EntrezGeneSummary | Beta-cateninisanadherensjunctionprotein.Adherensjunctions(AJs;alsocalledthezonulaadherens)arecriticalfortheestablishmentandmaintenanceofepitheliallayers,suchasthoseliningorgansurfaces.AJsmediateadhesionbetweencells,communicateasignalthatneighboringcellsarepresent,andanchortheactincytoskeleton.Inservingtheseroles,AJsregulatenormalcellgrowthandbehavior.Atseveralstagesofembryogenesis,woundhealing,andtumorcellmetastasis,cellsformandleaveepithelia.Thisprocess,whichinvolvesthedisruptionandreestablishmentofepithelialcell-cellcontacts,mayberegulatedbythedisassemblyandassemblyofAJs.AJsmayalsofunctioninthetransmissionofthe"contactinhibition"signal,whichinstructscellstostopdividingonceanepithelialsheetiscomplete.[suppliedbyOMIM].
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UniProtSummary | FUNCTION:InvolvedintheregulationofcelladhesionandinsignaltransductionthroughtheWntpathway. SUBUNITSTRUCTURE:Twoseparatepoolsarefoundinthecytoplasm:oneisPSEN1/cadherin/catenincomplexwhichanchorstotheactincytoskeleton.TheotherpoolispartofalargecomplexcontainingAXIN1,AXIN2,APC,CSNK1A1andGSK3BthatpromotesphosphorylationonN-terminalSerandThrresiduesandubiquitinationofCTNNB1viaBTRCanditssubsequentdegradationbytheproteasome.Wnt-dependentactivationofDVLantagonizestheactionofGSK3B.WhenGSK3Bactivityisinhibitedthecomplexdissociates,CTNNB1isdephosphorylatedandisnolongertargetedfordestruction.Thestabilizedproteintranslocatestothenucleus,whereitbindsTCF/LEF-1familymembers,TBP,BCL9andpossIBLyalsoRUVBL1andCHD8.BindsCTNNBIPandEP300.CTNNB1formsaternarycomplexwithLEF1andEP300thatisdisruptedbyCTNNBIP1bindingBysimilarity.InteractswithTAX1BP3(viathePDZdomain);thisinteractioninhibitsthetranscriptionalactivityofCTNNB1Bysimilarity.InteractswithAJAP1,BAIAP1,CARM1,CTNNA3,CXADRandPCDH11Y.BindsSLC9A3R1.InteractswithGLIS2andMUC1.InteractswithSLC30A9.InteractswithXIRP1Bysimilarity.InteractswithPTPRU(viathecytoplasmicjuxtamembranedomain). SUBCELLULARLOCATION:Cytoplasm.Nucleus.Cytoplasm?cytoskeleton.Note=Cytoplasmicwhenitisunstabilized(highlevelofphosphorylation)orboundtoCDH1.Translocatestothenucleuswhenitisstabilized(lowlevelofphosphorylation).InteractionwithGLIS2andMUC1promotesnucleartranslocation. TISSUESPECIFICITY:Expressedinseveralhairfolliclecelltypes:basalandperipheralmatrixcells,andcellsoftheouterandinnerrootsheats.Expressedincolon. PTM:PhosphorylationbyGSK3BrequirespriorphosphorylationofSer-45byanotherkinase.PhosphorylationproceedsthenfromThr-41toSer-37andSer-33. EGFstimulatestyrosinephosphorylation.PhosphorylationonTyr-654decreasesCDH1bindingandenhancesTBPbinding. UbiquitinatedbyaE3ubiquitinligasecomplexcontainingUBE2D1,SIAH1,CACYBP/SIP,SKP1A,APCandTBL1XProbable.Itsubiquitinationleadstoitssubsequentproteasomaldegradation. DISEASE:ActivatingmutationsinCTNNB1haveoncogenicactivityresultingintumordevelopment.Somaticmutationsarefoundinvarioustumortypes,includingcoloncancers,ovarianandprostatecarcinomas,hepatoblastoma(HB),hepatocellularcarcinoma(HCC).HBsaremalignantembryonaltumorsmainlyaffectingyoungchildreninthefirstthreeyearsoflife. DefectsinCTNNB1areacauseofpilomatrixoma(PTR)[MIM:132600];acommonbenignskintumor. DefectsinCTNNB1areacauseofmedulloblastoma(MDB)[MIM:155255].MDBisamalignant,invasiveembryonaltumorofthecerebellumwithapreferentialmanifestationinchildren. AchromosomalrearrangementinvolvingCTNNB1maybeacauseofsalivaryglandpleiomorphicadenomas(PA)[181030].Pleiomorphicadenomasarethemostcommonbenignepithelialtumorsofthesalivarygland.Translocationt(3;8)(p21;q12)withPLAG1. SIMILARITY:Belongstothebeta-cateninfamily. Contains12ARMrepeats.
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