EntrezGeneSummary | Thisgeneisatargetgeneofthetranscriptionfactortumorproteinp53.Theencodedproteinisanuclearphosphoproteinthatbindsandinhibitstransactivationbytumorproteinp53,aspartofanautoregulatorynegativefeedbackloop.Overexpressionofthisgenecanresultinexcessiveinactivationoftumorproteinp53,diminishingitstumorsuppressorfunction.ThisproteinhasE3ubiquitinligaseactivity,whichtargetstumorproteinp53forproteasomaldegradation.Thisproteinalsoaffectsthecellcycle,apoptosis,andtumOrigenesisthroughinteractionswithotherproteins,includingretinoblastoma1andribosomalproteinL5.Morethan40differentalternativelysplicedtranscriptvariantshavebeenisolatedfrombothtumorandnormaltissues. |
UniProtSummary | FUNCTION:SwissProt:Q00987#InhibitsTP53/p53-andTP73/p73-mediatedcellcyclearrestandapoptosisbybindingitstranscriptionalactivationdomain.FunctionsasaubiquitinligaseE3,inthepresenceofE1andE2,towardp53anditself.Permitsthenuclearexportofp53andtargetsitforproteasome-mediatedproteolysis. SIZE:491aminoacids;55233Da SUBUNIT:Bindsp53,p73,ARF(P14),ribosomalproteinL5andspecificallytoRNA.Caninteractalsowithretinoblastomaprotein(RB),E1A-associatedproteinEP300andtheE2F1transcriptionfactor.Formsaternarycomplexwithp53andWWOX.InteractswithUSP7andTBRG1.IsoformMdm2-FdoesnotinteractwithTP53/p53.Interactswith,andubiquitinatesHIV-1Tat. SUBCELLULARLOCATION:Nucleus,nucleoplasm.Cytoplasm.Nucleus,nucleolus.Note=Expressedpredominantlyinthenucleoplasm.InteractionwithARF(P14)resultsinthelocalizationofbothproteinstothenucleolus.ThenucleolarlocalizationsignalsinbothARF(P14)andMDM2maybenecessarytoallowefficientnucleolarlocalizationofbothproteins. TISSUESPECIFICITY:Ubiquitous.IsoformMdm2-A,isoformMdm2-B,isoformMdm2-C,isoformMdm2-D,isoformMdm2-E,isoformMdm2-FandisoformMdm2-Gareobservedinarangeofcancersbutabsentinnormaltissues. DOMAIN:SwissProt:Q00987RegionIissufficientforbindingp53andinhibitingitsG1arrestandapoptosisfunctions.Italsobindsp73andE2F1.RegionIIcontainsmostofacentralacidicregionrequiredforinteractionwithribosomalproteinL5andaputativeC4-typezincfinger.TheRINGfingerdomainwhichcoordinatestwomoleculesofzincinteractsspecificallywithRNAwhetherornotzincispresentandmediatesthehetero-oligomerizationwithMDM4.ItisalsoessentialforitsubiquitinligaseE3activitytowardp53anditself. PTM:PhosphorylatedinresponsetoionizingrADIationinanATM-dependentmanner. DISEASE:SwissProt:Q00987#Seemstobeamplifiedincertaintumors(includingsofttissuesarcomas,osteosarcomasandgliomas).Ahigherfrequencyofsplicevariantslackingp53bindingdomainsequenceswasfoundinlate-stageandhigh-gradeovarianandbladdercarcinomas.Fourofthesplicevariantsshowlossofp53binding. SIMILARITY:BelongstotheMDM2/MDM4family.&Contains1RanBP2-typezincfinger.&Contains1RING-typezincfinger.&Contains1SWIBdomain. MISCELLANEOUS:MDM2RINGfingermutationsthatfailedtoubiquitinatep53invitrodidnottargetp53fordegradationwhenexpressedincells. |