MGP Database

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MGP000175

UniProt Annotations

Entry Information
Gene Nameapolipoprotein E
Protein Entry
UniProt ID
SpeciesHuman
Comments
Comment typeDescription
DiseaseAlzheimer 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.
DiseaseFamilial 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:0000269|PubMed:22949395}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseHyperlipoproteinemia 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:0000269|PubMed:1674745, ECO:0000269|PubMed:22481068, ECO:0000269|PubMed:2556398, ECO:0000269|PubMed: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.
DiseaseLipoprotein glomerulopathy (LPG) [MIM:611771]: Uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. {ECO:0000269|PubMed:10432380, ECO:0000269|PubMed:18077821, ECO:0000269|PubMed:9176854}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseSea-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:0000269|PubMed:11095479, ECO:0000269|PubMed:16094309}. Note=The disease is caused by mutations affecting the gene represented in this entry.
FunctionMediates 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.
InteractionQ16543:CDC37; NbExp=3; IntAct=EBI-1222467, EBI-295634; Q9BQ95:ECSIT; NbExp=4; IntAct=EBI-1222467, EBI-712452; P00738:HP; NbExp=7; IntAct=EBI-1222467, EBI-1220767; P01130:LDLR; NbExp=2; IntAct=EBI-1222467, EBI-988319; Q14114:LRP8; NbExp=2; IntAct=EBI-1222467, EBI-2681187; P10636:MAPT; NbExp=3; IntAct=EBI-9209835, EBI-366182; Q53EL6:PDCD4; NbExp=3; IntAct=EBI-1222467, EBI-935824; P50502:ST13; NbExp=3; IntAct=EBI-1222467, EBI-357285; O75069:TMCC2; NbExp=5; IntAct=EBI-1222467, EBI-726731;
PolymorphismThree 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.
PtmGlycated in plasma VLDL of normal subjects, and of hyperglycemic diabetic patients at a higher level (2-3 fold).
PtmPhosphorylation sites are present in the extracellular medium.
PtmSynthesized 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 Thr-314 are minor glycosylation siteS compared to Ser-308. {ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:23234360}.
SimilarityBelongs to the apolipoprotein A1/A4/E family. {ECO:0000305}.
Subcellular LocationSecreted.
Tissue SpecificityOccurs 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.
Web ResourceName=Protein Spotlight; Note=Tangled - Issue 83 of June 2007; URL="http://web.expasy.org/spotlight/back_issues/083";
Web ResourceName=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=APOE";
Web ResourceName=Wikipedia; Note=Apolipoprotein E entry; URL="http://en.wikipedia.org/wiki/Apolipoprotein_E";
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