载脂蛋白E抗体

载脂蛋白E抗体

ApolipoproteinE,amainapoproteinofthechylomicron,bindstoaspecificreceptoronlivercellsandperipheralcellsandisessentialforthenormalcatabolismoftriglyceride-richlipoproteinconstituents.ApoEexistsinthreemajorisoforms;E2,E3,andE4,whichdifferfromoneanotherbyasingleamino-acidsubstitution.ComparedwithE3andE4,E2exhibitsthelowestreceptorbindingaffinity.DefectsinApoEareacauseofhyperlipoproteinemiatypeIIIduetoincreasedplasmacholesterolandtriglycerideslevelswhicharetheconsequenceofimpairedclearanceofchylomicronandVLDLremnants.
Summary:Chylomicronremnantsandverylowdensitylipoprotein(VLDL)remnantsarerapidlyremovedfromthecirculationbyreceptor-mediatedendocytosisintheliver.ApolipoproteinE,amainapoproteinofthechylomicron,bindstoaspecificreceptoronlivercellsandperipheralcells.ApoEisessentialforthenormalcatabolismoftriglyceride-richlipoproteinconstituents.TheAPOEgeneismappedtochromosome19inaclusterwithAPOC1andAPOC2.DefectsinapolipoproteinEresultinfamilialdysbetalipoproteinemia,ortypeIIIhyperlipoproteinemia(HLPIII),inwhichincreasedplasmacholesterolandtriglyceridesaretheconsequenceofimpairedclearanceofchylomicronandVLDLremnants.[providedbyRefSeq,Jul2008].
Function:Mediatesthebinding,internalization,andcatabolismoflipoproteinparticles.ItcanserveasaligandfortheLDL(apoB/E)receptorandforthespecificapo-Ereceptor(chylomicronremnant)ofhepatictissues.
SubcellularLocation:Secreted.
TissueSpecificity:Occursinalllipoproteinfractionsinplasma.Itconstitutes10-20%ofverylowdensitylipoproteins(VLDL)and1-2%ofhighdensitylipoproteins(HDL).APOEisproducedinmostorgans.Significantquantitiesareproducedinliver,brain,spleen,lung,adrenal,ovary,kidneyandmuscle.
Post-translationalmodifications:SynthesizedwiththesialicacidattachedbyO-glycosidiclinkageandissubsequentlydesialylatedinplasma.O-glycosylatedwithcore1orpossiblycore8glycans.Thr-307isaminorglycosylationsitecomparedtoSer-308.
GlycatedinplasmaVLDLofnormalsubjects,andofhyperglycemicdiabeticpatientsatahigherlevel(2-3fold).
Phosphorylationsitesarepresentintheextracellularmedium.
DISEASE:DefectsinAPOEareacauseofhyperlipoproteinemiatype3(HLPP3)[MIM:107741];alsoknownasfamilialdysbetalipoproteinemia.IndividualswithHLPP3areclinicallycharacterizedbyxanthomas,yellowishlipiddepositsinthepalmarcrease,orlessspecificontendonsandonelbows.Thedisorderrarelymanifestsbeforethethirddecadeinmen.Inwomen,itisusuallyexpressedonlyafterthemenopause.ThevastmajorityofthepatientsarehomozygousforAPOE*2alleles.MoreseverecasesofHLPP3havealsobeenobservedinindividualsheterozygousforrareAPOEvariants.TheinfluenceofAPOEonlipidlevelsisoftensuggestedtohavemajorimplicationsfortheriskofcoronaryarterydisease(CAD).IndividualscarryingthecommonAPOE*4variantareathigherriskofCAD.
GeneticvariationsinAPOEareassociatedwithAlzheimerdiseasetype2(AD2)[MIM:104310].Itisalate-onsetneurodegenerativedisordercharacterizedbyprogressivedementia,lossofcognitiveabilities,anddepositionoffibrillaramyloidproteinsasintraneuronalneurofibrillarytangles,extracellularamyloidplaquesandvascularamyloiddeposits.Themajorconstituentoftheseplaquesistheneurotoxicamyloid-beta-APP40-42peptide(s),derivedproteolyticallyfromthetransmembraneprecursorproteinAPPbysequentialsecretaseprocessing.ThecytotoxicC-terminalfragments(CTFs)andthecaspase-cleavedproductssuchasC31derivedfromAPP,arealsoimplicatedinneuronaldeath.Note=TheAPOE*4alleleisgeneticallyassociatedwiththecommonlateonsetfamilialandsporadicformsofAlzheimerdisease.RiskforADincreasedfrom20%to90%andmeanageatonsetdecreasedfrom84to68yearswithincreasingnumberofAPOE*4allelesin42familieswithlateonsetAD.ThusAPOE*4genedoseisamajorriskfactorforlateonsetADand,inthesefamilies,homozygosityforAPOE*4wasvirtuallysufficienttocauseADbyage80.ThemechanismbywhichAPOE*4participatesinpathogenesisisnotknown.
DefectsinAPOEareacauseofsea-bluehistiocytedisease(SBHD)[MIM:269600];alsoknownassea-bluehistiocytosis.Thisdisorderischaracterizedbysplenomegaly,mildthrombocytopeniaand,inthebonemarrow,numeroushistiocytescontainingcytoplasmicgranuleswhichstainbrightbluewiththeusualhematologicstains.ThesyndromeistheconsequenceofaninheritedmetabolicdefectanalogoustoGaucherdiseaseandothersphingolipidoses.
DefectsinAPOEareacauseoflipoproteinglomerulopathy(LPG)[MIM:611771].LPGisanuncommonkidneydiseasecharacterizedbyproteinuria,progressivekidneyfailure,anddistinctivelipoproteinthrombiinglomerularcapillaries.ItmainlyaffectspeopleofJapaneseandChineseorigin.ThedisorderhasrarelybeendescribedinCaucasians.
Similarity:BelongstotheapolipoproteinA1/A4/Efamily.
Databaselinks:UniProtKB/Swiss-Prot:P02649
ApoE是在肝脏中合成的极低密度脂蛋白的组分，也是在细胞间转运胆固醇的高密度脂蛋白的一种亚类.