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Protein

Apolipoprotein E

Gene

APOE

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues.1 Publication

GO - Molecular functioni

  • antioxidant activity Source: BHF-UCL
  • beta-amyloid binding Source: UniProtKB
  • cholesterol binding Source: GO_Central
  • cholesterol transporter activity Source: GO_Central
  • heparin binding Source: BHF-UCL
  • identical protein binding Source: BHF-UCL
  • lipid binding Source: UniProtKB
  • lipid transporter activity Source: BHF-UCL
  • lipoprotein particle binding Source: Ensembl
  • low-density lipoprotein particle receptor binding Source: BHF-UCL
  • metal chelating activity Source: BHF-UCL
  • phosphatidylcholine-sterol O-acyltransferase activator activity Source: BHF-UCL
  • phospholipid binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • tau protein binding Source: BHF-UCL
  • very-low-density lipoprotein particle receptor binding Source: BHF-UCL

GO - Biological processi

  • AMPA glutamate receptor clustering Source: Alzheimers_University_of_Toronto
  • artery morphogenesis Source: Ensembl
  • cellular calcium ion homeostasis Source: Ensembl
  • cGMP-mediated signaling Source: BHF-UCL
  • cholesterol catabolic process Source: GO_Central
  • cholesterol efflux Source: BHF-UCL
  • cholesterol homeostasis Source: BHF-UCL
  • cholesterol metabolic process Source: BHF-UCL
  • chylomicron remnant clearance Source: BHF-UCL
  • cytoskeleton organization Source: UniProtKB
  • fatty acid homeostasis Source: Alzheimers_University_of_Toronto
  • G-protein coupled receptor signaling pathway Source: BHF-UCL
  • high-density lipoprotein particle assembly Source: BHF-UCL
  • high-density lipoprotein particle clearance Source: BHF-UCL
  • high-density lipoprotein particle remodeling Source: BHF-UCL
  • intracellular transport Source: UniProtKB
  • lipid transport involved in lipid storage Source: BHF-UCL
  • lipoprotein biosynthetic process Source: Ensembl
  • lipoprotein catabolic process Source: GO_Central
  • lipoprotein metabolic process Source: Reactome
  • long-chain fatty acid transport Source: Alzheimers_University_of_Toronto
  • low-density lipoprotein particle remodeling Source: Ensembl
  • maintenance of location in cell Source: Ensembl
  • negative regulation of beta-amyloid formation Source: Alzheimers_University_of_Toronto
  • negative regulation of blood coagulation Source: BHF-UCL
  • negative regulation of blood vessel endothelial cell migration Source: BHF-UCL
  • negative regulation of canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • negative regulation of cholesterol biosynthetic process Source: BHF-UCL
  • negative regulation of cholesterol efflux Source: Alzheimers_University_of_Toronto
  • negative regulation of dendritic spine development Source: Alzheimers_University_of_Toronto
  • negative regulation of dendritic spine maintenance Source: Alzheimers_University_of_Toronto
  • negative regulation of endothelial cell proliferation Source: BHF-UCL
  • negative regulation of inflammatory response Source: BHF-UCL
  • negative regulation of lipid biosynthetic process Source: Alzheimers_University_of_Toronto
  • negative regulation of lipid transport across blood brain barrier Source: Alzheimers_University_of_Toronto
  • negative regulation of MAP kinase activity Source: BHF-UCL
  • negative regulation of neuron apoptotic process Source: GO_Central
  • negative regulation of neuron death Source: Alzheimers_University_of_Toronto
  • negative regulation of phospholipid efflux Source: Alzheimers_University_of_Toronto
  • negative regulation of platelet activation Source: BHF-UCL
  • negative regulation of postsynaptic membrane organization Source: Alzheimers_University_of_Toronto
  • negative regulation of presynaptic membrane organization Source: Alzheimers_University_of_Toronto
  • neuron projection regeneration Source: GO_Central
  • nitric oxide mediated signal transduction Source: BHF-UCL
  • NMDA glutamate receptor clustering Source: Alzheimers_University_of_Toronto
  • phospholipid efflux Source: BHF-UCL
  • positive regulation by host of viral process Source: AgBase
  • positive regulation of beta-amyloid formation Source: Alzheimers_University_of_Toronto
  • positive regulation of cGMP biosynthetic process Source: BHF-UCL
  • positive regulation of cholesterol efflux Source: Alzheimers_University_of_Toronto
  • positive regulation of cholesterol esterification Source: BHF-UCL
  • positive regulation of dendritic spine development Source: Alzheimers_University_of_Toronto
  • positive regulation of dendritic spine maintenance Source: Alzheimers_University_of_Toronto
  • positive regulation of lipid biosynthetic process Source: Alzheimers_University_of_Toronto
  • positive regulation of lipid transport across blood brain barrier Source: Alzheimers_University_of_Toronto
  • positive regulation of low-density lipoprotein particle receptor catabolic process Source: BHF-UCL
  • positive regulation of membrane protein ectodomain proteolysis Source: BHF-UCL
  • positive regulation of neurofibrillary tangle assembly Source: Alzheimers_University_of_Toronto
  • positive regulation of neuron death Source: Alzheimers_University_of_Toronto
  • positive regulation of nitric-oxide synthase activity Source: BHF-UCL
  • positive regulation of phospholipid efflux Source: Alzheimers_University_of_Toronto
  • positive regulation of postsynaptic membrane organization Source: Alzheimers_University_of_Toronto
  • positive regulation of presynaptic membrane organization Source: Alzheimers_University_of_Toronto
  • protein import Source: Alzheimers_University_of_Toronto
  • receptor-mediated endocytosis Source: BHF-UCL
  • regulation of axon extension Source: UniProtKB
  • regulation of beta-amyloid clearance Source: Alzheimers_University_of_Toronto
  • regulation of Cdc42 protein signal transduction Source: BHF-UCL
  • regulation of gene expression Source: Ensembl
  • regulation of neuronal synaptic plasticity Source: UniProtKB
  • regulation of neuron death Source: Alzheimers_University_of_Toronto
  • regulation of tau-protein kinase activity Source: Alzheimers_University_of_Toronto
  • response to dietary excess Source: Ensembl
  • response to reactive oxygen species Source: UniProtKB
  • retinoid metabolic process Source: Reactome
  • reverse cholesterol transport Source: BHF-UCL
  • synaptic transmission, cholinergic Source: UniProtKB
  • triglyceride catabolic process Source: GO_Central
  • triglyceride homeostasis Source: BHF-UCL
  • triglyceride metabolic process Source: BHF-UCL
  • vasodilation Source: Ensembl
  • very-low-density lipoprotein particle clearance Source: BHF-UCL
  • very-low-density lipoprotein particle remodeling Source: BHF-UCL
  • virion assembly Source: AgBase
Complete GO annotation...

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Lipid transport, Steroid metabolism, Sterol metabolism, Transport

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000130203-MONOMER.
ReactomeiR-HSA-174800. Chylomicron-mediated lipid transport.
R-HSA-194223. HDL-mediated lipid transport.
R-HSA-3000480. Scavenging by Class A Receptors.
R-HSA-8864260. Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors.
R-HSA-975634. Retinoid metabolism and transport.
SIGNORiP02649.

Names & Taxonomyi

Protein namesi
Recommended name:
Apolipoprotein E
Short name:
Apo-E
Gene namesi
Name:APOE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:613. APOE.

Subcellular locationi

  • Secreted 1 Publication

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • chylomicron Source: BHF-UCL
  • cytoplasm Source: UniProtKB
  • dendrite Source: BHF-UCL
  • early endosome Source: Reactome
  • endocytic vesicle lumen Source: Reactome
  • endoplasmic reticulum Source: AgBase
  • extracellular exosome Source: UniProtKB
  • extracellular matrix Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • extracellular vesicle Source: UniProtKB
  • Golgi apparatus Source: AgBase
  • high-density lipoprotein particle Source: BHF-UCL
  • intermediate-density lipoprotein particle Source: BHF-UCL
  • low-density lipoprotein particle Source: BHF-UCL
  • membrane Source: UniProtKB
  • neuronal cell body Source: BHF-UCL
  • nucleus Source: UniProtKB
  • plasma membrane Source: Reactome
  • very-low-density lipoprotein particle Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Chylomicron, HDL, Secreted, VLDL

Pathology & Biotechi

Involvement in diseasei

Hyperlipoproteinemia 3 (HLPP3)4 Publications
The disease is caused by mutations affecting the gene represented in this entry. The vast majority of the patients are homozygous for APOE*2 alleles. More severe cases of HLPP3 have also been observed in individuals heterozygous for rare APOE variants. The influence of APOE on lipid levels is often suggested to have major implications for the risk of coronary artery disease (CAD). Individuals carrying the common APOE*4 variant are at higher risk of CAD.
Disease descriptionA disorder characterized by the accumulation of intermediate-density lipoprotein particles (IDL or broad-beta-lipoprotein) rich in cholesterol. Clinical features include xanthomas, yellowish lipid deposits in the palmar crease, or less specific on tendons and on elbows. The disorder rarely manifests before the third decade in men. In women, it is usually expressed only after the menopause.
See also OMIM:107741
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00064631E → K in HLPP3; form E4 Philadelphia and form E5-type; only form E4 Philadelphia is disease-linked. 1 PublicationCorresponds to variant rs201672011dbSNPEnsembl.1
Natural variantiVAR_000652130C → R in HLPP3; form E3**, form E4, form E4/3 and some forms E5-type; only form E3** is disease-linked. 4 PublicationsCorresponds to variant rs429358dbSNPEnsembl.1
Natural variantiVAR_000654145G → GEVQAMLG in HLPP3; form E3 Leiden. 1 Publication1
Natural variantiVAR_000657154R → C in HLPP3; form E2-type. Corresponds to variant rs121918393dbSNPEnsembl.1
Natural variantiVAR_000656154R → S in HLPP3; form E2 Christchurch. 2 PublicationsCorresponds to variant rs121918393dbSNPEnsembl.1
Natural variantiVAR_000658160R → C in HLPP3; form E3**. 1 PublicationCorresponds to variant rs387906567dbSNPEnsembl.1
Natural variantiVAR_000659163R → C in HLPP3 and FH; form E4 Philadelphia and form E2-type. 3 PublicationsCorresponds to variant rs769455dbSNPEnsembl.1
Natural variantiVAR_000662164K → E in HLPP3; form E1 Harrisburg. Corresponds to variant rs121918394dbSNPEnsembl.1
Natural variantiVAR_000661164K → Q in HLPP3; form E2**. Corresponds to variant rs121918394dbSNPEnsembl.1
Natural variantiVAR_000664176R → C in HLPP3; forms E1 Weisgraber, form E2 and form E3**. 3 PublicationsCorresponds to variant rs7412dbSNPEnsembl.1
Natural variantiVAR_000668262 – 263EE → KK in HLPP3; form E7 Suita. 2
Alzheimer disease 2 (AD2)
Disease susceptibility is associated with variations affecting the gene represented in this entry. The APOE*4 allele is genetically associated with the common late onset familial and sporadic forms of Alzheimer disease. Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE*4 alleles in 42 families with late onset AD. Thus APOE*4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE*4 was virtually sufficient to cause AD by age 80. The mechanism by which APOE*4 participates in pathogenesis is not known.
Disease descriptionA late-onset neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.
See also OMIM:104310
Sea-blue histiocyte disease (SBHD)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCharacterized by splenomegaly, mild thrombocytopenia and, in the bone marrow, numerous histiocytes containing cytoplasmic granules which stain bright blue with the usual hematologic stains. The syndrome is the consequence of an inherited metabolic defect analogous to Gaucher disease and other sphingolipidoses.
See also OMIM:269600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035015167Missing in SBHD and FH; also found in patients with a diagnosis of familial combined hyperlipidemia. 6 Publications1
Lipoprotein glomerulopathy (LPG)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionUncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries.
See also OMIM:611771
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04273443R → C in LPG; form E2 Kyoto. 2 PublicationsCorresponds to variant rs121918399dbSNPEnsembl.1
Natural variantiVAR_042735163R → P in LPG; form E2 Sendai. 1 PublicationCorresponds to variant rs121918397dbSNPEnsembl.1
Familial hypercholesterolemia (FH)3 Publications
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionCommon autosomal semi-dominant disease that affects about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis).
See also OMIM:143890
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00064746L → P in FH; unknown pathological significance; form E4 Freiburg. 2 PublicationsCorresponds to variant rs769452dbSNPEnsembl.1
Natural variantiVAR_000653145G → D in FH; unknown pathological significance; form E1 Weisgraber. 2 PublicationsCorresponds to variant rs267606664dbSNPEnsembl.1
Natural variantiVAR_000659163R → C in HLPP3 and FH; form E4 Philadelphia and form E2-type. 3 PublicationsCorresponds to variant rs769455dbSNPEnsembl.1
Natural variantiVAR_035015167Missing in SBHD and FH; also found in patients with a diagnosis of familial combined hyperlipidemia. 6 Publications1

Keywords - Diseasei

Alzheimer disease, Amyloidosis, Disease mutation, Hyperlipidemia, Neurodegeneration

Organism-specific databases

DisGeNETi348.
MalaCardsiAPOE.
MIMi104310. phenotype.
107741. gene+phenotype.
143890. phenotype.
269600. phenotype.
611771. phenotype.
OpenTargetsiENSG00000130203.
Orphaneti238616. Alzheimer disease.
1648. Dementia with Lewy body.
406. Heterozygous familial hypercholesterolemia.
412. Hyperlipoproteinemia type 3.
329481. Lipoprotein glomerulopathy.
158029. Sea-blue histiocytosis.
PharmGKBiPA55.

Chemistry databases

DrugBankiDB00062. Human Serum Albumin.
DB00064. Serum albumin iodonated.

Polymorphism and mutation databases

BioMutaiAPOE.
DMDMi114039.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 181 PublicationAdd BLAST18
ChainiPRO_000000198719 – 317Apolipoprotein EAdd BLAST299

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi26O-linked (GalNAc...)1 Publication1
Glycosylationi36O-linked (GalNAc...)1 Publication1
Glycosylationi93N-linked (Glc) (glycation)1
Modified residuei143Methionine sulfoxideBy similarity1
Modified residuei147Phosphoserine; by FAM20CCombined sources1 Publication1
Glycosylationi212O-linked (GalNAc...)1 Publication1
Glycosylationi307O-linked (GalNAc...)1 Publication1
Glycosylationi308O-linked (GalNAc...)1 Publication1
Glycosylationi314O-linked (GalNAc...)1 Publication1

Post-translational modificationi

Synthesized with the sialic acid attached by O-glycosidic linkage and is subsequently desialylated in plasma. O-glycosylated with core 1 or possibly core 8 glycans. Thr-307 and Ser-314 are minor glycosylation sites compared to Ser-308.2 Publications
Glycated in plasma VLDL of normal subjects, and of hyperglycemic diabetic patients at a higher level (2-3 fold).
Phosphorylated by FAM20C in the extracellular medium.1 Publication

Keywords - PTMi

Glycation, Glycoprotein, Oxidation, Phosphoprotein

Proteomic databases

EPDiP02649.
MaxQBiP02649.
PaxDbiP02649.
PeptideAtlasiP02649.
PRIDEiP02649.

2D gel databases

DOSAC-COBS-2DPAGEP02649.
SWISS-2DPAGEP02649.

PTM databases

iPTMnetiP02649.
PhosphoSitePlusiP02649.
SwissPalmiP02649.
UniCarbKBiP02649.

Miscellaneous databases

PMAP-CutDBP02649.

Expressioni

Tissue specificityi

Occurs in all lipoprotein fractions in plasma. It constitutes 10-20% of very low density lipoproteins (VLDL) and 1-2% of high density lipoproteins (HDL). APOE is produced in most organs. Significant quantities are produced in liver, brain, spleen, lung, adrenal, ovary, kidney and muscle.

Gene expression databases

BgeeiENSG00000130203.
CleanExiHS_APOE.
ExpressionAtlasiP02649. baseline and differential.
GenevisibleiP02649. HS.

Organism-specific databases

HPAiCAB008363.
CAB069921.
HPA065539.
HPA068768.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
P279584EBI-1222467,EBI-6904269From a different organism.
CDC37Q165433EBI-1222467,EBI-295634
ECSITQ9BQ954EBI-1222467,EBI-712452
HPP007387EBI-1222467,EBI-1220767
LDLRP011302EBI-1222467,EBI-988319
LRP8Q141142EBI-1222467,EBI-2681187
MAPTP106363EBI-9209835,EBI-366182
PDCD4Q53EL63EBI-1222467,EBI-935824
ST13P505023EBI-1222467,EBI-357285
TMCC2O750695EBI-1222467,EBI-726731

GO - Molecular functioni

  • identical protein binding Source: BHF-UCL
  • low-density lipoprotein particle receptor binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • tau protein binding Source: BHF-UCL
  • very-low-density lipoprotein particle receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi106845. 58 interactors.
DIPiDIP-1120N.
IntActiP02649. 31 interactors.
MINTiMINT-4999641.
STRINGi9606.ENSP00000252486.

Structurei

Secondary structure

1317
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi22 – 24Combined sources3
Helixi31 – 39Combined sources9
Turni40 – 42Combined sources3
Helixi43 – 60Combined sources18
Helixi63 – 70Combined sources8
Helixi73 – 96Combined sources24
Turni97 – 99Combined sources3
Helixi106 – 141Combined sources36
Turni143 – 145Combined sources3
Helixi149 – 179Combined sources31
Turni180 – 182Combined sources3
Turni187 – 190Combined sources4
Helixi193 – 198Combined sources6
Beta strandi200 – 202Combined sources3
Helixi209 – 217Combined sources9
Helixi228 – 241Combined sources14
Helixi257 – 283Combined sources27
Helixi286 – 303Combined sources18
Beta strandi307 – 309Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B68X-ray2.00A19-209[»]
1BZ4X-ray1.85A40-183[»]
1EA8X-ray1.95A19-209[»]
1GS9X-ray1.70A19-183[»]
1H7IX-ray1.90A19-209[»]
1LE2X-ray3.00A41-184[»]
1LE4X-ray2.50A41-184[»]
1LPEX-ray2.25A41-184[»]
1NFNX-ray1.80A19-209[»]
1NFOX-ray2.00A19-209[»]
1OEFNMR-A281-304[»]
1OEGNMR-A285-307[»]
1OR2X-ray2.50A19-183[»]
1OR3X-ray1.73A19-183[»]
2KC3NMR-A19-201[»]
2KNYNMR-A147-167[»]
2L7BNMR-A19-317[»]
DisProtiDP00355.
ProteinModelPortaliP02649.
SMRiP02649.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP02649.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati80 – 1011Add BLAST22
Repeati102 – 1232Add BLAST22
Repeati124 – 1453Add BLAST22
Repeati146 – 1674Add BLAST22
Repeati168 – 1895Add BLAST22
Repeati190 – 2116Add BLAST22
Repeati212 – 2337Add BLAST22
Repeati234 – 2558Add BLAST22

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni80 – 2558 X 22 AA approximate tandem repeatsAdd BLAST176
Regioni158 – 168LDL receptor binding1 PublicationAdd BLAST11
Regioni162 – 165Heparin-binding1 Publication4
Regioni229 – 236Heparin-binding1 Publication8

Sequence similaritiesi

Belongs to the apolipoprotein A1/A4/E family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IVK0. Eukaryota.
ENOG4111MYC. LUCA.
GeneTreeiENSGT00730000111315.
HOGENOMiHOG000034006.
HOVERGENiHBG010582.
InParanoidiP02649.
KOiK04524.
OMAiMGSRTRD.
OrthoDBiEOG091G0IA5.
PhylomeDBiP02649.
TreeFamiTF334458.

Family and domain databases

InterProiIPR000074. ApoA_E.
[Graphical view]
PfamiPF01442. Apolipoprotein. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P02649-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKVLWAALLV TFLAGCQAKV EQAVETEPEP ELRQQTEWQS GQRWELALGR
60 70 80 90 100
FWDYLRWVQT LSEQVQEELL SSQVTQELRA LMDETMKELK AYKSELEEQL
110 120 130 140 150
TPVAEETRAR LSKELQAAQA RLGADMEDVC GRLVQYRGEV QAMLGQSTEE
160 170 180 190 200
LRVRLASHLR KLRKRLLRDA DDLQKRLAVY QAGAREGAER GLSAIRERLG
210 220 230 240 250
PLVEQGRVRA ATVGSLAGQP LQERAQAWGE RLRARMEEMG SRTRDRLDEV
260 270 280 290 300
KEQVAEVRAK LEEQAQQIRL QAEAFQARLK SWFEPLVEDM QRQWAGLVEK
310
VQAAVGTSAA PVPSDNH
Length:317
Mass (Da):36,154
Last modified:July 21, 1986 - v1
Checksum:i91AFC04210A30689
GO

Polymorphismi

Three common APOE alleles have been identified: APOE*2, APOE*3, and APOE*4. The corresponding three major isoforms, E2, E3, and E4, are recognized according to their relative position after isoelectric focusing. Different mutations causing the same migration pattern after isoelectric focusing define different isoform subtypes. The most common isoform is E3 and is present in 40-90% of the population. Common APOE variants influence lipoprotein metabolism in healthy individuals.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00064521E → K in form E5; associated with hyperlipoproteinemia and atherosclerosis. 1 PublicationCorresponds to variant rs121918392dbSNPEnsembl.1
Natural variantiVAR_00064631E → K in HLPP3; form E4 Philadelphia and form E5-type; only form E4 Philadelphia is disease-linked. 1 PublicationCorresponds to variant rs201672011dbSNPEnsembl.1
Natural variantiVAR_04273443R → C in LPG; form E2 Kyoto. 2 PublicationsCorresponds to variant rs121918399dbSNPEnsembl.1
Natural variantiVAR_00064746L → P in FH; unknown pathological significance; form E4 Freiburg. 2 PublicationsCorresponds to variant rs769452dbSNPEnsembl.1
Natural variantiVAR_00064860T → A in form E3 Freiburg. Corresponds to variant rs28931576dbSNPEnsembl.1
Natural variantiVAR_01411464Q → H Polymorphism; confirmed at protein level. 2 PublicationsCorresponds to variant rs370594287dbSNPEnsembl.1
Natural variantiVAR_00064999Q → K in form E5 Frankfurt. 1
Natural variantiVAR_000650102P → R in form E5-type; no hyperlipidemia. Corresponds to variant rs28931578dbSNPEnsembl.1
Natural variantiVAR_000651117A → T in form E3*. Corresponds to variant rs28931577dbSNPEnsembl.1
Natural variantiVAR_016789124A → V in form E3 Basel. 1 Publication1
Natural variantiVAR_000652130C → R in HLPP3; form E3**, form E4, form E4/3 and some forms E5-type; only form E3** is disease-linked. 4 PublicationsCorresponds to variant rs429358dbSNPEnsembl.1
Natural variantiVAR_000653145G → D in FH; unknown pathological significance; form E1 Weisgraber. 2 PublicationsCorresponds to variant rs267606664dbSNPEnsembl.1
Natural variantiVAR_000654145G → GEVQAMLG in HLPP3; form E3 Leiden. 1 Publication1
Natural variantiVAR_000655152R → Q in form E2-type; no hyperlipidemia. Corresponds to variant rs28931578dbSNPEnsembl.1
Natural variantiVAR_000657154R → C in HLPP3; form E2-type. Corresponds to variant rs121918393dbSNPEnsembl.1
Natural variantiVAR_000656154R → S in HLPP3; form E2 Christchurch. 2 PublicationsCorresponds to variant rs121918393dbSNPEnsembl.1
Natural variantiVAR_000658160R → C in HLPP3; form E3**. 1 PublicationCorresponds to variant rs387906567dbSNPEnsembl.1
Natural variantiVAR_000659163R → C in HLPP3 and FH; form E4 Philadelphia and form E2-type. 3 PublicationsCorresponds to variant rs769455dbSNPEnsembl.1
Natural variantiVAR_000660163R → H in E3 Kochi. Corresponds to variant rs121918397dbSNPEnsembl.1
Natural variantiVAR_042735163R → P in LPG; form E2 Sendai. 1 PublicationCorresponds to variant rs121918397dbSNPEnsembl.1
Natural variantiVAR_000662164K → E in HLPP3; form E1 Harrisburg. Corresponds to variant rs121918394dbSNPEnsembl.1
Natural variantiVAR_000661164K → Q in HLPP3; form E2**. Corresponds to variant rs121918394dbSNPEnsembl.1
Natural variantiVAR_035015167Missing in SBHD and FH; also found in patients with a diagnosis of familial combined hyperlipidemia. 6 Publications1
Natural variantiVAR_000663170A → P in form E3*. Corresponds to variant rs267606662dbSNPEnsembl.1
Natural variantiVAR_000664176R → C in HLPP3; forms E1 Weisgraber, form E2 and form E3**. 3 PublicationsCorresponds to variant rs7412dbSNPEnsembl.1
Natural variantiVAR_000665242R → Q in form E2 Fukuoka. Corresponds to variant rs267606663dbSNPEnsembl.1
Natural variantiVAR_000666246R → C in form E2 Dunedin. Corresponds to variant rs121918395dbSNPEnsembl.1
Natural variantiVAR_000667254V → E in form E2 WG. 1 PublicationCorresponds to variant rs199768005dbSNPEnsembl.1
Natural variantiVAR_000668262 – 263EE → KK in HLPP3; form E7 Suita. 2
Natural variantiVAR_000669269R → G in form E3 HB and form E4/3. 2 PublicationsCorresponds to variant rs267606661dbSNPEnsembl.1
Natural variantiVAR_000670270L → E in form E1 HE; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_000671292R → H in form E4 PD. 1 PublicationCorresponds to variant rs121918398dbSNPEnsembl.1
Natural variantiVAR_000672314S → R in form E4 HG. 1 PublicationCorresponds to variant rs28931579dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12529 mRNA. Translation: AAB59518.1.
K00396 mRNA. Translation: AAB59546.1.
M10065 Genomic DNA. Translation: AAB59397.1.
AF050154 Genomic DNA. Translation: AAD02505.1.
AF261279 Genomic DNA. Translation: AAG27089.1.
AK314898 mRNA. Translation: BAG37412.1.
FJ525876 Genomic DNA. Translation: ACN81314.1.
BC003557 mRNA. Translation: AAH03557.1.
AB035149 Genomic DNA. Translation: BAA96080.1.
CCDSiCCDS12647.1.
PIRiA92478. LPHUE.
RefSeqiNP_000032.1. NM_000041.3.
NP_001289617.1. NM_001302688.1.
NP_001289618.1. NM_001302689.1.
NP_001289619.1. NM_001302690.1.
NP_001289620.1. NM_001302691.1.
UniGeneiHs.654439.

Genome annotation databases

EnsembliENST00000252486; ENSP00000252486; ENSG00000130203.
GeneIDi348.
KEGGihsa:348.
UCSCiuc002pab.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

Apolipoprotein E entry

Protein Spotlight

Tangled - Issue 83 of June 2007

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12529 mRNA. Translation: AAB59518.1.
K00396 mRNA. Translation: AAB59546.1.
M10065 Genomic DNA. Translation: AAB59397.1.
AF050154 Genomic DNA. Translation: AAD02505.1.
AF261279 Genomic DNA. Translation: AAG27089.1.
AK314898 mRNA. Translation: BAG37412.1.
FJ525876 Genomic DNA. Translation: ACN81314.1.
BC003557 mRNA. Translation: AAH03557.1.
AB035149 Genomic DNA. Translation: BAA96080.1.
CCDSiCCDS12647.1.
PIRiA92478. LPHUE.
RefSeqiNP_000032.1. NM_000041.3.
NP_001289617.1. NM_001302688.1.
NP_001289618.1. NM_001302689.1.
NP_001289619.1. NM_001302690.1.
NP_001289620.1. NM_001302691.1.
UniGeneiHs.654439.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B68X-ray2.00A19-209[»]
1BZ4X-ray1.85A40-183[»]
1EA8X-ray1.95A19-209[»]
1GS9X-ray1.70A19-183[»]
1H7IX-ray1.90A19-209[»]
1LE2X-ray3.00A41-184[»]
1LE4X-ray2.50A41-184[»]
1LPEX-ray2.25A41-184[»]
1NFNX-ray1.80A19-209[»]
1NFOX-ray2.00A19-209[»]
1OEFNMR-A281-304[»]
1OEGNMR-A285-307[»]
1OR2X-ray2.50A19-183[»]
1OR3X-ray1.73A19-183[»]
2KC3NMR-A19-201[»]
2KNYNMR-A147-167[»]
2L7BNMR-A19-317[»]
DisProtiDP00355.
ProteinModelPortaliP02649.
SMRiP02649.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106845. 58 interactors.
DIPiDIP-1120N.
IntActiP02649. 31 interactors.
MINTiMINT-4999641.
STRINGi9606.ENSP00000252486.

Chemistry databases

DrugBankiDB00062. Human Serum Albumin.
DB00064. Serum albumin iodonated.

PTM databases

iPTMnetiP02649.
PhosphoSitePlusiP02649.
SwissPalmiP02649.
UniCarbKBiP02649.

Polymorphism and mutation databases

BioMutaiAPOE.
DMDMi114039.

2D gel databases

DOSAC-COBS-2DPAGEP02649.
SWISS-2DPAGEP02649.

Proteomic databases

EPDiP02649.
MaxQBiP02649.
PaxDbiP02649.
PeptideAtlasiP02649.
PRIDEiP02649.

Protocols and materials databases

DNASUi348.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000252486; ENSP00000252486; ENSG00000130203.
GeneIDi348.
KEGGihsa:348.
UCSCiuc002pab.4. human.

Organism-specific databases

CTDi348.
DisGeNETi348.
GeneCardsiAPOE.
HGNCiHGNC:613. APOE.
HPAiCAB008363.
CAB069921.
HPA065539.
HPA068768.
MalaCardsiAPOE.
MIMi104310. phenotype.
107741. gene+phenotype.
143890. phenotype.
269600. phenotype.
611771. phenotype.
neXtProtiNX_P02649.
OpenTargetsiENSG00000130203.
Orphaneti238616. Alzheimer disease.
1648. Dementia with Lewy body.
406. Heterozygous familial hypercholesterolemia.
412. Hyperlipoproteinemia type 3.
329481. Lipoprotein glomerulopathy.
158029. Sea-blue histiocytosis.
PharmGKBiPA55.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IVK0. Eukaryota.
ENOG4111MYC. LUCA.
GeneTreeiENSGT00730000111315.
HOGENOMiHOG000034006.
HOVERGENiHBG010582.
InParanoidiP02649.
KOiK04524.
OMAiMGSRTRD.
OrthoDBiEOG091G0IA5.
PhylomeDBiP02649.
TreeFamiTF334458.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000130203-MONOMER.
ReactomeiR-HSA-174800. Chylomicron-mediated lipid transport.
R-HSA-194223. HDL-mediated lipid transport.
R-HSA-3000480. Scavenging by Class A Receptors.
R-HSA-8864260. Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors.
R-HSA-975634. Retinoid metabolism and transport.
SIGNORiP02649.

Miscellaneous databases

ChiTaRSiAPOE. human.
EvolutionaryTraceiP02649.
GeneWikiiApolipoprotein_E.
GenomeRNAii348.
PMAP-CutDBP02649.
PROiP02649.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130203.
CleanExiHS_APOE.
ExpressionAtlasiP02649. baseline and differential.
GenevisibleiP02649. HS.

Family and domain databases

InterProiIPR000074. ApoA_E.
[Graphical view]
PfamiPF01442. Apolipoprotein. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAPOE_HUMAN
AccessioniPrimary (citable) accession number: P02649
Secondary accession number(s): B2RC15, C0JYY5, Q9P2S4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 2, 2016
This is version 216 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.