OMIMOnlineMendelianInheritanceinManAll DatabasesPubMedNucleotideProteinGenomeStructurePMCTaxonomyOMIM SearchPubMedProteinNucleotideCoreNucleotideGSSESTStructureGenomeBooksCancerChromosomesConservedDomainsdbGaP3DDomainsGeneGenomeProjectGENSATGEOProfilesGEODataSetsHomoloGeneJournalsMeSHNCBIWebSiteNLMCatalogOMIAOMIMPMCPopSetProbeProteinClustersPubChemBioAssayPubChemCompoundPubChemSubstanceSNPTaxonomyToolKitUniGeneUniSTSLimitsPreview/IndexHistoryClipboardDetailsDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardAll1OMIMdbSNP0OMIMUniSTS0*609870LinksRHOGTPaseACTIVATINGPROTEIN21ARHGAP21AlternativetitlessymbolsGTPaseACTIVATINGPROTEINRHO21KIAA1424RHOGTPaseACTIVATINGPROTEIN10FORMERLYARHGAP10FORMERLYGenemaplocus10p123TEXTDESCRIPTIONARHGAP21functionspreferentiallyasaGTPaseactivatingprotein(GAP)forCDC42(116952)andregulatestheARP2/3complex(604221)andFactindynamicsattheGolgithroughcontrolofCDC42activity(Duboisetal2005)CLONINGByscreeninganadultbraincDNAlibraryforcDNAslikelytoencodelargeproteinsNagaseetal(2000)isolatedapartialcDNAencodingARHGAP21whichtheycalledKIAA1424RTPCRELISAdetectedwideexpressionofKIAA1424withhighestexpressioninbrainandspinalcordWithinbrainhighestexpressionwasincorpuscallosumandhippocampusfollowedbyamygdalacerebellumcaudatenucleusandsubstantianigraBysearchingdatabasesforpotentialcytoskeletalproteinsfollowedbyPCRofabraincDNAlibraryandRACEBasseresetal(2002)obtainedafulllengthcDNAencodingARHGAP21whichtheytermedARHGAP10Thepredicted1957aminoacidproteincontainsapleckstrinhomology(PH)domainaRHOGAPdomainandaPDZdomainwithaglycinerichnucleotidebindingPloopNorthernblotanalysisrevealedwideexpressionofa75kbtranscriptwithhighestexpressioninbrainheartskeletalmuscleandplacentaExpressionwasvariableinseveralcancercelllinesUsingimmunoblotandimmunofluorescenceanalysesDuboisetal(2005)foundthatARHGAP21wasexpressedasajuxtanuclearGolgicomplexproteinofmorethan250kDItsassociationwiththeGolgicomplexwasreminiscentofARF1(103180)distributionGENEFUNCTIONUsingrealtimeRTPCRanalysisBasseresetal(2002)showedthathemopoieticstemcellsstimulatedtowardsmyeloidorerythroiddifferentiationhadamarkedincreaseinARHGAP21expressionTheyconcludedthatARHGAP21isacytoskeletalRHOGAPproteininvolvedincelldifferentiationUsingyeast2hybridanalysisDuboisetal(2005)isolatedARHGAP21viaitsinteractionwithactivatedmutantsofARF6(600464)andARF1GSTpulldownandmutationanalysesshowedthattheinteractionsoccurredthroughthePHdomainofARHGAP21RHOGAPassaysindicatedthatARHGAP21actedpreferentiallyonCDC42overRHOA(ARHA165390)andRAC1(602048)Smallinterfering(siRNA)treatmentofARHGAP21ledtoconstitutiveactivationofCDC42thatresultedinactincytoskeletonremodelingsuggestingthatARHGAP21isrequiredforGolgicomplexorganizationLossofARHGAP21alsocausedamassiveactivation/recruitmentoftheARP2/3complexinthejuxtanuclearregionDuboisetal(2005)concludedthatARHGAP21isadownstreampartnerofARF1thatregulatesGolgistructureandfunctionthroughcontrolofCDC42activityAlphacatenin(CTNNA1116805)isrecruitedbybetacatenin(CTNNB1116806)afterinteractionofCTNNB1withthecytoplasmicdomainofEcadherin(CDH1192090)areceptorfortheListeriamonocytogenesInlAproteinByyeast2hybridanalysisSousaetal(2005)identifiedARHGAP21asaCTNNA1interactingpartnerARHGAP21andCTNNA1colocalizedatcellcelljunctionsandARHGAP21wasrecruitedtoLmonocytogenesentrysitesKnockdownofARHGAP21impairedbothLmonocytogenesentryandCTNNA1recruitmentatcellcellcontactsIncontrastoverexpressionofARHGAP21enhancedCTNNA1levelsatcellcelljunctionsandinhibitedentryofthebacteriumGENESTRUCTUREBasseresetal(2002)determinedthattheARHGAP21genecontains25exonsandspansatleast88kbMAPPINGBygenomicsequenceanalysisBasseresetal(2002)mappedtheARHGAP21genetochromosome10p1232Theyidentifiedanintronlesscopyonchromosome6thatmayrepresentaretropseudogeneREFERENCES1BasseresDSTizzeiEVDuarteAASCostaFFSaadSTOARHGAP10anovelhumangenecodingforapotentiallycytoskeletalRhoGTPaseactivatingproteinBiochemBiophysResCommun2945795852002PubMedID120568062DuboisTPaleottiOMironovAAJrFraisierVStradalTEBDeMatteisMAFrancoMChavrierPGolgilocalizedGAPforCdc42functionsdownstreamofARF1tocontrolArp2/3complexandFactindynamicsNatureCellBiol73533642005PubMedID157935643NagaseTKikunoRIshikawaKHirosawaMOharaOPredictionofthecodingsequencesofunidentifiedhumangenesXVIThecompletesequencesof150newcDNAclonesfrombrainwhichcodeforlargeproteinsinvitroDNARes765732000PubMedID107181984SousaSCabanesDArchambaudCCollandFLemichezEPopoffMBoissonDupuisSGouinELecuitMLegrainPCossartPARHGAP10isnecessaryforalphacateninrecruitmentatadherensjunctionsandforListeriainvasionNatureCellBiol79549602005PubMedID16184169CREATIONDATEPaulJConverse1/31/2006EDITHISTORYcarol1/2/2007carol10/16/2006carol10/16/2006mgross1/31/2006Copyright©19662007JohnsHopkinsUniversityDisplayTitlesDetailedClinicalSynopsisAllelicVariantsASN1XMLLinkOutRelatedEntriesBookLinksGeneLinksGenomeLinksGEOProfileLinksHomoloGeneLinksNucleotideLinksOMIALinksPubChemBioAssayLinksPMCLinksProteinLinksPubMed(calculated)LinksPubMed(cited)LinksSNPLinksGeneGenotypeLinksStructureLinksUniGeneLinksUniSTSLinksShow5102050100200500SendtoTextFilePrinterClipboardDisclaimerWritetotheHelpDeskPrivacyPolicyNCBINLMNIH