OMIMOnlineMendelianInheritanceinManAll DatabasesPubMedNucleotideProteinGenomeStructurePMCTaxonomyOMIM SearchPubMedProteinNucleotideCoreNucleotideGSSESTStructureGenomeBooksCancerChromosomesConservedDomainsdbGaP3DDomainsGeneGenomeProjectGENSATGEOProfilesGEODataSetsHomoloGeneJournalsMeSHNCBIWebSiteNLMCatalogOMIAOMIMPMCPopSetProbeProteinClustersPubChemBioAssayPubChemCompoundPubChemSubstanceSNPTaxonomyToolKitUniGeneUniSTSLimitsPreview/IndexHistoryClipboardDetailsDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardAll1OMIMdbSNP0OMIMUniSTS0*610586LinksRHOGTPaseACTIVATINGPROTEIN24ARHGAP24AlternativetitlessymbolsRAC1ANDCDC42SPECIFICGTPaseACTIVATINGPROTEIN72KDRCGAP72p73RHOGAPFILAMINAASSOCIATEDRHOGAPFILGAPGenemaplocus4q21TEXTDESCRIPTIONARHGAPssuchasARHGAP24encodenegativeregulatorsofRhoGTPases(seeARHA165390)whichareimplicatedinactinremodelingcellpolarityandcellmigration(KatohandKatoh2004)CLONINGBysearchinganESTdatabaseforsequencessimilartoARHGAP22(610585)KatohandKatoh(2004)identifiedARHGAP24Thededuced748aminoacidproteinhasanNterminalpleckstrinhomology(PH)domainfollowedbyaRhoGAPdomainandaCterminalcoiledcoildomainUsingaPCRbasedsubtractionhybridizationapproachtoidentifygenesupregulatedduringcapillarytubeformationinhumanumbilicalveinendothelialcells(HUVECs)followedbydatabaseanalysisandPCRofanendothelialcellcDNAlibrarySuetal(2004)clonedARHGAP24whichtheycalledp73Thepredictedp73proteincontains655aminoacidsandhasacalculatedmolecularmassof73kDNorthernblotanalysisdetecteda45kbtranscriptinHUVECsandvirtualNorthernblotanalysisofvariouscelllinesshowedhighp73expressionrestrictedtoHUVECsandvascularsmoothmusclecellsUsingquantitativeRTPCRSuetal(2004)foundthattheratioofp73expressioninHUVECsoverthemedianexpressionin5otherprimarytissuescorrelatedwiththeratioobtainedwiththeendothelialmarkerCD31(PECAM1173445)suggestingthatp73isexpressedspecificallyinendothelialcellsBydatabaseanalysisLavelinandGeiger(2005)identifiedARHGAP24whichtheycalledRCGAP72Thededuced655aminoacidproteinhasacalculatedmolecularmassof72kDandshares87%aminoacididentityitsmousehomologNorthernblotanalysisdetectedvariableexpressionofRcgap72inallmousetissuesexaminedwithhighestexpressioninkidneyNorthernandWesternblotanalysesofseveralhumancelllinesdetectedRCGAP72expressioninHeLacellsandanonsmallcelllungcarcinomacelllineonlyWesternblotanalysisofHeLacellsrevealedan80kDRCGAP72proteinImmunofluorescencemicroscopyoftransfectedmousefibroblastsshowedfluorescencetaggedRCGAP72associatedwithactinstressfibersIncaninekidneycellsitcolocalizedprimarilyalongalphaactinin(seeACTN1102575)containingadherensjunctionsandinthenucleusUsingtheCterminusofFLNA(300017)inayeast2hybridscreenofaspleencDNAlibraryOhtaetal(2006)clonedARHGAP24whichtheycalledFILGAPThededuced748aminoacidproteinhasacalculatedmolecularmassof84kDOhtaetal(2006)determinedthatthep73(Suetal2004)/RCGAP72(LavelinandGeiger2005)proteinisencodedbyasplicevariantandlacksthePHdomainofthefulllengthFILGAPproteinNorthernblotanalysisdetectedtranscriptsof30and40kbinmosttissuesexaminedwithhighestexpressioninkidneyandFILGAPwaswidelyexpressedinhumancelllinesGENEFUNCTIONSuetal(2004)foundthatp73clonedfromHUVECsshowedGTPaseactivitytoRHObutnottoRAC(RAC1602048)orCDC42(116952)p73wasupregulatedinendothelialcellsgrowingina3dimensional(3D)matrixbutnotincellsgrowingona2DsurfaceKnockdownofp73inendothelialcellsbyantisensep73orsmallinterferingRNAreducedcellmigrationproliferationandcapillarytubeformationin3DgelsAp73mutantlackingGAPactivitycausedsimilarresultsandantisensep73inhibitedbloodvesselmigrationinamousemodelofangiogenesisSuetal(2004)concludedthatp73isavascularcellspecificGAPimportantinmodulationofangiogenesisLavelinandGeiger(2005)foundthatthelevelsofactiveRAC1andCDC42weresignificantlyreducedinHeLacellsoverexpressingRCGAP72whereasthelevelofRHOAGTPwasnotaffectedOverexpressionofRCGAP72inratfibroblastsinducedcellroundingwithpartialorcompletedisruptionofactinstressfibersandformationofmembraneruffleslamellipodiaandfilopodiaMutationanalysisindicatedthatcytoskeletallocalizationofRCGAP72anditsinteractionwithRAC1and/orCDC42wereessentialfordisruptionofstressfibersIncontrastinductionoffilopodiadependedontheGAPactivityofRCGAP72irrespectiveofcytoskeletallocalizationBymutationanalysisOhtaetal(2006)determinedthatthecoiledcoildomainofFILGAPinteractedwiththeCterminalrepeatsofFLNAFLNAbindingtargetedFILGAPtositesofmembraneprotrusioninmammaliancelllineswhereFILGAPmediatedROCK(seeROCK1601702)dependentdownregulationofRACactivityandsuppressedleadinglamellarformationOverexpressionofFILGAPinducednumerousblebsaroundthecellperipheryandphosphorylationofFILGAPbyROCKwasrequiredforFILGAPmediatedblebformationGENESTRUCTUREKatohandKatoh(2004)determinedthattheARHGAP24genecontainsatleast10exonsMAPPINGBygenomicsequenceanalysisKatohandKatoh(2004)mappedtheARHGAP24genetochromosome4q21TheregioncontainingARHGAP24andthatcontainingARHGAP22onchromosome10q11appeartobeparalogousREFERENCES1KatohMKatohMIdentificationandcharacterizationofARHGAP24andARHGAP25genesinsilicoIntJMolecMed143333382004PubMedID152547882LavelinIGeigerBCharacterizationofanovelGTPaseactivatingproteinassociatedwithfocaladhesionsandtheactincytoskeletonJBiolChem280717871852005PubMedID156111383OhtaYHartwigJHStosselTPFilGAPaRhoandROCKregulatedGAPforRacbindsfilaminAtocontrolactinremodellingNatureCellBiol88038142006PubMedID168621484SuZJHahnCNGoodallGJReckNMLeskeAFDavyAKremmidiotisGVadasMAGambleJRAvascularcellrestrictedRhoGAPp73RhoGAPisakeyregulatorofangiogenesisProcNatAcadSci10112212122172004PubMedID15302923CREATIONDATEPatriciaAHartz11/21/2006EDITHISTORYmgross11/21/2006mgross11/21/2006Copyright©19662007JohnsHopkinsUniversityDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardDisclaimerWritetotheHelpDeskPrivacyPolicyNCBINLMNIH