Type:Protein
SpeciesReactivity:H
B=Bovine;Ca=Cat;Ch=Chicken;D=Dog;EQ=Equine;GP=GuineaPig;H=Human;M=Mouse;P=Porcine;Pr=Primate;R=Rat;Rb=Rabbit;Y=Yeast;Xe=Xenopus;Ze=Zebrafish;;;;NA-NotApplicable;STP=Step-TactinProteins;AllApoER2,alsoknownasLRP8,isanLDLreceptorfamilyproteinthatisinvolvedinnervoussystemdevelopmentandfunction.1,2HumanApoER2hasa794aaextracellulardomain(ECD)anda116aacytoplasmicregion.TheECDcontainssevenLDLRclassArepeatsfollowedbytwoEGF-likerepeats,fiveLDLRclassBrepeats,andaregionrichinO-linkedglycosylation.AlternativelysplicedvariantsofhumanApoER2havedeletionsofLDLR-Arepeats#4-7,theO-linkedglycosylationregion,orapproximatelyhalfofthecytoplasmicdomain.3CleavageofApoER2byγ-secretase,metalloproteases,andfurin-likeenzymesresultsintheliberationofthecytoplasmic,extracellular,andligandbindingdomains.4-6ThecytoplasmicNPxYmotifbindstoPTBdomain-containingadaptorproteins.7-10Amongthese,FE65andPSD95coupleApoER2withAPPortheNMDAreceptor,respectively.9,10ApoER2andNMDAreceptorligandsmodulateadaptorinteractions,NMDA-mediatedioncurrents,andtheproteolyticprocessingofbothApoER2andAPP.9-12ApoER2andtheNMDAreceptoralsoassociateextracellularly.10ApoER2bindsApoE-containinglipoproteinsandthelargemodularprotein,reelin.13ReelinsignalingthroughApoER2iscriticalforneuronalmigrationandpositioninginthedevelopingbrain.13Intheadultbrain,ApoER2functionsinhippocampalsynapsematuration,synapticplasticity,andmemoryformation.7,11,14,15ApoER2isalsoexpressedattheneuromuscularjunctionbutdoesnotappeartoparticipateinthedevelopmentorfunctionofthatstructure.16DeficitsinApoER2,reelin,andApoEfunctionhavebeenlinkedtoseveralcognitiveandmooddisorders.1WithintheECD,humanApoER2shares89%aasequenceidentitywithmouseandratApoER2.Itshares46%and48%aasequenceidentitywithhumanLDLRandVLDLR,respectively.
