UniProtSummary | FUNCTION:Cadherinsarecalcium-dependentcelladhesionproteins.Theypreferentiallyinteractwiththemselvesinahomophilicmannerinconnectingcells;cadherinsmaythuscontributetothesortingofheterogeneouscelltypes.CDH1isinvolvedinmechanismsregulatingcell-celladhesions,mobilityandproliferationofepithelialcells.Hasapotentinvasivesuppressorrole.Itisaligandforintegrinalpha-E/beta-7. E-Cad/CTF2promotesnon-amyloidogenicdegradationofAbetaprecursors.HasastronginhibitoryeffectonAPPC99andC83production. SUBUNITSTRUCTURE:Homodimer;disulfide-linked.Interactsdirectly,viathecytoplasmicdomain,withCTNNB1orJUPtoformthePSEN1/cadherin/cateninadhesioncomplexwhichconnectstotheactinskeletonthroughtheactinbindingofalpha-catenin.InteractionwithPSEN1,cleavesCDH1resultinginthedisassociationofcadherin-basedadherensjunctions(CAJs).InteractswithAJAP1,CTNND1andDLGAP5. SUBCELLULARLOCATION:Celljunction.Cellmembrane;Single-passtypeImembraneprotein.Note:ColocalizeswithDLGAP5atsitesofcell-cellcontactinintestinalepithelialcells.AnchoredtoactinMICROFILamentsthroughassociationwithalpha-,beta-andgamma-catenin.Sequentialproteolysisinducedbyapoptosisorcalciuminflux,resultsintranslocationfromsitesofcell-cellcontacttothecytoplasm. TISSUESPECIFICTIY:Non-neuralepithelialtissues. PTM:Duringapoptosisorwithcalciuminflux,cleavedbyamembrane-boundmetalloproteinase(ADAM10),PS1/gamma-secretaseandcaspase-3toproducefragmentsofabout38kDa(E-CAD/CTF1),33kDa(E-CAD/CTF2)and29kDa(E-CAD/CTF3),respectively.Processingbythemetalloproteinase,inducedbycalciuminflux,causesdisruptionofcell-celladhesionandthesubsequentreleaseofbeta-cateninintothecytoplasm.Theresidualmembrane-tetheredcleavageproductisrapidlydegradedviaanintracellularproteolyticpathway.Cleavagebycaspase-3releasesthecytoplasmictailresultingindisintegrationoftheactinmicrofilamentsystem.Thegamma-secretase-mediatedcleavagepromotesdisaaaemblyofadherensjunctions. INVOLVEMENTINDISEASE:DefectsinCDH1areinvolvedindysfunctionofthecell-celladhesionsystem,triggeringcancerinvasion(gastric,breast,ovary,endometriumandthyroid)andmetastasis. DefectsinCDH1areacauseofgastriccancer[MIM:137215];alsoknownashereditaryfamilialdiffusegastriccancer(HDGC). DefectsinCDH1areacauseofsusceptibilitytoendometrialcancer[MIM:608089]. DefectsinCDH1areassociatedwithovariancancer[MIM:167000].OvariancanceristheleADIngcauseofdeathfromgynecologicmalignancy.Itischaracterizedbyadvancedpresentationwithloco-regionaldisseminationintheperitonealcavityandtherareincidenceofvisceralmetastases.Thesetypicalfeaturesrelatetothebiologyofthedisease,whichisaprincipaldeterminantofoutcome. SEQUENCESIMILARITIES:Contains5cadherindomains. SEQUENCECAUTION:ThesequenceAAA61259.1differsfromthatshown.Reason:Frameshiftatpositions16,22,25,28,31,34,52,67,73,76,94,102,633and636. |