UniProtSummary | FUNCTION:Keyregulatorofentryintocelldivisionthatactsasatumorsuppressor.ActsasatranscriptionrepressorofE2F1targetgenes.Theunderphosphorylated,activeformofRB1interactswithE2F1andrepressesitstranscriptionactivity,leADIngtocellcyclearrest.Directlyinvolvedinheterochromatinformationbymaintainingoverallchromatinstructureand,inparticular,thatofconstitutiveheterochromatinbystabilizinghistonemethylation.RecruitsandtargetshistonemethyltransferasesSUV39H1,SUV420H1andSUV420H2,leadingtoepigenetictranscriptionalrepression.ControlshistoneH4"Lys-20"trimethylation.InhibitstheintrinsickinaseactivityofTAF1.MediatestranscriptionalrepressionbySMARCA4/BRG1byrecruitingahistonedeacetylase(HDAC)complextothec-FOSpromoter.Inrestingneurons,transcriptionofthec-FOSpromoterisinhibitedbyBRG1-dependentrecruitmentofaphospho-RB1-HDAC1repressorcomplex.Uponcalciuminflux,RB1isdephosphorylatedbycalcineurin,whichleadstoreleaseoftherepressorcomplexBysimilarity.Incaseofviralinfections,interactionswithSV40largeTantigen,HPVE7proteinoradenovirusE1AproteininducethedisassemblyofRB1-E2F1complextherebydisruptingRB1"sactivity. SUBUNITSTRUCTURE:InteractswithATAD5.InteractswithPRMT2Bysimilarity.ThehypophosphorylatedforminteractswithandsequesterstheE2F1transcriptionfactor.InteractswithheterodimericE2F/DPtranscriptionfactorcomplexescontainingTFDP1andeitherE2F1,E2F3,E2F4orE2F5,orTFDP2andE2F4.TheunphosphorylatedforminteractswithEID1,ARID3B,KDM5A,SUV39H1,MJD2A/JHDM3AandTHOC1.InteractswiththeN-terminaldomainofTAF1.InteractswithAATF,DNMT1,LIN9,LMNA,SUV420H1,SUV420H2,PELP1andTMPO-alpha.MayinteractwithNDC80.InteractswithGRIP1andUBR4.InteractswithARID4AandKDM5B.InteractswithE4F1andLIMD1.InteractswithSMARCA4/BRG1ANDHDAC1Bysimilarity.InteractswithadenovirusE1Aprotein,HPVE7proteinandSV40largeTantigen.InteractswithPSMA3andUSP4.Interacts(whenmethylatedatLys-860)withL3MBTL1. SUBCELLULARLOCATION:Nucleus. TISSUESPECIFICITY:Expressedintheretina. DOMAIN:ThePocketdomainbindstothethreonine-phosphorylateddomainC,therebypreventinginteractionwithheterodimericE2F/DPtranscriptionfactorcomplexes. PTM:PhosphorylatedinG1,therebyreleasingE2F1whichisthenabletoactivatecellgrowth.DephosphorylatedatthelateMphase.SV40largeTantigen,HPVE7andadenovirusE1Abindtotheunderphosphorylated,activeformofpRb.PhosphorylationatThr-821andThr-826promotesinteractionbetweentheC-terminaldomainCandthePocketdomain,andtherebyinhibitsinteractionswithheterodimericE2F/DPtranscriptionfactorcomplexes.DephosphorylatedatSer-795bycalcineruinuponcalciumstimulation. N-terminusismethylatedbyMETTL11A/NTM1Bysimilarity.MonomethylatedatLys-860bySMYD2,promotinginteractionwithL3MBTL1. INVOLVEMENTINDISEASE:DefectsinRB1arethecauseofchildhoodcancerretinoblastoma(RB)[MIM:180200].RBisacongenitalmalignanttumorthatarisesfromthenuclearlayersoftheretina.Itoccursinabout1:20"000livebirthsandrepresentsabout2%ofchildhoodmalignancies.Itisbilateralinabout30%ofcases.AlthoughmostRBappearsporadically,about20%aretransmittedasanautosomaldominanttraitwithincompletepenetrance.Thediagnosisisusuallymadebeforetheageof2yearswhenstrabismusoragraytoyellowreflexfrompupil("cateye")isinvestigated. DefectsinRB1areacauseofsusceptibilitytobladdercancer(BLC)[MIM:109800].Amalignancyoriginatingintissuesoftheurinarybladder.Itoftenpresentswithmultipletumorsappearingatdifferenttimesandatdifferentsitesinthebladder.Mostbladdercancersaretransitionalcellcarcinomas.Theybeginincellsthatnormallymakeuptheinnerliningofthebladder.Othertypesofbladdercancerincludesquamouscellcarcinoma(cancerthatbeginsinthin,flatcells)andadenocarcinoma(cancerthatbeginsincellsthatmakeandreleasemucusandotherfluids).Bladdercancerisacomplexdisorderwithbothgeneticandenvironmentalinfluences. DefectsinRB1areacauseofosteogenicsarcoma(OSRC)[MIM:259500]. SEQUENCESIMILARITIES:Belongstotheretinoblastomaprotein(RB)family. |