Homo sapiens Protein: APOE
InnateDB Protein IDBP-56809.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol APOE
Protein Name apolipoprotein E
Synonyms AD2; LDLCQ5; LPG;
Species Homo sapiens
Ensembl Protein ENSP00000252486
InnateDB Gene IDBG-56807 (APOE)
Protein Structure
UniProt Annotation
Function 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.
Subcellular Localization Secreted.
Disease Associations Hyperlipoproteinemia 3 (HLPP3) [MIM:107741]: A 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. {ECO:0000269PubMed:1674745, ECO:0000269PubMed:22481068, ECO:0000269PubMed:2556398, ECO:0000269PubMed:8287539}. Note=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.Alzheimer disease 2 (AD2) [MIM:104310]: A 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. Note=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.Sea-blue histiocyte disease (SBHD) [MIM:269600]: Characterized 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. {ECO:0000269PubMed:11095479, ECO:0000269PubMed:16094309}. Note=The disease is caused by mutations affecting the gene represented in this entry.Lipoprotein glomerulopathy (LPG) [MIM:611771]: Uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. {ECO:0000269PubMed:10432380, ECO:0000269PubMed:18077821, ECO:0000269PubMed:9176854}. Note=The disease is caused by mutations affecting the gene represented in this entry.Familial hypercholesterolemia (FH) [MIM:143890]: Common 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). {ECO:0000269PubMed:22949395}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Tissue Specificity 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.
Number of Interactions This gene and/or its encoded proteins are associated with 66 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.
Experimentally validated
Total 66 [view]
Protein-Protein 66 [view]
Protein-DNA 0
Protein-RNA 0
Predicted by orthology
Total 3 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0001540 beta-amyloid binding
GO:0005102 receptor binding
GO:0005319 lipid transporter activity
GO:0005515 protein binding
GO:0005543 phospholipid binding
GO:0008201 heparin binding
GO:0008289 lipid binding
GO:0016209 antioxidant activity
GO:0017127 cholesterol transporter activity
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0046848 hydroxyapatite binding
GO:0046911 metal chelating activity
GO:0048156 tau protein binding
GO:0050750 low-density lipoprotein particle receptor binding
GO:0060228 phosphatidylcholine-sterol O-acyltransferase activator activity
GO:0070326 very-low-density lipoprotein particle receptor binding
GO:0071813 lipoprotein particle binding
Biological Process
GO:0000302 response to reactive oxygen species
GO:0001523 retinoid metabolic process
GO:0001937 negative regulation of endothelial cell proliferation
GO:0002021 response to dietary excess
GO:0006629 lipid metabolic process
GO:0006641 triglyceride metabolic process
GO:0006707 cholesterol catabolic process
GO:0006869 lipid transport
GO:0006874 cellular calcium ion homeostasis
GO:0006898 receptor-mediated endocytosis
GO:0006979 response to oxidative stress
GO:0007010 cytoskeleton organization
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007263 nitric oxide mediated signal transduction
GO:0007271 synaptic transmission, cholinergic
GO:0007568 aging
GO:0007603 phototransduction, visible light
GO:0008203 cholesterol metabolic process
GO:0008219 cell death
GO:0010468 regulation of gene expression
GO:0010544 negative regulation of platelet activation
GO:0010873 positive regulation of cholesterol esterification
GO:0010875 positive regulation of cholesterol efflux
GO:0014012 peripheral nervous system axon regeneration
GO:0015909 long-chain fatty acid transport
GO:0017038 protein import
GO:0019934 cGMP-mediated signaling
GO:0030195 negative regulation of blood coagulation
GO:0030516 regulation of axon extension
GO:0030828 positive regulation of cGMP biosynthetic process
GO:0032489 regulation of Cdc42 protein signal transduction
GO:0032526 response to retinoic acid
GO:0032805 positive regulation of low-density lipoprotein particle receptor catabolic process
GO:0032868 response to insulin
GO:0033344 cholesterol efflux
GO:0033700 phospholipid efflux
GO:0034372 very-low-density lipoprotein particle remodeling
GO:0034374 low-density lipoprotein particle remodeling
GO:0034375 high-density lipoprotein particle remodeling
GO:0034380 high-density lipoprotein particle assembly
GO:0034382 chylomicron remnant clearance
GO:0034384 high-density lipoprotein particle clearance
GO:0034447 very-low-density lipoprotein particle clearance
GO:0042157 lipoprotein metabolic process
GO:0042158 lipoprotein biosynthetic process
GO:0042159 lipoprotein catabolic process
GO:0042311 vasodilation
GO:0042632 cholesterol homeostasis
GO:0043407 negative regulation of MAP kinase activity
GO:0043524 negative regulation of neuron apoptotic process
GO:0043537 negative regulation of blood vessel endothelial cell migration
GO:0043691 reverse cholesterol transport
GO:0044281 small molecule metabolic process
GO:0045471 response to ethanol
GO:0045541 negative regulation of cholesterol biosynthetic process
GO:0045773 positive regulation of axon extension
GO:0046889 positive regulation of lipid biosynthetic process
GO:0046907 intracellular transport
GO:0048168 regulation of neuronal synaptic plasticity
GO:0048709 oligodendrocyte differentiation
GO:0048844 artery morphogenesis
GO:0050728 negative regulation of inflammatory response
GO:0051000 positive regulation of nitric-oxide synthase activity
GO:0051044 positive regulation of membrane protein ectodomain proteolysis
GO:0051055 negative regulation of lipid biosynthetic process
GO:0051651 maintenance of location in cell
GO:0055088 lipid homeostasis
GO:0055089 fatty acid homeostasis
GO:0060999 positive regulation of dendritic spine development
GO:0061000 negative regulation of dendritic spine development
GO:0071347 cellular response to interleukin-1
GO:0071363 cellular response to growth factor stimulus
GO:0071397 cellular response to cholesterol
GO:0072358 cardiovascular system development
GO:0090370 negative regulation of cholesterol efflux
GO:0097113 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor clustering
GO:0097114 N-methyl-D-aspartate receptor clustering
GO:1900221 regulation of beta-amyloid clearance
GO:1901214 regulation of neuron death
GO:1901215 negative regulation of neuron death
GO:1901216 positive regulation of neuron death
GO:1901627 negative regulation of postsynaptic membrane organization
GO:1901628 positive regulation of postsynaptic membrane organization
GO:1901630 negative regulation of presynaptic membrane organization
GO:1901631 positive regulation of presynaptic membrane organization
GO:1902004 positive regulation of beta-amyloid formation
GO:1902430 negative regulation of beta-amyloid formation
GO:1902947 regulation of tau-protein kinase activity
GO:1902951 negative regulation of dendritic spine maintenance
GO:1902952 positive regulation of dendritic spine maintenance
GO:1902995 positive regulation of phospholipid efflux
GO:1902998 positive regulation of neurofibrillary tangle assembly
GO:1902999 negative regulation of phospholipid efflux
GO:1903001 negative regulation of lipid transport across blood brain barrier
GO:1903002 positive regulation of lipid transport across blood brain barrier
Cellular Component
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005634 nucleus
GO:0005635 nuclear envelope
GO:0005737 cytoplasm
GO:0005764 lysosome
GO:0005768 endosome
GO:0005769 early endosome
GO:0005770 late endosome
GO:0005783 endoplasmic reticulum
GO:0005794 Golgi apparatus
GO:0005874 microtubule
GO:0005886 plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0030425 dendrite
GO:0031232 extrinsic component of external side of plasma membrane
GO:0034361 very-low-density lipoprotein particle
GO:0034362 low-density lipoprotein particle
GO:0034363 intermediate-density lipoprotein particle
GO:0034364 high-density lipoprotein particle
GO:0034365 discoidal high-density lipoprotein particle
GO:0042627 chylomicron
GO:0043025 neuronal cell body
GO:0070062 extracellular vesicular exosome
GO:0071682 endocytic vesicle lumen
GO:0072562 blood microparticle
Protein Structure and Domains
InterPro IPR000074 Apolipoprotein A1/A4/E
PFAM PF01442
Post-translational Modifications
SwissProt P02649
PhosphoSite PhosphoSite-P02649
UniProt Splice Variant
Entrez Gene 348
RefSeq NP_000032
OMIM 107741
HPRD 00135
EMBL AB035149 AC011481 AF050154 AF261279 AK314898 BC003557 FJ525876 JX467472 K00396 M10065 M12529 X00199 Z70760
GenPept AAB59397 AAB59518 AAB59546 AAD02505 AAG27089 AAH03557 ACN81314 AFS60672 BAA96080 BAG37412 CAA25017 CAA94806