APOE
entrez
348
canonical
uniprot
P02649
canonical
ensembl
ENSG00000130203
resolver
ensp
ENSP00000252486
resolver
ensp
ENSP00000534877
resolver
ensp
ENSP00000534879
resolver
ensp
ENSP00000534881
resolver
ensp
ENSP00000534885
resolver
ensp
ENSP00000534887
resolver
ensp
ENSP00000534888
resolver
ensp
ENSP00000534893
resolver
ensp
ENSP00000534894
resolver
ensp
ENSP00000534895
resolver
ensp
ENSP00000534896
resolver
ensp
ENSP00000534897
resolver
ensp
ENSP00000534898
resolver
ensp
ENSP00000534899
resolver
ensp
ENSP00000534900
resolver
ensp
ENSP00000534901
resolver
ensp
ENSP00000534902
resolver
ensp
ENSP00000534903
resolver
ensp
ENSP00000534904
resolver
ensp
ENSP00000534905
resolver
ensp
ENSP00000534906
resolver
ensp
ENSP00000534907
resolver
ensp
ENSP00000534908
resolver
enst
ENST00000252486
resolver
enst
ENST00000864817
resolver
enst
ENST00000864820
resolver
enst
ENST00000864822
resolver
enst
ENST00000864826
resolver
enst
ENST00000864828
resolver
enst
ENST00000864829
resolver
enst
ENST00000864834
resolver
enst
ENST00000864835
resolver
enst
ENST00000864836
resolver
enst
ENST00000864837
resolver
enst
ENST00000864838
resolver
enst
ENST00000864839
resolver
enst
ENST00000864840
resolver
enst
ENST00000864841
resolver
enst
ENST00000864842
resolver
enst
ENST00000864843
resolver
enst
ENST00000864844
resolver
enst
ENST00000864845
resolver
enst
ENST00000864846
resolver
enst
ENST00000864847
resolver
enst
ENST00000864848
resolver
enst
ENST00000864849
resolver
genesymbol
APOE
resolver
hgnc
HGNC:613
resolver
uniprot
A0A0S2Z3D5
resolver
uniprot
B2RC15
resolver
uniprot
C0JYY5
resolver
uniprot
Q9P2S4
resolver
uniprot_entry
A0A0S2Z3D5_HUMAN
resolver
uniprot_entry
APOE_HUMAN
resolver
uniprot_sec
B2RC15
resolver
uniprot_sec
C0JYY5
resolver
uniprot_sec
Q9P2S4
resolver
amino_acid_sequence
MKVLWAALLVTFLAGCQAKVEQAVETEPEPELRQQTEWQSGQRWELALGRFWDYLRWVQTLSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQARLGADMEDVCGRLVQYRGEVQAMLGQSTEELRVRLASHLRKLRKRLLRDADDLQKRLAVYQAGAREGAERGLSAIRERLGPLVEQGRVRAATVGSLAGQPLQERAQAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGTSAAPVPSDNH
uniprot
proteins
disease_involvement
DISEASE: Hyperlipoproteinemia 3 (HLPP3) [MIM:617347]: 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:1361196, ECO:0000269|PubMed:1674745, ECO:0000269|PubMed:2101409, ECO:0000269|PubMed:22481068, ECO:0000269|PubMed:2313204, ECO:0000269|PubMed:2556398, ECO:0000269|PubMed:26802169, ECO:0000269|PubMed:2738044, ECO:0000269|PubMed:7635945, ECO:0000269|PubMed:7833947, ECO:0000269|PubMed:8287539}. Note=The disease is caused by variants 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: Alzheimer disease 2 (AD2) [MIM:104310]: A 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. {ECO:0000269|PubMed:10903326, ECO:0000269|PubMed:11258893, ECO:0000269|PubMed:11447277, ECO:0000269|PubMed:28111074, ECO:0000269|PubMed:2987927, ECO:0000269|PubMed:7891887, ECO:0000269|PubMed:7972031, ECO:0000269|PubMed:8071364, ECO:0000269|PubMed:8346443, ECO:0000269|PubMed:8367470, ECO:0000269|PubMed:8939961}. Note=Disease susceptibility is associated with variants 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. {ECO:0000269|PubMed:8346443}.; DISEASE: 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:0000269|PubMed:11095479, ECO:0000269|PubMed:16094309, ECO:0000269|PubMed:22481068, ECO:0000269|PubMed:22949395, ECO:0000269|PubMed:24267230, ECO:0000269|PubMed:26802169}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Lipoprotein 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:10903326, ECO:0000269|PubMed:18077821, ECO:0000269|PubMed:9176854}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:14754908, PubMed:1911868, PubMed:6860692). APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance (PubMed:14754908, PubMed:1911868, PubMed:1917954, PubMed:23620513, PubMed:2762297, PubMed:6860692, PubMed:9395455). Apolipoproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma (PubMed:2762297, PubMed:6860692, PubMed:9395455). As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL) (PubMed:1911868, PubMed:6860692). It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles (PubMed:12950167, PubMed:1530612, PubMed:1917954, PubMed:20030366, PubMed:20303980, PubMed:2063194, PubMed:2762297, PubMed:7635945, PubMed:7768901, PubMed:8756331, PubMed:8939961). Finally, APOE also has a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells (PubMed:23676495, PubMed:7635945, PubMed:9395455, PubMed:9488694). A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes (PubMed:1911868, PubMed:1917954, PubMed:23676495, PubMed:29516132, PubMed:9395455). APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of triglycerides and energy storage in muscle, heart and adipose tissues (PubMed:2762297, PubMed:29516132). By participating in the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis (PubMed:1917954, PubMed:2762297, PubMed:29516132). APOE is also involved in two steps of reverse cholesterol transport, the HDLs-mediated transport of cholesterol from peripheral tissues to the liver, and thereby plays an important role in cholesterol homeostasis (PubMed:14754908, PubMed:23620513, PubMed:9395455). First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues (PubMed:14754908, PubMed:23620513). Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes (PubMed:9395455). APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting (PubMed:25173806, PubMed:8939961). APOE is also involved in innate and adaptive immune responses, controlling for instance the survival of myeloid-derived suppressor cells (By similarity). Binds to the immune cell receptor LILRB4 (PubMed:30333625). APOE may also play a role in transcription regulation through a receptor-dependent and cholesterol-independent mechanism, that activates MAP3K12 and a non-canonical MAPK signal transduction pathway that results in enhanced AP-1-mediated transcription of APP (PubMed:28111074). {ECO:0000250|UniProtKB:P08226, ECO:0000269|PubMed:12950167, ECO:0000269|PubMed:14754908, ECO:0000269|PubMed:1530612, ECO:0000269|PubMed:1911868, ECO:0000269|PubMed:1917954, ECO:0000269|PubMed:20030366, ECO:0000269|PubMed:20303980, ECO:0000269|PubMed:2063194, ECO:0000269|PubMed:23620513, ECO:0000269|PubMed:23676495, ECO:0000269|PubMed:2762297, ECO:0000269|PubMed:28111074, ECO:0000269|PubMed:30333625, ECO:0000269|PubMed:6860692, ECO:0000269|PubMed:7635945, ECO:0000269|PubMed:7768901, ECO:0000269|PubMed:8756331, ECO:0000269|PubMed:8939961, ECO:0000269|PubMed:9395455, ECO:0000269|PubMed:9488694, ECO:0000303|PubMed:25173806, ECO:0000303|PubMed:29516132}.; FUNCTION: (Microbial infection) Through its interaction with HCV envelope glycoprotein E2, participates in the attachment of HCV to HSPGs and other receptors (LDLr, VLDLr, and SR-B1) on the cell surface and to the assembly, maturation and infectivity of HCV viral particles (PubMed:25122793, PubMed:29695434). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (PubMed:29695434). {ECO:0000269|PubMed:25122793, ECO:0000269|PubMed:29695434}.
uniprot
proteins
mass_dalton
36154
uniprot
proteins
mutagenesis
MUTAGEN 79; /note="R->T: Changes the plasma lipoprotein distribution of ApoE4 to the HDL."; /evidence="ECO:0000269|PubMed:8071364"; MUTAGEN 127; /note="E->A: No effect on plasma lipoprotein distribution."; /evidence="ECO:0000269|PubMed:8071364"; MUTAGEN 157; /note="S->R: Increased binding to LDL receptor; when associated with A-167."; /evidence="ECO:0000269|PubMed:2831187"; MUTAGEN 158; /note="H->A: Decreased binding to LDL receptor."; /evidence="ECO:0000269|PubMed:2831187"; MUTAGEN 161; /note="K->A: Decreased binding to LDL receptor."; /evidence="ECO:0000269|PubMed:2831187"; MUTAGEN 162; /note="L->P: Decreased binding to LDL receptor."; /evidence="ECO:0000269|PubMed:2831187"; MUTAGEN 167; /note="L->A: Increased binding to LDL receptor; when associated with R-157."; /evidence="ECO:0000269|PubMed:2831187"; MUTAGEN 168; /note="R->A: Decreased binding to LDL receptor."; /evidence="ECO:0000269|PubMed:2831187"; MUTAGEN 172; /note="D->A: Restores the LDL receptor binding activity of ApoE2."; /evidence="ECO:0000269|PubMed:8756331"; MUTAGEN 212; /note="T->A: Loss of O-glycosylation."; /evidence="ECO:0000269|PubMed:2498325
uniprot
proteins
post_translational_modification
PTM: APOE exists as multiple glycosylated and sialylated glycoforms within cells and in plasma (PubMed:29516132). The extent of glycosylation and sialylation are tissue and context specific (PubMed:29516132). Plasma APOE undergoes desialylation and is less glycosylated and sialylated than the cellular form (PubMed:19838169, PubMed:20511397, PubMed:23234360, PubMed:2498325). Glycosylation is not required for proper expression and secretion (PubMed:2498325). O-glycosylated with core 1 or possibly core 8 glycans. Thr-307 and Ser-314 are minor glycosylation sites compared to Ser-308 (PubMed:19838169, PubMed:23234360). {ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:20511397, ECO:0000269|PubMed:23234360, ECO:0000269|PubMed:2498325, ECO:0000303|PubMed:29516132}.; PTM: Glycated in plasma VLDL of normal subjects, and of hyperglycemic diabetic patients at a higher level (2-3 fold). {ECO:0000269|PubMed:10452964}.; PTM: Phosphorylated by FAM20C in the extracellular medium. {ECO:0000269|PubMed:26091039}.; PTM: Undergoes C-terminal proteolytic processing in neurons. C-terminally truncated APOE has a tendency to form neurotoxic intracellular neurofibrillary tangle-like inclusions in neurons. {ECO:0000269|PubMed:11447277}.
uniprot
proteins
protein_family
Apolipoprotein A1/A4/E family
uniprot
proteins
pubmed
10027417
uniprot
proteins
pubmed
10432380
uniprot
proteins
pubmed
10452964
uniprot
proteins
pubmed
10520737
uniprot
proteins
pubmed
10850798
uniprot
proteins
pubmed
10903326
uniprot
proteins
pubmed
11042151
uniprot
proteins
pubmed
11095479
uniprot
proteins
pubmed
11258893
uniprot
proteins
pubmed
11447277
uniprot
proteins
pubmed
12864777
uniprot
proteins
pubmed
12950167
uniprot
proteins
pubmed
12966036
uniprot
proteins
pubmed
1361196
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14754908
uniprot
proteins
pubmed
1530612
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16094309
uniprot
proteins
pubmed
1674745
uniprot
proteins
pubmed
1713245
uniprot
proteins
pubmed
18077821
uniprot
proteins
pubmed
1911868
uniprot
proteins
pubmed
1917954
uniprot
proteins
pubmed
19838169
uniprot
proteins
pubmed
20030366
uniprot
proteins
pubmed
20303980
uniprot
proteins
pubmed
20511397
uniprot
proteins
pubmed
2063194
uniprot
proteins
pubmed
2101409
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22028381
uniprot
proteins
pubmed
22481068
uniprot
proteins
pubmed
2280190
uniprot
proteins
pubmed
22905912
uniprot
proteins
pubmed
22949395
uniprot
proteins
pubmed
2313204
uniprot
proteins
pubmed
23234360
uniprot
proteins
pubmed
2341812
uniprot
proteins
pubmed
23620513
uniprot
proteins
pubmed
23676495
uniprot
proteins
pubmed
24267230
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
2498325
uniprot
proteins
pubmed
25122793
uniprot
proteins
pubmed
25173806
uniprot
proteins
pubmed
2556398
uniprot
proteins
pubmed
26091039
uniprot
proteins
pubmed
26387950
uniprot
proteins
pubmed
26802169
uniprot
proteins
pubmed
2738044
uniprot
proteins
pubmed
2760009
uniprot
proteins
pubmed
2762297
uniprot
proteins
pubmed
28111074
uniprot
proteins
pubmed
2831187
uniprot
proteins
pubmed
29516132
uniprot
proteins
pubmed
29695434
uniprot
proteins
pubmed
2987927
uniprot
proteins
pubmed
30333625
uniprot
proteins
pubmed
30448281
uniprot
proteins
pubmed
3115992
uniprot
proteins
pubmed
3243553
uniprot
proteins
pubmed
33450186
uniprot
proteins
pubmed
3947350
uniprot
proteins
pubmed
6325438
uniprot
proteins
pubmed
6327682
uniprot
proteins
pubmed
6860692
uniprot
proteins
pubmed
6897404
uniprot
proteins
pubmed
7068630
uniprot
proteins
pubmed
7635945
uniprot
proteins
pubmed
7768901
uniprot
proteins
pubmed
7833947
uniprot
proteins
pubmed
7891887
uniprot
proteins
pubmed
7972031
uniprot
proteins
pubmed
7994571
uniprot
proteins
pubmed
8071364
uniprot
proteins
pubmed
8125051
uniprot
proteins
pubmed
8287539
uniprot
proteins
pubmed
8340399
uniprot
proteins
pubmed
8346443
uniprot
proteins
pubmed
8367470
uniprot
proteins
pubmed
8468528
uniprot
proteins
pubmed
8488843
uniprot
proteins
pubmed
8664327
uniprot
proteins
pubmed
8756331
uniprot
proteins
pubmed
8939961
uniprot
proteins
pubmed
9176854
uniprot
proteins
pubmed
9360638
uniprot
proteins
pubmed
9395455
uniprot
proteins
pubmed
9488694
uniprot
proteins
sequence_length
317
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2498325, ECO:0000269|PubMed:30333625}. Secreted, extracellular space {ECO:0000269|PubMed:8340399}. Secreted, extracellular space, extracellular matrix {ECO:0000269|PubMed:9488694}. Extracellular vesicle {ECO:0000269|PubMed:26387950}. Endosome, multivesicular body {ECO:0000269|PubMed:26387950}. Note=In the plasma, APOE is associated with chylomicrons, chylomicrons remnants, VLDL, LDL and HDL lipoproteins (PubMed:1911868, PubMed:8340399). Lipid poor oligomeric APOE is associated with the extracellular matrix in a calcium- and heparan-sulfate proteoglycans-dependent manner (PubMed:9488694). Lipidation induces the release from the extracellular matrix (PubMed:9488694). Colocalizes with CD63 and PMEL at exosomes and in intraluminal vesicles within multivesicular endosomes. {ECO:0000269|PubMed:1911868, ECO:0000269|PubMed:26387950, ECO:0000269|PubMed:8340399, ECO:0000269|PubMed:9488694}.
uniprot
proteins