InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: APOE

Summary

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.

Comments

Interactions

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
DNA-DNA	0
RNA-RNA	0
DNA-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