EntrezGeneSummary | Thisgeneisaclassicalcadherinfromthecadherinsuperfamily.Theencodedproteinisacalciumdependentcell-celladhesionglycoproteincomprisedoffiveextracellularcadherinrepeats,atransmembraneregionandahighlyconservedcytoplasmictail.Mutationsinthisgenearecorrelatedwithgastric,breast,colorectal,thyroidandovariancancer.Lossoffunctionisthoughttocontributetoprogressionincancerbyincreasingproliferation,invasion,and/ormetastasis.Theectodomainofthisproteinmediatesbacterialadhesiontomammaliancellsandthecytoplasmicdomainisrequiredforinternalization.Identifiedtranscriptvariantsarisefrommutationatconsensussplicesites. |
UniProtSummary | FUNCTION:SwissProt:P12830#E-Cad/CTF2promotesnon-amyloidogenicdegradationofAbetaprecursors.HasastronginhibitoryeffectonAPPC99andC83production. SIZE:882aminoacids;97456Da SUBUNIT:Homodimer;disulfide-linked.Interactsdirectly,viathecytoplasmicdomain,withCTNNB1orJUPtoformthePSEN1/cadherin/cateninadhesioncomplexwhichconnectstotheactinskeletonthroughtheactinbindingofalpha-catenin.InteractionwithPSEN1,cleavesCDH1resultinginthedisassociationofcadherin-basedadherensjunctions(CAJs).InteractswithAJAP1,CTNND1andDLG7. SUBCELLULARLOCATION:Celljunction.Cellmembrane;Single-passtypeImembraneprotein.Note=ColocalizeswithDLG7atsitesofcell-cellcontactinintestinalepithelialcells.AnchoredtoactinMICROFILamentsthroughassociationwithalpha-,beta-andgamma-catenin.Sequentialproteolysisinducedbyapoptosisorcalciuminflux,resultsintranslocationfromsitesofcell-cellcontacttothecytoplasm. TISSUESPECIFICITY: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. DISEASE:"SwissProt:P12830#DefectsinCDH1areinvolvedindysfunctionofthecell-celladhesionsystem,triggeringcancerinvasion(gastric,breast,ovary,endometriumandthyroid)andmetastasis.&DefectsinCDH1areacauseofhereditarydiffusegastriccancer(HDGC)[MIM:137215].&DefectsinCDH1areacauseofsusceptibilitytoendometrialcancer[MIM:608089]." SIMILARITY:SwissProt:P12830##Contains5cadherindomains. |