNWQQRYFVLRAQQLYYYKDEE---DSKPQGCMYLPGSTVKEIATNPEEAGKFVFEVIPASsdqn 96
Cdd:smart00233   1 VIKEGWLYKKsGGGKKSWKKRYFVLFNSTLLYYKSKKdkkSYKPKGSIDLSGCTVREAPDPDSSKKPHCFEIKTSD---- 76

                           90       100
                   ....*....|....*....|....*...
gi 83582813     97 rigQDSYVLMASSQVEMEEWVKFLRRVA 124
Cdd:smart00233  77 ---RKTLLLQAESEEEREKWVEALRKAI 101

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813    519 NSGEDDLDSLQRTVQSLQKEIETQKQV---YEEQIKNLEKENYDVWAKVVRLNEELERERKKFAALEISLRNVERSREDV 595
Cdd:TIGR02169  815 REIEQKLNRLTLEKEYLEKEIQELQEQridLKEQIKSIEKEIENLNGKKEELEEELEELEAALRDLESRLGDLKKERDEL 894

                           90       100
                   ....*....|....*....|..
gi 83582813    596 EKRNRVLEEEVKEFVKSMEKPK 617
Cdd:TIGR02169  895 EAQLRELERKIEELEAQIEKKR 916

Septation ring formation regulator, EzrA; During the bacterial cell cycle, the tubulin-like cell-division protein FtsZ polymerizes into a ring structure that establishes the location of the nascent division site. EzrA modulates the frequency and position of FtsZ ring formation. The structure contains 5 spectrin like alpha helical repeats.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813   511 SEMEAGSKNSGEDDLDSLQRTVQSLQKEIETQKQVY----------EEQIKNLEKENYDVWAKVVRLNEELERERKKFAA 580
Cdd:pfam06160 324 NENELERVRGLEKQLEELEKRYDEIVERLEEKEVAYselqeeleeiLEQLEEIEEEQEEFKESLQSLRKDELEAREKLDE 403

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 83582813   581 LEISLRNVERSredVEKRN------------RVLEEEVKEFVKSMEKPK 617
Cdd:pfam06160 404 FKLELREIKRL---VEKSNlpglpesyldyfFDVSDEIEDLADELNEVP 449

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 83582813 130 AVFGQRLDETVAYEQKFGPHLVPILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASL 209
Cdd:cd04390   1 GVFGQRLEDTVAYERKFGPRLVPILVEQCVDFIREHGLKEEGLFRLPGQANLVKQLQDAFDAGERPSFDSDTDVHTVASL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 210 LKLYLRDLPEPVVPWSQYEGFLLCGQLMNADEAKAQQELVKQLSTLPRDNYNLLSYICRFLHEIQLNCAVNKMSVDNLAT 289
Cdd:cd04390  81 LKLYLRELPEPVIPWAQYEDFLSCAQLLSKDEEKGLGELMKQVSILPKVNYNLLSYICRFLDEVQSNSSVNKMSVQNLAT 160

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 83582813 290 VIGVNLIRSKVEDPAVIMRGTPQIQRVMTMMIRDHEVLF 328
Cdd:cd04390 161 VFGPNILRPKVEDPATIMEGTPQIQQLMTVMISKHEPLF 199

GTPase-activator protein for Rho-like GTPases; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases. etter domain limits and outliers.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813    151 VPILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDAGERPSFD-RDTDVHTVASLLKLYLRDLPEPVVPWSQYEG 229
Cdd:smart00324   3 IPIIVEKCIEYLEKRGLDTEGIYRVSGSKSRVKELRDAFDSGPDPDLDlSEYDVHDVAGLLKLFLRELPEPLITYELYEE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813    230 FLLCGQLMNADEAKaqQELVKQLSTLPRDNYNLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKVEDPAVIMrG 309
Cdd:smart00324  83 FIEAAKLEDETERL--RALRELLSLLPPANRATLRYLLAHLNRVAEHSEENKMTARNLAIVFGPTLLRPPDGEVASLK-D 159

                          170
                   ....*....|....*
gi 83582813    310 TPQIQRVMTMMIRDH 324
Cdd:smart00324 160 IRHQNTVIEFLIENA 174

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813   152 PILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDAGERPSFD-RDTDVHTVASLLKLYLRDLPEPVVPWSQYEGF 230
Cdd:pfam00620   1 PLIVRKCVEYLEKRGLDTEGIFRVSGSASRIKELREAFDRGPDVDLDlEEEDVHVVASLLKLFLRELPEPLLTFELYEEF 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813   231 LLCGQLMNADEAKaqQELVKQLSTLPRDNYNLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKV 300
Cdd:pfam00620  81 IEAAKLPDEEERL--EALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLRPPD 148

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813  22 IKVGWLKKQRSIVKNWQQRYFVLRAQQLYYYKDEEDSKPQGCMYLPGSTVKEIATNPEEAGKFVFEVIPAsSDQNRI--G 99
Cdd:cd13379   4 IKCGWLRKQGGFVKTWHTRWFVLKGDQLYYFKDEDETKPLGTIFLPGNRVTEHPCNEEEPGKFLFEVVPG-GDRERMtaN 82

                        90       100       110
                ....*....|....*....|....*....|.
gi 83582813 100 QDSYVLMASSQVEMEEWVKFLRRVAGTPSGA 130
Cdd:cd13379  83 HETYLLMASTQNDMEDWVKSIRRVIWAPFGG 113

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 83582813 131 VFGQRLDEtvayeqkfgpHL------VPILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDAG--ERPSFDRDTD 202
Cdd:cd04386   4 VFGTPLEE----------HLkrtgreIALPIEACVMCLLETGMNEEGLFRVGGGASKLKRLKAALDAGtfSLPLDEFYSD 73

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 203 VHTVASLLKLYLRDLPEPVVPWSQYEGFLlcgQLMN-ADEAKAQQELVKQLSTLPRDNYNLLSYICRFLHEIQLNCAVNK 281
Cdd:cd04386  74 PHAVASALKSYLRELPDPLLTYNLYEDWV---QAANkPDEDERLQAIWRILNKLPRENRDNLRYLIKFLSKLAQKSDENK 150

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 83582813 282 MSVDNLATVIGVNLIRSKVEDPAVIMRGTPQIQRVMT--MMIRDHEVLFP 329
Cdd:cd04386 151 MSPSNIAIVLAPNLLWAKNEGSLAEMAAGTSVHVVAIveLIISHADWFFP 200

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 83582813 147 GPHLVPILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQ 226
Cdd:cd04404  19 EQEPIPPVVRETVEYLQAHALTTEGIFRRSANTQVVKEVQQKYNMGEPVDFDQYEDVHLPAVILKTFLRELPEPLLTFDL 98

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 227 YEGFLLCGQLMNADEAKAQQELVKqlsTLPRDNYNLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKveDPAVI 306
Cdd:cd04404  99 YDDIVGFLNVDKEERVERVKQLLQ---TLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLWAK--DASMS 173

                       170       180
                ....*....|....*....|..
gi 83582813 307 MRGTPQIQRVMTMMIRDHEVLF 328
Cdd:cd04404 174 LSAINPINTFTKFLLDHQDEIF 195

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 83582813 131 VFGQRLDETVAYE-QKFGPHLVPILVEKCAEFILEHG-VSEEGIFRLPGQDNLVKQLRDAFDAGerpsFDRDT------- 201
Cdd:cd04400   1 IFGSPLEEAVELSsHKYNGRDLPSVVYRCIEYLDKNRaIYEEGIFRLSGSASVIKQLKERFNTE----YDVDLfssslyp 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 202 DVHTVASLLKLYLRDLPEPVVPWSQYEGFLLCGQLmNADEAKAQQELVKQLSTLPRDNYNLLSYICRFLHEIQLNCAVNK 281
Cdd:cd04400  77 DVHTVAGLLKLYLRELPTLILGGELHNDFKRLVEE-NHDRSQRALELKDLVSQLPQANYDLLYVLFSFLRKIIEHSDVNK 155

                ....*....
gi 83582813 282 MSVDNLATV 290
Cdd:cd04400 156 MNLRNVCIV 164

RhoGAP_chimaerin: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of chimaerins. Chimaerins are a family of phorbolester- and diacylglycerol-responsive GAPs specific for the Rho-like GTPase Rac. Chimaerins exist in two alternative splice forms that each contain a C-terminal GAP domain, and a central C1 domain which binds phorbol esters, inducing a conformational change that activates the protein; one splice form is lacking the N-terminal Src homology-2 (SH2) domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 148 PHLVPILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDA-GERPSFDRDT--DVHTVASLLKLYLRDLPEPVVPW 224
Cdd:cd04372  13 NTQRPMVVDMCIREIEARGLQSEGLYRVSGFAEEIEDVKMAFDRdGEKADISATVypDINVITGALKLYFRDLPIPVITY 92

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 225 SQYEGFLLCGQLMNADEakaQQELVKQ-LSTLPRDNYNLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKVEDP 303
Cdd:cd04372  93 DTYPKFIDAAKISNPDE---RLEAVHEaLMLLPPAHYETLRYLMEHLKRVTLHEKDNKMNAENLGIVFGPTLMRPPEDSA 169

                       170       180
                ....*....|....*....|....*.
gi 83582813 304 AVIMRG-TPQIQrVMTMMIRDHEVLF 328
Cdd:cd04372 170 LTTLNDmRYQIL-IVQLLITNEDVLF 194

RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in MgcRacGAP proteins. MgcRacGAP plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling. ii) after phosphorylation by aurora B MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain a N-terminal C1-like domain, and a C-terminal RhoGAP domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 148 PHLVPILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQY 227
Cdd:cd04382  14 SPMIPALIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNLSKVDIHVICGCLKDFLRSLKEPLITFALW 93

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 228 EGFLLCGQlmNADEAKAQQELVKQLSTLPRDNYNLLSYIcrFLHeIQ--LNCAVNKMSVDNLATVIGVNLIRSKVEDP-- 303
Cdd:cd04382  94 KEFMEAAE--ILDEDNSRAALYQAISELPQPNRDTLAFL--ILH-LQrvAQSPECKMDINNLARVFGPTIVGYSVPNPdp 168

                       170
                ....*....|....*..
gi 83582813 304 AVIMRGTPQIQRVMTMM 320
Cdd:cd04382 169 MTILQDTVRQPRVVERL 185

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 83582813 132 FGQRLDETVAYEqkfgpHLVPILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLK 211
Cdd:cd04377   1 FGVSLSSLTSED-----RSVPLVLEKLLEHIEMHGLYTEGIYRKSGSANKIKELRQGLDTDPDSVNLEDYPIHVITSVLK 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 212 LYLRDLPEPVVPWSQYEGFLlcgqlmNADEAKAQQELVKQLST----LPRDNYNLLSYICRFLHEIQLNCAVNKMSVDNL 287
Cdd:cd04377  76 QWLRELPEPLMTFELYENFL------RAMELEEKQERVRALYSvleqLPRANLNTLERLIFHLVRVALQEEVNRMSANAL 149

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 83582813 288 ATVIGVNLIRS-KVEDPAVIMRGTPQIQRVMTMMIRD 323
Cdd:cd04377 150 AIVFAPCILRCpDTADPLQSLQDVSKTTTCVETLIKE 186

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 83582813 149 HLVPILVEKCaEFILEHgVSEEGIFRLPGQDNLVKQLRDAFDAGErpsfDRDTDVHT--VASLLKLYLRDLPEPVVPWSQ 226
Cdd:cd04394  19 NVPKFLVDAC-TFLLDH-LSTEGLFRKSGSVVRQKELKAKLEGGE----ACLSSALPcdVAGLLKQFFRELPEPLLPYDL 92

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 83582813 227 YEGFLLCGQLMNADEAKAQQELVKQLstLPRDNYNLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRS 298
Cdd:cd04394  93 HEALLKAQELPTDEERKSATLLLTCL--LPDEHVNTLRYFFSFLYDVAQRCSENKMDSSNLAVIFAPNLFQS 162

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 83582813 150 LVPILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDAGERP--SFDRDTDVHTVASLLKLYLRDLPEPVVPWSQY 227
Cdd:cd04387  15 KVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDvsVMLSEMDVNAIAGTLKLYFRELPEPLFTDELY 94

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 83582813 228 EGFLlcGQLMNADEAKAQQELVKQLSTLPRDNYNLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIRSKVED 302
Cdd:cd04387  95 PNFA--EGIALSDPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVFGPTLLRPSEKE 167

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 151 VPILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDAGERPSFDRDTDVHTVASLLKLYLRDLPEPVVPWSQYEGF 230
Cdd:cd04407  15 VPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKLENYPIHAITGLLKQWLRELPEPLMTFAQYNDF 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 231 LLCGQLMNADEakAQQELVKQLSTLPRDNYNLLSYICRFLHEIQLNCAVNKMSVDNLATVIGVNLIR-SKVEDPAVIMRG 309
Cdd:cd04407  95 LRAVELPEKQE--QLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVFAPCLLRcPDSSDPLTSMKD 172

                       170
                ....*....|....
gi 83582813 310 TPQIQRVMTMMIRD 323
Cdd:cd04407 173 VAKTTTCVEMLIKE 186

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 83582813 132 FGQRLDETVAYEQKFGPHLVPILVEKCAEFILEHGVSEEGIFRLPGQDNLVKQLRDAFDAGERPSFDrDTDVHTVASLLK 211
Cdd:cd04381   1 FGASLSLAVERSRCHDGIDLPLVFRECIDYVEKHGMKCEGIYKVSGIKSKVDELKAAYNRRESPNLE-EYEPPTVASLLK 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 83582813 212 LYLRDLPEPVVP---WSQYEGflLCGQLmnaDEAKAQQELVKQLSTLPRDNYNLLSYICRFLHEIQLNCAVNKMSVDNLA 288
Cdd:cd04381  80 QYLRELPEPLLTkelMPRFEE--ACGRP---TEAEREQELQRLLKELPECNRLLLAWLIVHMDHVIAQELETKMNIQNIS 154

                ...
gi 83582813 289 TVI 291
Cdd:cd04381 155 IVL 157

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. 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 83582813  15 PNPLERPIKVGWLKKQR-SIVKNWQQRYFVLRAQQLYYYKDEEDSKPQGCMYLPGSTVKEIATNPEEAGKFVFEVipass 93
Cdd:cd13248   1 RDPNAPVVMSGWLHKQGgSGLKNWRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAPPSDEISRKFAFKA----- 75

                        90       100       110
                ....*....|....*....|....*....|.
gi 83582813  94 dqNRIGQDSYVLMASSQVEMEEWVKFLRRVA 124
Cdd:cd13248  76 --EHANMRTYYFAADTAEEMEQWMNAMSLAA 104