APOE: Polycystic Ovarian Syndrome Database

Gene Information

Gene Symbol

APOE

Aliases

AD2, APO-E, ApoE4, LDLCQ5, LPG

Entrez Gene ID

348

Gene Name

Apolipoprotein E

Chromosomal Location

19q13.32

HGNC ID

HGNC:613

Summary

The protein encoded by this gene is a major apoprotein of the chylomicron. It binds to a specific liver and peripheral cell receptor, and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes. Mutations in this gene result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants. [provided by RefSeq, Jun 2016]

RefSeq DNA

NG_007084.2

RefSeq mRNA

NM_000041.4, NM_001302688.2, NM_001302689.2, NM_001302690.1, NM_001302691.2

e!Ensembl

Gene	ENSG00000130203
Transcript	ENST00000252486, ENST00000446996, ENST00000434152, ENST00000425718
Protein	ENSP00000252486, ENSP00000413135, ENSP00000413653, ENSP00000410423

Gene Ontology (GO)

Show/Hide all(168 )

GO ID	Ontology	Function	Evidence	Reference
GO:0000302	Biological process	Response to reactive oxygen species	NAS	11743999
GO:0001937	Biological process	Negative regulation of endothelial cell proliferation	IDA	9685360
GO:0006641	Biological process	Triglyceride metabolic process	IDA	9649566
GO:0006641	Biological process	Triglyceride metabolic process	IMP	3771793
GO:0006695	Biological process	Cholesterol biosynthetic process	IBA	21873635
GO:0006707	Biological process	Cholesterol catabolic process	IBA	21873635
GO:0006898	Biological process	Receptor-mediated endocytosis	IDA	1917954
GO:0006898	Biological process	Receptor-mediated endocytosis	TAS	22138302
GO:0007010	Biological process	Cytoskeleton organization	TAS	9622609
GO:0007186	Biological process	G protein-coupled receptor signaling pathway	IDA	16443932
GO:0007263	Biological process	Nitric oxide mediated signal transduction	IDA	8995232
GO:0007271	Biological process	Synaptic transmission, cholinergic	TAS	9622609
GO:0007616	Biological process	Long-term memory	IGI	24412220
GO:0008203	Biological process	Cholesterol metabolic process	IDA	9649566
GO:0008203	Biological process	Cholesterol metabolic process	IMP	3771793
GO:0010544	Biological process	Negative regulation of platelet activation	IDA	8995232
GO:0010596	Biological process	Negative regulation of endothelial cell migration	IMP	23142051
GO:0010873	Biological process	Positive regulation of cholesterol esterification	IBA	21873635
GO:0010873	Biological process	Positive regulation of cholesterol esterification	IDA	15654758
GO:0010875	Biological process	Positive regulation of cholesterol efflux	IDA	12042316, 14754908
GO:0010875	Biological process	Positive regulation of cholesterol efflux	IGI	12401887
GO:0010976	Biological process	Positive regulation of neuron projection development	IDA	7592957, 23845000
GO:0010977	Biological process	Negative regulation of neuron projection development	IDA	7592957
GO:0015909	Biological process	Long-chain fatty acid transport	IDA	24345162
GO:0017038	Biological process	Protein import	IDA	24446231
GO:0019068	Biological process	Virion assembly	IMP	25122793
GO:0019433	Biological process	Triglyceride catabolic process	IBA	21873635
GO:0019934	Biological process	CGMP-mediated signaling	IDA	8995232
GO:0030195	Biological process	Negative regulation of blood coagulation	IDA	8995232
GO:0030516	Biological process	Regulation of axon extension	TAS	9622609
GO:0031175	Biological process	Neuron projection development	IDA	8939961
GO:0032269	Biological process	Negative regulation of cellular protein metabolic process	IGI	16805831
GO:0032374	Biological process	Regulation of cholesterol transport	IBA	21873635
GO:0032462	Biological process	Regulation of protein homooligomerization	IDA	25207746
GO:0032489	Biological process	Regulation of Cdc42 protein signal transduction	IDA	16443932
GO:0032805	Biological process	Positive regulation of low-density lipoprotein particle receptor catabolic process	IDA	15950758
GO:0033344	Biological process	Cholesterol efflux	IBA	21873635
GO:0033344	Biological process	Cholesterol efflux	IDA	11162594, 16443932, 23620513
GO:0033700	Biological process	Phospholipid efflux	IBA	21873635
GO:0033700	Biological process	Phospholipid efflux	IDA	11162594
GO:0034372	Biological process	Very-low-density lipoprotein particle remodeling	IBA	21873635
GO:0034372	Biological process	Very-low-density lipoprotein particle remodeling	IDA	15654758
GO:0034372	Biological process	Very-low-density lipoprotein particle remodeling	IGI	12401887
GO:0034375	Biological process	High-density lipoprotein particle remodeling	IGI	12401887
GO:0034380	Biological process	High-density lipoprotein particle assembly	IBA	21873635
GO:0034380	Biological process	High-density lipoprotein particle assembly	IDA	14754908, 17305370
GO:0034382	Biological process	Chylomicron remnant clearance	IDA	1911868
GO:0034382	Biological process	Chylomicron remnant clearance	IMP	7175379
GO:0034384	Biological process	High-density lipoprotein particle clearance	IDA	210175
GO:0034447	Biological process	Very-low-density lipoprotein particle clearance	IDA	1917954, 2762297
GO:0034447	Biological process	Very-low-density lipoprotein particle clearance	IMP	9649566
GO:0035641	Biological process	Locomotory exploration behavior	IMP	24412220
GO:0042157	Biological process	Lipoprotein metabolic process	IBA	21873635
GO:0042158	Biological process	Lipoprotein biosynthetic process	IDA	23620513
GO:0042159	Biological process	Lipoprotein catabolic process	IBA	21873635
GO:0042632	Biological process	Cholesterol homeostasis	IBA	21873635
GO:0042632	Biological process	Cholesterol homeostasis	IDA	9649566
GO:0042632	Biological process	Cholesterol homeostasis	IGI	24412220
GO:0042982	Biological process	Amyloid precursor protein metabolic process	IDA	21593558
GO:0043407	Biological process	Negative regulation of MAP kinase activity	IDA	9685360
GO:0043524	Biological process	Negative regulation of neuron apoptotic process	IBA	21873635
GO:0043537	Biological process	Negative regulation of blood vessel endothelial cell migration	IDA	9685360
GO:0043691	Biological process	Reverse cholesterol transport	IBA	21873635
GO:0043691	Biological process	Reverse cholesterol transport	IDA	8127890
GO:0044794	Biological process	Positive regulation by host of viral process	IMP	25122793
GO:0045541	Biological process	Negative regulation of cholesterol biosynthetic process	IDA	1917954
GO:0045807	Biological process	Positive regulation of endocytosis	IDA	7683668, 8300609
GO:0045893	Biological process	Positive regulation of transcription, DNA-templated	IMP	28111074
GO:0046889	Biological process	Positive regulation of lipid biosynthetic process	IBA	21873635
GO:0046889	Biological process	Positive regulation of lipid biosynthetic process	IDA	12042316
GO:0046907	Biological process	Intracellular transport	TAS	9622609
GO:0048168	Biological process	Regulation of neuronal synaptic plasticity	TAS	9622609
GO:0050709	Biological process	Negative regulation of protein secretion	IMP	27044754
GO:0050728	Biological process	Negative regulation of inflammatory response	IC	8995232
GO:0051000	Biological process	Positive regulation of nitric-oxide synthase activity	IBA	21873635
GO:0051000	Biological process	Positive regulation of nitric-oxide synthase activity	IDA	8995232
GO:0051044	Biological process	Positive regulation of membrane protein ectodomain proteolysis	IDA	15950758
GO:0051044	Biological process	Positive regulation of membrane protein ectodomain proteolysis	IGI	25015123
GO:0051246	Biological process	Regulation of protein metabolic process	IGI	24412220
GO:0055089	Biological process	Fatty acid homeostasis	IDA	24345162
GO:0060999	Biological process	Positive regulation of dendritic spine development	IDA	24328732
GO:0061136	Biological process	Regulation of proteasomal protein catabolic process	IMP	28111074
GO:0061771	Biological process	Response to caloric restriction	IGI	24412220
GO:0070374	Biological process	Positive regulation of ERK1 and ERK2 cascade	IMP	28111074
GO:0071830	Biological process	Triglyceride-rich lipoprotein particle clearance	IMP	23676495
GO:0071831	Biological process	Intermediate-density lipoprotein particle clearance	IDA	1917954
GO:0090090	Biological process	Negative regulation of canonical Wnt signaling pathway	IDA	16805831
GO:0090090	Biological process	Negative regulation of canonical Wnt signaling pathway	IGI	16805831
GO:0090090	Biological process	Negative regulation of canonical Wnt signaling pathway	TAS	22988876
GO:0090181	Biological process	Regulation of cholesterol metabolic process	IGI	24412220
GO:0097113	Biological process	AMPA glutamate receptor clustering	IDA	24328732
GO:0097114	Biological process	NMDA glutamate receptor clustering	IDA	24328732
GO:1900221	Biological process	Regulation of amyloid-beta clearance	IBA	21873635
GO:1900221	Biological process	Regulation of amyloid-beta clearance	IDA	24446231
GO:1900272	Biological process	Negative regulation of long-term synaptic potentiation	IDA	16273551
GO:1901215	Biological process	Negative regulation of neuron death	IDA	24259049
GO:1901628	Biological process	Positive regulation of postsynaptic membrane organization	IDA	24259049
GO:1901630	Biological process	Negative regulation of presynaptic membrane organization	IDA	24259049
GO:1902430	Biological process	Negative regulation of amyloid-beta formation	IDA	24154541
GO:1902952	Biological process	Positive regulation of dendritic spine maintenance	IDA	24328732
GO:1902995	Biological process	Positive regulation of phospholipid efflux	IDA	12042316
GO:1903002	Biological process	Positive regulation of lipid transport across blood brain barrier	IDA	24345162
GO:1905855	Biological process	Positive regulation of heparan sulfate binding	IDA	7683668
GO:1905860	Biological process	Positive regulation of heparan sulfate proteoglycan binding	IDA	8300609
GO:1905890	Biological process	Regulation of cellular response to very-low-density lipoprotein particle stimulus	IDA	7592957
GO:1905906	Biological process	Regulation of amyloid fibril formation	IDA	25207746
GO:1905908	Biological process	Positive regulation of amyloid fibril formation	TAS	9228033, 20005821
GO:2000822	Biological process	Regulation of behavioral fear response	IMP	24412220
GO:0005576	Cellular component	Extracellular region	HDA	27068509
GO:0005576	Cellular component	Extracellular region	IDA	8089103, 16805831
GO:0005615	Cellular component	Extracellular space	HDA	16502470, 20551380
GO:0005615	Cellular component	Extracellular space	IDA	8340399
GO:0005634	Cellular component	Nucleus	HDA	21630459
GO:0005737	Cellular component	Cytoplasm	NAS	8083695
GO:0005737	Cellular component	Cytoplasm	TAS	9622609
GO:0005783	Cellular component	Endoplasmic reticulum	IDA	25122793
GO:0005794	Cellular component	Golgi apparatus	IDA	25122793
GO:0016020	Cellular component	Membrane	HDA	19946888
GO:0030425	Cellular component	Dendrite	NAS	8083695
GO:0031012	Cellular component	Extracellular matrix	IDA	9488694
GO:0034361	Cellular component	Very-low-density lipoprotein particle	IDA	2280190, 8071364, 8245722, 9211985, 17154273, 22138302
GO:0034362	Cellular component	Low-density lipoprotein particle	IDA	2280190, 8245722, 9211985, 22138302
GO:0034363	Cellular component	Intermediate-density lipoprotein particle	IBA	21873635
GO:0034363	Cellular component	Intermediate-density lipoprotein particle	IDA	2280190, 9211985, 17336988, 22138302
GO:0034364	Cellular component	High-density lipoprotein particle	IBA	21873635
GO:0034364	Cellular component	High-density lipoprotein particle	IDA	210174, 2280190, 8071364, 9211985, 14754908, 22138302
GO:0034365	Cellular component	Discoidal high-density lipoprotein particle	TAS	22383525
GO:0042627	Cellular component	Chylomicron	IBA	21873635
GO:0042627	Cellular component	Chylomicron	IDA	8245722, 16935699
GO:0043025	Cellular component	Neuronal cell body	NAS	8083695
GO:0043083	Cellular component	Synaptic cleft	IDA	22637583
GO:0062023	Cellular component	Collagen-containing extracellular matrix	HDA	23658023, 27559042
GO:0070062	Cellular component	Extracellular exosome	HDA	19056867, 20458337, 23533145
GO:0072562	Cellular component	Blood microparticle	HDA	22516433
GO:0098978	Cellular component	Glutamatergic synapse	IDA	22637583
GO:1903561	Cellular component	Extracellular vesicle	HDA	24769233
GO:1990777	Cellular component	Lipoprotein particle	IDA	22138302
GO:0001540	Molecular function	Amyloid-beta binding	IBA	21873635
GO:0001540	Molecular function	Amyloid-beta binding	IDA	8089103, 11305869, 25207746
GO:0001540	Molecular function	Amyloid-beta binding	IPI	9003062, 9211985, 22138302
GO:0005102	Molecular function	Signaling receptor binding	IPI	27477018
GO:0005198	Molecular function	Structural molecule activity	TAS	22138302
GO:0005319	Molecular function	Lipid transporter activity	IDA	17305370
GO:0005515	Molecular function	Protein binding	IPI	7972031, 8245722, 12950167, 14754908, 15615705, 17116874, 19758344, 21163940, 21593558, 24447298, 25122793
GO:0005543	Molecular function	Phospholipid binding	IBA	21873635
GO:0005543	Molecular function	Phospholipid binding	IDA	4066713
GO:0008201	Molecular function	Heparin binding	IDA	2745454, 7635945
GO:0008289	Molecular function	Lipid binding	IDA	4066713
GO:0015485	Molecular function	Cholesterol binding	IBA	21873635
GO:0016209	Molecular function	Antioxidant activity	IDA	9685360
GO:0042802	Molecular function	Identical protein binding	IDA	4066713, 8340399
GO:0042803	Molecular function	Protein homodimerization activity	IDA	8089103, 9211985
GO:0042803	Molecular function	Protein homodimerization activity	IPI	8245722
GO:0043395	Molecular function	Heparan sulfate proteoglycan binding	IDA	9488694, 23676495
GO:0044877	Molecular function	Protein-containing complex binding	IDA	25207746
GO:0046911	Molecular function	Metal chelating activity	IDA	9685360
GO:0046983	Molecular function	Protein dimerization activity	IDA	22138302
GO:0048156	Molecular function	Tau protein binding	IPI	7566652
GO:0050750	Molecular function	Low-density lipoprotein particle receptor binding	IBA	21873635
GO:0050750	Molecular function	Low-density lipoprotein particle receptor binding	IDA	210175, 1530612, 7635945
GO:0050750	Molecular function	Low-density lipoprotein particle receptor binding	IPI	17326667
GO:0050750	Molecular function	Low-density lipoprotein particle receptor binding	NAS	20005821
GO:0060228	Molecular function	Phosphatidylcholine-sterol O-acyltransferase activator activity	IBA	21873635
GO:0060228	Molecular function	Phosphatidylcholine-sterol O-acyltransferase activator activity	IDA	15654758
GO:0070326	Molecular function	Very-low-density lipoprotein particle receptor binding	IBA	21873635
GO:0070326	Molecular function	Very-low-density lipoprotein particle receptor binding	IDA	1384047
GO:0070326	Molecular function	Very-low-density lipoprotein particle receptor binding	IPI	12950167
GO:0120020	Molecular function	Intermembrane cholesterol transfer activity	IBA	21873635

Protein Information

Protein Name

Apolipoprotein E, apolipoprotein E3

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: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).

Refseq Proteins

NP_000032.1, NP_001289617.1, NP_001289618.1, NP_001289619.1, NP_001289620.1

UniProt

P02649

PDB

1B68, 1BZ4, 1EA8, 1GS9, 1H7I, 1LE2, 1LE4, 1LPE, 1NFN, 1NFO, 1OEF, 1OEG, 1OR2, 1OR3, 2KC3, 2KNY, 2L7B, 6NCN, 6NCO

Pfam

Pfam Accession	Pfam ID
PF01442	Apolipoprotein