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Protein

Apolipoprotein E

Gene

APOE

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • amyloid-beta binding Source: UniProtKB
  • antioxidant activity Source: BHF-UCL
  • 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 dimerization activity Source: ARUK-UCL
  • protein homodimerization activity Source: ARUK-UCL
  • structural molecule activity Source: ARUK-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
  • amyloid precursor protein metabolic process Source: UniProtKB
  • artery morphogenesis Source: Ensembl
  • cellular calcium ion homeostasis Source: Ensembl
  • cellular protein metabolic process Source: Reactome
  • 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 assembly Source: Reactome
  • chylomicron remnant clearance Source: BHF-UCL
  • chylomicron remodeling Source: Reactome
  • 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
  • locomotory exploration behavior Source: ARUK-UCL
  • long-chain fatty acid transport Source: Alzheimers_University_of_Toronto
  • long-term memory Source: ARUK-UCL
  • low-density lipoprotein particle remodeling Source: Ensembl
  • maintenance of location in cell Source: Ensembl
  • negative regulation of amyloid-beta 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: ARUK-UCL
  • negative regulation of cellular protein metabolic process Source: ARUK-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 gene expression Source: ARUK-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 long-term synaptic potentiation Source: ARUK-UCL
  • 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 neuron projection development Source: ARUK-UCL
  • 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
  • negative regulation of triglyceride metabolic process Source: Ensembl
  • 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 amyloid-beta formation Source: Alzheimers_University_of_Toronto
  • positive regulation of amyloid fibril formation Source: ARUK-UCL
  • 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 endocytosis Source: ARUK-UCL
  • positive regulation of heparan sulfate binding Source: ARUK-UCL
  • positive regulation of heparan sulfate proteoglycan binding Source: ARUK-UCL
  • 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 neuron projection development Source: ARUK-UCL
  • 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
  • post-translational protein modification Source: Reactome
  • protein import Source: Alzheimers_University_of_Toronto
  • receptor-mediated endocytosis Source: BHF-UCL
  • regulation of amyloid-beta clearance Source: Alzheimers_University_of_Toronto
  • regulation of amyloid fibril formation Source: ARUK-UCL
  • regulation of axon extension Source: UniProtKB
  • regulation of behavioral fear response Source: ARUK-UCL
  • regulation of Cdc42 protein signal transduction Source: BHF-UCL
  • regulation of cellular response to very-low-density lipoprotein particle stimulus Source: ARUK-UCL
  • regulation of cholesterol metabolic process Source: ARUK-UCL
  • regulation of neuronal synaptic plasticity Source: UniProtKB
  • regulation of neuron death Source: Alzheimers_University_of_Toronto
  • regulation of protein homooligomerization Source: ARUK-UCL
  • regulation of protein metabolic process Source: ARUK-UCL
  • regulation of tau-protein kinase activity Source: Alzheimers_University_of_Toronto
  • regulation of transcription by RNA polymerase II Source: Reactome
  • response to caloric restriction Source: ARUK-UCL
  • 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

Keywordsi

Molecular functionHeparin-binding
Biological processCholesterol metabolism, Lipid metabolism, Lipid transport, Steroid metabolism, Sterol metabolism, Transport

Enzyme and pathway databases

ReactomeiR-HSA-3000480 Scavenging by Class A Receptors
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors
R-HSA-8957275 Post-translational protein phosphorylation
R-HSA-8963888 Chylomicron assembly
R-HSA-8963901 Chylomicron remodeling
R-HSA-8964026 Chylomicron clearance
R-HSA-8964058 HDL remodeling
R-HSA-975634 Retinoid metabolism and transport
SIGNORiP02649

Protein family/group databases

MoonDBiP02649 Predicted

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

EuPathDBiHostDB:ENSG00000130203.9
HGNCiHGNC:613 APOE
MIMi107741 gene
neXtProtiNX_P02649

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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:617347
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00064631E → K in HLPP3; form E4 Philadelphia and form E5-type; only form E4 Philadelphia is associated with HLPP3. 1 PublicationCorresponds to variant dbSNP:rs201672011EnsemblClinVar.1
Natural variantiVAR_000654145G → GEVQAMLG in HLPP3; form E3 Leiden. 1 Publication1
Natural variantiVAR_000657154R → C in HLPP3; form E2-type. Corresponds to variant dbSNP:rs121918393EnsemblClinVar.1
Natural variantiVAR_000656154R → S in HLPP3; form E2 Christchurch. 2 PublicationsCorresponds to variant dbSNP:rs121918393EnsemblClinVar.1
Natural variantiVAR_000658160R → C in HLPP3; form E3**. 1 PublicationCorresponds to variant dbSNP:rs387906567EnsemblClinVar.1
Natural variantiVAR_000662164K → E in HLPP3; form E1 Harrisburg. Corresponds to variant dbSNP:rs121918394EnsemblClinVar.1
Natural variantiVAR_000661164K → Q in HLPP3; form E2**. Corresponds to variant dbSNP:rs121918394EnsemblClinVar.1
Natural variantiVAR_000664176R → C in HLPP3; forms E1 Weisgraber, form E2 and form E3**; form E3** is associated with HLPP. 3 PublicationsCorresponds to variant dbSNP:rs7412EnsemblClinVar.1
Natural variantiVAR_000668262 – 263EE → KK in HLPP3; form E7 Suita. 2
Alzheimer disease 2 (AD2)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry. The APOE*4 allele (APOE form E4) 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.1 Publication
Disease descriptionA late-onset form of Alzheimer disease. Alzheimer disease is a 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 constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, 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
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 dbSNP:rs121918399EnsemblClinVar.1
Natural variantiVAR_042735163R → P in LPG; form E2 Sendai. 1 PublicationCorresponds to variant dbSNP:rs121918397EnsemblClinVar.1
Familial hypercholesterolemia (FH)3 Publications
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA common autosomal dominant disorder characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. The disorder occurs in 2 clinical forms: a mild form that becomes evident in the fourth or fifth decade in individuals carrying heterozygous LDLR mutations; a more severe form that usually manifests in the first two decades of life in individuals with homozygous LDLR mutations.
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 dbSNP:rs769452EnsemblClinVar.1
Natural variantiVAR_000653145G → D in FH; unknown pathological significance; form E1 Weisgraber. 2 PublicationsCorresponds to variant dbSNP:rs267606664EnsemblClinVar.1

Keywords - Diseasei

Alzheimer disease, Amyloidosis, Disease mutation, Hyperlipidemia, Neurodegeneration

Organism-specific databases

DisGeNETi348
MalaCardsiAPOE
MIMi104310 phenotype
143890 phenotype
269600 phenotype
611771 phenotype
617347 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...) threonine1 Publication1
Glycosylationi36O-linked (GalNAc...) threonine1 Publication1
Glycosylationi93N-linked (Glc) (glycation) lysine1
Modified residuei143Methionine sulfoxideBy similarity1
Modified residuei147Phosphoserine; by FAM20CCombined sources1 Publication1
Glycosylationi212O-linked (GalNAc...) threonine1 Publication1
Glycosylationi307O-linked (GalNAc...) threonine1 Publication1
Glycosylationi308O-linked (GalNAc...) serine1 Publication1
Glycosylationi314O-linked (GalNAc...) serine1 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
ProteomicsDBi51537

2D gel databases

DOSAC-COBS-2DPAGEiP02649
SWISS-2DPAGEiP02649

PTM databases

CarbonylDBiP02649
GlyConnecti648
iPTMnetiP02649
PhosphoSitePlusiP02649
SwissPalmiP02649
UniCarbKBiP02649

Miscellaneous databases

PMAP-CutDBiP02649

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

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi106845, 63 interactors
DIPiDIP-1120N
IntActiP02649, 33 interactors
MINTiP02649
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[»]
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

InterProiView protein in InterPro
IPR000074 ApoA_E
PfamiView protein in Pfam
PF01442 Apolipoprotein, 1 hit

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 dbSNP:rs121918392EnsemblClinVar.1
Natural variantiVAR_00064631E → K in HLPP3; form E4 Philadelphia and form E5-type; only form E4 Philadelphia is associated with HLPP3. 1 PublicationCorresponds to variant dbSNP:rs201672011EnsemblClinVar.1
Natural variantiVAR_04273443R → C in LPG; form E2 Kyoto. 2 PublicationsCorresponds to variant dbSNP:rs121918399EnsemblClinVar.1
Natural variantiVAR_00064746L → P in FH; unknown pathological significance; form E4 Freiburg. 2 PublicationsCorresponds to variant dbSNP:rs769452EnsemblClinVar.1
Natural variantiVAR_00064860T → A in form E3 Freiburg. Corresponds to variant dbSNP:rs28931576EnsemblClinVar.1
Natural variantiVAR_01411464Q → H Polymorphism; confirmed at protein level. 2 PublicationsCorresponds to variant dbSNP:rs370594287Ensembl.1
Natural variantiVAR_00064999Q → K in form E5 Frankfurt. 1
Natural variantiVAR_000650102P → R in form E5-type; no hyperlipidemia. Corresponds to variant dbSNP:rs28931578EnsemblClinVar.1
Natural variantiVAR_000651117A → T in form E3*. Corresponds to variant dbSNP:rs28931577EnsemblClinVar.1
Natural variantiVAR_016789124A → V in form E3 Basel. 1 PublicationCorresponds to variant dbSNP:rs937063425Ensembl.1
Natural variantiVAR_000652130C → R in HLPP3 and AD2; form E3**, form E4, form E4/3 and some forms E5-type; form E3** is associated with HLPP3; form E4 is associated with AD2. 5 PublicationsCorresponds to variant dbSNP:rs429358EnsemblClinVar.1
Natural variantiVAR_000653145G → D in FH; unknown pathological significance; form E1 Weisgraber. 2 PublicationsCorresponds to variant dbSNP:rs267606664EnsemblClinVar.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 dbSNP:rs28931578EnsemblClinVar.1
Natural variantiVAR_000657154R → C in HLPP3; form E2-type. Corresponds to variant dbSNP:rs121918393EnsemblClinVar.1
Natural variantiVAR_000656154R → S in HLPP3; form E2 Christchurch. 2 PublicationsCorresponds to variant dbSNP:rs121918393EnsemblClinVar.1
Natural variantiVAR_000658160R → C in HLPP3; form E3**. 1 PublicationCorresponds to variant dbSNP:rs387906567EnsemblClinVar.1
Natural variantiVAR_000659163R → C in HLPP3 and FH; form E4 Philadelphia and form E2-type. 3 PublicationsCorresponds to variant dbSNP:rs769455EnsemblClinVar.1
Natural variantiVAR_000660163R → H in E3 Kochi. Corresponds to variant dbSNP:rs121918397EnsemblClinVar.1
Natural variantiVAR_042735163R → P in LPG; form E2 Sendai. 1 PublicationCorresponds to variant dbSNP:rs121918397EnsemblClinVar.1
Natural variantiVAR_000662164K → E in HLPP3; form E1 Harrisburg. Corresponds to variant dbSNP:rs121918394EnsemblClinVar.1
Natural variantiVAR_000661164K → Q in HLPP3; form E2**. Corresponds to variant dbSNP:rs121918394EnsemblClinVar.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 dbSNP:rs267606662EnsemblClinVar.1
Natural variantiVAR_000664176R → C in HLPP3; forms E1 Weisgraber, form E2 and form E3**; form E3** is associated with HLPP. 3 PublicationsCorresponds to variant dbSNP:rs7412EnsemblClinVar.1
Natural variantiVAR_000665242R → Q in form E2 Fukuoka. Corresponds to variant dbSNP:rs267606663EnsemblClinVar.1
Natural variantiVAR_000666246R → C in form E2 Dunedin. Corresponds to variant dbSNP:rs121918395EnsemblClinVar.1
Natural variantiVAR_000667254V → E in form E2 WG. 1 PublicationCorresponds to variant dbSNP:rs199768005EnsemblClinVar.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 dbSNP:rs267606661EnsemblClinVar.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 dbSNP:rs121918398EnsemblClinVar.1
Natural variantiVAR_000672314S → R in form E4 HG. 1 PublicationCorresponds to variant dbSNP:rs28931579EnsemblClinVar.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

Similar proteinsi

Entry informationi

Entry nameiAPOE_HUMAN
AccessioniPrimary (citable) accession number: P02649
Secondary accession number(s): B2RC15, C0JYY5, Q9P2S4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: June 20, 2018
This is version 232 of the entry and version 1 of the sequence. See 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

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