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Protein

Apolipoprotein E

Gene

APOE

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

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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:6860692, PubMed:1911868, PubMed:14754908). APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance (PubMed:6860692, PubMed:2762297, PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:14754908, PubMed:23620513). Apoliproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma (PubMed:6860692, PubMed:2762297, 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:6860692, PubMed:1911868). 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:2762297, PubMed:1917954, PubMed:7768901, PubMed:8939961, PubMed:12950167, PubMed:20030366, PubMed:2063194, PubMed:8756331, PubMed:20303980, PubMed:1530612, PubMed:7635945). Finally, APOE has also 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:9395455, PubMed:9488694, PubMed:23676495, PubMed:7635945). 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:9395455, PubMed:23676495, PubMed:29516132). 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 to the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis (PubMed:2762297, PubMed:1917954, 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:9395455, PubMed:14754908, PubMed:23620513). 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:8939961, PubMed:25173806). APOE in also involved in innate and adaptive immune responses, controlling for instance the survival of myeloid-derived suppressor cells (By similarity). 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).2 PublicationsBy similarity19 Publications

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

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

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-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

SIGNOR Signaling Network Open Resource

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SIGNORi
P02649

Protein family/group databases

MoonDB Database of extreme multifunctional and moonlighting proteins

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MoonDBi
P02649 Predicted

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Apolipoprotein E
Short name:
Apo-E
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:APOE
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 19

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000130203.9

Human Gene Nomenclature Database

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HGNCi
HGNC:613 APOE

Online Mendelian Inheritance in Man (OMIM)

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MIMi
107741 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P02649

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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, Extracellular matrix, HDL, Secreted, VLDL

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Hyperlipoproteinemia 3 (HLPP3)8 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
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_00064631E → K in HLPP3; ApoE4 Philadelphia, ApoE5 French-Canadian and ApoE5-type; only ApoE4 Philadelphia is associated with HLPP3. 1 Publication2 PublicationsCorresponds to variant dbSNP:rs201672011EnsemblClinVar.1
Natural variantiVAR_000652130C → R in HLPP3 and AD2; ApoE4, ApoE3 Leiden, ApoE3**, ApoE5-Frankfurt and ApoE5-type; ApoE3 Leiden and ApoE3** are associated with HLPP3; ApoE4 is associated with AD2; changed protein structure; no effect on binding to LDL receptor; decreased association with HDL and enrichment in VLDL and IDL; may prevent the interaction with MAP2 and MAPT; changed interaction with APP/A4 amyloid-beta peptide; increased ability to induce APP transcription; increased C-terminal proteolytic processing in neurons; decreased function in neurite outgrowth. 1 Publication17 PublicationsCorresponds to variant dbSNP:rs429358EnsemblClinVar.1
Natural variantiVAR_000654145G → GEVQAMLG in HLPP3; ApoE3 Leiden; no effect on glycosylation. 2 Publications1
Natural variantiVAR_000657154R → C in HLPP3; ApoE2-type. 1 PublicationCorresponds to variant dbSNP:rs121918393EnsemblClinVar.1
Natural variantiVAR_000656154R → S in HLPP3; ApoE2 Christchurch; decreased binding to LDL receptor. 3 PublicationsCorresponds to variant dbSNP:rs121918393EnsemblClinVar.1
Natural variantiVAR_000658160R → C in HLPP3; ApoE3**. 1 PublicationCorresponds to variant dbSNP:rs387906567EnsemblClinVar.1
Natural variantiVAR_000659163R → C in HLPP3 and FH; ApoE4 Philadelphia and ApoE2-type. 3 PublicationsCorresponds to variant dbSNP:rs769455EnsemblClinVar.1
Natural variantiVAR_000660163R → H in HLPP3; unknown pathological significance; ApoE Kochi. 1 PublicationCorresponds to variant dbSNP:rs121918397EnsemblClinVar.1
Natural variantiVAR_000662164K → E in HLPP3; ApoE1 Harrisburg; decreased binding to LDL receptor; probable dominant negative effect; decreased in vitro binding to heparin. 1 PublicationCorresponds to variant dbSNP:rs121918394EnsemblClinVar.1
Natural variantiVAR_000661164K → Q in HLPP3; ApoE2**. Corresponds to variant dbSNP:rs121918394EnsemblClinVar.1
Natural variantiVAR_000664176R → C in HLPP3; ApoE2, ApoE2 Fukuoka, ApoE1 Weisgraber and ApoE3**; ApoE3** is associated with HLPP3; changed protein structure; decreased binding to LDLR and other lipoprotein receptors; decreased in vitro binding to heparin; no effect on distribution among plasma lipoproteins. 9 PublicationsCorresponds to variant dbSNP:rs7412EnsemblClinVar.1
Natural variantiVAR_081136228 – 317Missing in HLPP3; ApoE3 Washington. 1 PublicationAdd BLAST90
Natural variantiVAR_000668262 – 263EE → KK in HLPP3; ApoE7 Suita. 1 Publication2
Alzheimer disease 2 (AD2)11 Publications
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
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_000652130C → R in HLPP3 and AD2; ApoE4, ApoE3 Leiden, ApoE3**, ApoE5-Frankfurt and ApoE5-type; ApoE3 Leiden and ApoE3** are associated with HLPP3; ApoE4 is associated with AD2; changed protein structure; no effect on binding to LDL receptor; decreased association with HDL and enrichment in VLDL and IDL; may prevent the interaction with MAP2 and MAPT; changed interaction with APP/A4 amyloid-beta peptide; increased ability to induce APP transcription; increased C-terminal proteolytic processing in neurons; decreased function in neurite outgrowth. 1 Publication17 PublicationsCorresponds to variant dbSNP:rs429358EnsemblClinVar.1
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
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035015167Missing in SBHD and FH; also found in patients with a diagnosis of familial combined hyperlipidemia. 6 Publications1
Lipoprotein glomerulopathy (LPG)4 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; ApoE2 Kyoto. 2 PublicationsCorresponds to variant dbSNP:rs121918399EnsemblClinVar.1
Natural variantiVAR_042735163R → P in LPG; ApoE2 Sendai; decreased binding to LDL receptor; induces intraglomerular deposition of ApoE-containing lipoproteins. 2 PublicationsCorresponds 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; ApoE4 Freiburg. 2 PublicationsCorresponds to variant dbSNP:rs769452EnsemblClinVar.1
Natural variantiVAR_000653145G → D in FH; unknown pathological significance; ApoE1 Weisgraber. 2 PublicationsCorresponds to variant dbSNP:rs267606664EnsemblClinVar.1
Natural variantiVAR_000659163R → C in HLPP3 and FH; ApoE4 Philadelphia and ApoE2-type. 3 PublicationsCorresponds to variant dbSNP:rs769455EnsemblClinVar.1
Natural variantiVAR_035015167Missing in SBHD and FH; also found in patients with a diagnosis of familial combined hyperlipidemia. 6 Publications1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi79R → T: Changes the plasma lipoprotein distribution of ApoE4 to the HDL. 1 Publication1
Mutagenesisi127E → A: No effect on plasma lipoprotein distribution. 1 Publication1
Mutagenesisi157S → R: Increased binding to LDL receptor; when associated with A-167. 1 Publication1
Mutagenesisi158H → A: Decreased binding to LDL receptor. 1 Publication1
Mutagenesisi161K → A: Decreased binding to LDL receptor. 1 Publication1
Mutagenesisi162L → P: Decreased binding to LDL receptor. 1 Publication1
Mutagenesisi167L → A: Increased binding to LDL receptor; when associated with R-157. 1 Publication1
Mutagenesisi168R → A: Decreased binding to LDL receptor. 1 Publication1
Mutagenesisi172D → A: Restores the LDL receptor binding activity of ApoE2. 1 Publication1
Mutagenesisi212T → A: Loss of O-glycosylation. 1 Publication1

Keywords - Diseasei

Alzheimer disease, Amyloidosis, Disease mutation, Hyperlipidemia, Neurodegeneration

Organism-specific databases

DisGeNET

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DisGeNETi
348

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
APOE

MalaCards human disease database

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MalaCardsi
APOE
MIMi104310 phenotype
143890 phenotype
269600 phenotype
611771 phenotype
617347 phenotype

Open Targets

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OpenTargetsi
ENSG00000130203

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
412 Hyperlipoproteinemia type 3
329481 Lipoprotein glomerulopathy
238616 NON RARE IN EUROPE: Alzheimer disease
1648 NON RARE IN EUROPE: Dementia with Lewy body
406 NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia
158029 Sea-blue histiocytosis

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA55

Chemistry databases

Drug and drug target database

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DrugBanki
DB00062 Human Serum Albumin
DB00064 Serum albumin iodonated

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
APOE

Domain mapping of disease mutations (DMDM)

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DMDMi
114039

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 181 PublicationAdd BLAST18
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000000198719 – 317Apolipoprotein EAdd BLAST299

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi26O-linked (GalNAc...) threonine1 Publication1
Glycosylationi36O-linked (GalNAc...) threonine1 Publication1
Glycosylationi93N-linked (Glc) (glycation) lysine1 Publication1
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei143Methionine sulfoxideBy similarity1
Modified residuei147Phosphoserine; by FAM20CCombined sources1 Publication1
Glycosylationi212O-linked (GalNAc...) threonine2 Publications1
Glycosylationi307O-linked (GalNAc...) threonine1 Publication1
Glycosylationi308O-linked (GalNAc...) serine2 Publications1
Glycosylationi314O-linked (GalNAc...) serine1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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:2498325, PubMed:19838169, PubMed:20511397, PubMed:23234360). 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).1 Publication4 Publications
Glycated in plasma VLDL of normal subjects, and of hyperglycemic diabetic patients at a higher level (2-3 fold).1 Publication
Phosphorylated by FAM20C in the extracellular medium.1 Publication
Undergoes C-terminal proteolytic processing in neurons. C-terminally truncated APOE has a tendency to form neurotoxic intracellular neurofibrillary tangle-like inclusions in neurons.1 Publication

Keywords - PTMi

Glycation, Glycoprotein, Oxidation, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P02649

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P02649

MaxQB - The MaxQuant DataBase

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MaxQBi
P02649

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P02649

PeptideAtlas

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PeptideAtlasi
P02649

PRoteomics IDEntifications database

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PRIDEi
P02649

ProteomicsDB human proteome resource

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ProteomicsDBi
51537

2D gel databases

DOSAC-COBS 2D-PAGE database

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DOSAC-COBS-2DPAGEi
P02649

Two-dimensional polyacrylamide gel electrophoresis database from the Geneva University Hospital

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SWISS-2DPAGEi
P02649

PTM databases

CarbonylDB database of protein carbonylation sites

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CarbonylDBi
P02649

GlyConnect protein glycosylation platform

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GlyConnecti
648

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P02649

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P02649

SwissPalm database of S-palmitoylation events

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SwissPalmi
P02649

UniCarbKB; an annotated and curated database of glycan structures

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UniCarbKBi
P02649

Miscellaneous databases

CutDB - Proteolytic event database

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PMAP-CutDBi
P02649

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Produced by several tissues and cell types and mainly found associated with lipid particles in the plasma, the interstitial fluid and lymph (PubMed:25173806). Mainly synthesized by liver hepatocytes (PubMed:25173806). Significant quantities are also produced in brain, mainly by astrocytes and glial cells in the cerebral cortex, but also by neurons in frontal cortex and hippocampus (PubMed:3115992, PubMed:10027417). It is also expressed by cells of the peripheral nervous system (PubMed:10027417, PubMed:25173806). Also expressed by adrenal gland, testis, ovary, skin, kidney, spleen and adipose tissue and macrophages in various tissues (PubMed:25173806).1 Publication2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000130203 Expressed in 224 organ(s), highest expression level in left adrenal gland

CleanEx database of gene expression profiles

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CleanExi
HS_APOE

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P02649 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P02649 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB008363
CAB069921
HPA065539
HPA068768

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homotetramer (PubMed:8340399). May interact with ABCA1; functionally associated with ABCA1 in the biogenesis of HDLs (PubMed:14754908). May interact with APP/A4 amyloid-beta peptide; the interaction is extremely stable in vitro but its physiological significance is unclear (PubMed:8367470, PubMed:23620513). May interact with MAPT (PubMed:7972031). May interact with MAP2 (PubMed:7891887).6 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
106845, 77 interactors

Database of interacting proteins

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DIPi
DIP-1120N

Protein interaction database and analysis system

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IntActi
P02649, 34 interactors

Molecular INTeraction database

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MINTi
P02649

STRING: functional protein association networks

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STRINGi
9606.ENSP00000252486

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1317
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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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[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
P02649

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P02649

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P02649

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>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
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni80 – 2558 X 22 AA approximate tandem repeatsAdd BLAST176
Regioni158 – 168LDL and other lipoprotein receptors binding2 PublicationsAdd BLAST11
Regioni162 – 165Heparin-binding1 Publication4
Regioni210 – 290Lipid-binding and lipoprotein association2 PublicationsAdd BLAST81
Regioni229 – 236Heparin-binding1 Publication8
Regioni266 – 317Homooligomerization1 PublicationAdd BLAST52
Regioni278 – 290Specificity for association with VLDL1 PublicationAdd BLAST13

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the apolipoprotein A1/A4/E family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
ENOG410IVK0 Eukaryota
ENOG4111MYC LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00730000111315

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
HOG000034006

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG010582

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
P02649

KEGG Orthology (KO)

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KOi
K04524

Identification of Orthologs from Complete Genome Data

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OMAi
ARLKGWF

Database of Orthologous Groups

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OrthoDBi
1344247at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P02649

TreeFam database of animal gene trees

More...
TreeFami
TF334458

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR000074 ApoA_E

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF01442 Apolipoprotein, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i91AFC04210A30689
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PEV4E9PEV4_HUMAN
Apolipoprotein E
APOE
216Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
E7ERP7E7ERP7_HUMAN
Apolipoprotein E
APOE
219Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0Y7L5H0Y7L5_HUMAN
Apolipoprotein E
APOE
269Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

There are three common APOE alleles identified: APOE*2/APOE-epsilon2/E2, APOE*3/APOE-epsilon3/E3, and APOE*4/APOE-epsilon4/E4. The corresponding ApoE2, ApoE3 and ApoE4 isoforms differentially present Cys and Arg residues at positions 130 and 176. The most common allele in the human population is APOE*3 which sequence is the one displayed in that entry with a Cys at position 130 and an Arg at position 176. Common APOE variants influence lipoprotein metabolism in healthy individuals. Additional variants have been described and are described relative to the three common alleles.1 Publication3 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00064521E → K in ApoE5; associated with hyperlipoproteinemia and atherosclerosis; increased binding to LDL receptor. 2 PublicationsCorresponds to variant dbSNP:rs121918392EnsemblClinVar.1
Natural variantiVAR_00064631E → K in HLPP3; ApoE4 Philadelphia, ApoE5 French-Canadian and ApoE5-type; only ApoE4 Philadelphia is associated with HLPP3. 1 Publication2 PublicationsCorresponds to variant dbSNP:rs201672011EnsemblClinVar.1
Natural variantiVAR_04273443R → C in LPG; ApoE2 Kyoto. 2 PublicationsCorresponds to variant dbSNP:rs121918399EnsemblClinVar.1
Natural variantiVAR_00064746L → P in FH; unknown pathological significance; ApoE4 Freiburg. 2 PublicationsCorresponds to variant dbSNP:rs769452EnsemblClinVar.1
Natural variantiVAR_00064860T → A in ApoE3 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 ApoE5 Frankfurt. 1 PublicationCorresponds to variant dbSNP:rs1180612218Ensembl.1
Natural variantiVAR_000650102P → R in ApoE5-type; no hyperlipidemia. 1 PublicationCorresponds to variant dbSNP:rs11083750EnsemblClinVar.1
Natural variantiVAR_000651117A → T in ApoE3*. 1 PublicationCorresponds to variant dbSNP:rs28931577EnsemblClinVar.1
Natural variantiVAR_016789124A → V in ApoE3 Basel. 1 PublicationCorresponds to variant dbSNP:rs937063425Ensembl.1
Natural variantiVAR_000652130C → R in HLPP3 and AD2; ApoE4, ApoE3 Leiden, ApoE3**, ApoE5-Frankfurt and ApoE5-type; ApoE3 Leiden and ApoE3** are associated with HLPP3; ApoE4 is associated with AD2; changed protein structure; no effect on binding to LDL receptor; decreased association with HDL and enrichment in VLDL and IDL; may prevent the interaction with MAP2 and MAPT; changed interaction with APP/A4 amyloid-beta peptide; increased ability to induce APP transcription; increased C-terminal proteolytic processing in neurons; decreased function in neurite outgrowth. 1 Publication17 PublicationsCorresponds to variant dbSNP:rs429358EnsemblClinVar.1
Natural variantiVAR_000653145G → D in FH; unknown pathological significance; ApoE1 Weisgraber. 2 PublicationsCorresponds to variant dbSNP:rs267606664EnsemblClinVar.1
Natural variantiVAR_000654145G → GEVQAMLG in HLPP3; ApoE3 Leiden; no effect on glycosylation. 2 Publications1
Natural variantiVAR_000655152R → Q in ApoE2-type; no hyperlipidemia. 1 PublicationCorresponds to variant dbSNP:rs28931578EnsemblClinVar.1
Natural variantiVAR_000657154R → C in HLPP3; ApoE2-type. 1 PublicationCorresponds to variant dbSNP:rs121918393EnsemblClinVar.1
Natural variantiVAR_000656154R → S in HLPP3; ApoE2 Christchurch; decreased binding to LDL receptor. 3 PublicationsCorresponds to variant dbSNP:rs121918393EnsemblClinVar.1
Natural variantiVAR_000658160R → C in HLPP3; ApoE3**. 1 PublicationCorresponds to variant dbSNP:rs387906567EnsemblClinVar.1
Natural variantiVAR_000659163R → C in HLPP3 and FH; ApoE4 Philadelphia and ApoE2-type. 3 PublicationsCorresponds to variant dbSNP:rs769455EnsemblClinVar.1
Natural variantiVAR_000660163R → H in HLPP3; unknown pathological significance; ApoE Kochi. 1 PublicationCorresponds to variant dbSNP:rs121918397EnsemblClinVar.1
Natural variantiVAR_042735163R → P in LPG; ApoE2 Sendai; decreased binding to LDL receptor; induces intraglomerular deposition of ApoE-containing lipoproteins. 2 PublicationsCorresponds to variant dbSNP:rs121918397EnsemblClinVar.1
Natural variantiVAR_000662164K → E in HLPP3; ApoE1 Harrisburg; decreased binding to LDL receptor; probable dominant negative effect; decreased in vitro binding to heparin. 1 PublicationCorresponds to variant dbSNP:rs121918394EnsemblClinVar.1
Natural variantiVAR_000661164K → Q in HLPP3; ApoE2**. 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 ApoE3*; decreased binding to LDL receptor. 2 PublicationsCorresponds to variant dbSNP:rs267606662EnsemblClinVar.1
Natural variantiVAR_000664176R → C in HLPP3; ApoE2, ApoE2 Fukuoka, ApoE1 Weisgraber and ApoE3**; ApoE3** is associated with HLPP3; changed protein structure; decreased binding to LDLR and other lipoprotein receptors; decreased in vitro binding to heparin; no effect on distribution among plasma lipoproteins. 9 PublicationsCorresponds to variant dbSNP:rs7412EnsemblClinVar.1
Natural variantiVAR_081136228 – 317Missing in HLPP3; ApoE3 Washington. 1 PublicationAdd BLAST90
Natural variantiVAR_000665242R → Q in ApoE2 Fukuoka. 1 PublicationCorresponds to variant dbSNP:rs267606663EnsemblClinVar.1
Natural variantiVAR_000666246R → C in ApoE2 Dunedin. 1 PublicationCorresponds to variant dbSNP:rs121918395EnsemblClinVar.1
Natural variantiVAR_000667254V → E in ApoE2 WG. 1 PublicationCorresponds to variant dbSNP:rs199768005EnsemblClinVar.1
Natural variantiVAR_000668262 – 263EE → KK in HLPP3; ApoE7 Suita. 1 Publication2
Natural variantiVAR_000669269R → G in ApoE3 HB. 2 PublicationsCorresponds to variant dbSNP:rs267606661EnsemblClinVar.1
Natural variantiVAR_000670270L → E in ApoE1 HE; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_000671292R → H in ApoE4 PD. 1 PublicationCorresponds to variant dbSNP:rs121918398EnsemblClinVar.1
Natural variantiVAR_000672314S → R in ApoE4 HG. 1 PublicationCorresponds to variant dbSNP:rs28931579EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
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

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS12647.1

Protein sequence database of the Protein Information Resource

More...
PIRi
A92478 LPHUE

NCBI Reference Sequences

More...
RefSeqi
NP_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

UniGene gene-oriented nucleotide sequence clusters

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UniGenei
Hs.654439

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000252486; ENSP00000252486; ENSG00000130203

Database of genes from NCBI RefSeq genomes

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GeneIDi
348

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:348

UCSC genome browser

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UCSCi
uc002pab.4 human

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

Apolipoprotein E entry

Protein Spotlight

Tangled - Issue 83 of June 2007

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

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...

Protein-protein interaction databases

BioGridi106845, 77 interactors
DIPiDIP-1120N
IntActiP02649, 34 interactors
MINTiP02649
STRINGi9606.ENSP00000252486

Chemistry databases

DrugBankiDB00062 Human Serum Albumin
DB00064 Serum albumin iodonated

Protein family/group databases

MoonDBiP02649 Predicted

PTM databases

CarbonylDBiP02649
GlyConnecti648
iPTMnetiP02649
PhosphoSitePlusiP02649
SwissPalmiP02649
UniCarbKBiP02649

Polymorphism and mutation databases

BioMutaiAPOE
DMDMi114039

2D gel databases

DOSAC-COBS-2DPAGEiP02649
SWISS-2DPAGEiP02649

Proteomic databases

EPDiP02649
jPOSTiP02649
MaxQBiP02649
PaxDbiP02649
PeptideAtlasiP02649
PRIDEiP02649
ProteomicsDBi51537

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
348
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000252486; ENSP00000252486; ENSG00000130203
GeneIDi348
KEGGihsa:348
UCSCiuc002pab.4 human

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
348
DisGeNETi348
EuPathDBiHostDB:ENSG00000130203.9

GeneCards: human genes, protein and diseases

More...
GeneCardsi
APOE
GeneReviewsiAPOE
HGNCiHGNC:613 APOE
HPAiCAB008363
CAB069921
HPA065539
HPA068768
MalaCardsiAPOE
MIMi104310 phenotype
107741 gene
143890 phenotype
269600 phenotype
611771 phenotype
617347 phenotype
neXtProtiNX_P02649
OpenTargetsiENSG00000130203
Orphaneti412 Hyperlipoproteinemia type 3
329481 Lipoprotein glomerulopathy
238616 NON RARE IN EUROPE: Alzheimer disease
1648 NON RARE IN EUROPE: Dementia with Lewy body
406 NON RARE IN EUROPE: Heterozygous familial hypercholesterolemia
158029 Sea-blue histiocytosis
PharmGKBiPA55

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiENOG410IVK0 Eukaryota
ENOG4111MYC LUCA
GeneTreeiENSGT00730000111315
HOGENOMiHOG000034006
HOVERGENiHBG010582
InParanoidiP02649
KOiK04524
OMAiARLKGWF
OrthoDBi1344247at2759
PhylomeDBiP02649
TreeFamiTF334458

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

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
APOE human
EvolutionaryTraceiP02649

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
Apolipoprotein_E

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
348
PMAP-CutDBiP02649

Protein Ontology

More...
PROi
PR:P02649

The Stanford Online Universal Resource for Clones and ESTs

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Gene expression databases

BgeeiENSG00000130203 Expressed in 224 organ(s), highest expression level in left adrenal gland
CleanExiHS_APOE
ExpressionAtlasiP02649 baseline and differential
GenevisibleiP02649 HS

Family and domain databases

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

ProtoNet; Automatic hierarchical classification of proteins

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<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiAPOE_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P02649
Secondary accession number(s): B2RC15, C0JYY5, Q9P2S4
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: January 16, 2019
This is version 238 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  7. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
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