Gene/Proteome Database (LMPD)

LMPD ID
LMP000386
Gene ID
348
Species
Homo sapiens (Human)
Gene Name
apolipoprotein E
Gene Symbol
APOE
Synonyms
AD2; APO-E; LDLCQ5; LPG
Alternate Names
apolipoprotein E; apolipoprotein E3
Chromosome
19
Map Location
19q13.2
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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]
Orthologs
View orthologs and multiple alignments for APOE

Proteins

apolipoprotein E isoform b precursor
Refseq ID NP_000032
Protein GI 4557325
UniProt ID P02649
mRNA ID NM_000041
Length 317
RefSeq Status REVIEWED
MKVLWAALLVTFLAGCQAKVEQAVETEPEPELRQQTEWQSGQRWELALGRFWDYLRWVQTLSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQARLGADMEDVCGRLVQYRGEVQAMLGQSTEELRVRLASHLRKLRKRLLRDADDLQKRLAVYQAGAREGAERGLSAIRERLGPLVEQGRVRAATVGSLAGQPLQERAQAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGTSAAPVPSDNH
apolipoprotein E isoform b precursor
Refseq ID NP_001289620
Protein GI 705044152
UniProt ID P02649
mRNA ID NM_001302691
Length 317
RefSeq Status REVIEWED
Protein sequence is identical to GI:4557325 (mRNA isoform)
sig_peptide: 1..18 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 1935 peptide sequence: MKVLWAALLVTFLAGCQA mat_peptide: 19..317 product: Apolipoprotein E experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P02649.1) calculated_mol_wt: 34237 peptide sequence: KVEQAVETEPEPELRQQTEWQSGQRWELALGRFWDYLRWVQTLSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQARLGADMEDVCGRLVQYRGEVQAMLGQSTEELRVRLASHLRKLRKRLLRDADDLQKRLAVYQAGAREGAERGLSAIRERLGPLVEQGRVRAATVGSLAGQPLQERAQAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGTSAAPVPSDNH sig_peptide: 1..44 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 4829 peptide sequence: MSSGASRKSWDPGNPWPPDWPITGRKMKVLWAALLVTFLAGCQA sig_peptide: 1..18 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 1935 peptide sequence: MKVLWAALLVTFLAGCQA mat_peptide: 19..317 product: Apolipoprotein E experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P02649.1) calculated_mol_wt: 34237 peptide sequence: KVEQAVETEPEPELRQQTEWQSGQRWELALGRFWDYLRWVQTLSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQARLGADMEDVCGRLVQYRGEVQAMLGQSTEELRVRLASHLRKLRKRLLRDADDLQKRLAVYQAGAREGAERGLSAIRERLGPLVEQGRVRAATVGSLAGQPLQERAQAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGTSAAPVPSDNH sig_peptide: 1..18 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 1935 peptide sequence: MKVLWAALLVTFLAGCQA mat_peptide: 19..317 product: Apolipoprotein E experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P02649.1) calculated_mol_wt: 34237 peptide sequence: KVEQAVETEPEPELRQQTEWQSGQRWELALGRFWDYLRWVQTLSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQARLGADMEDVCGRLVQYRGEVQAMLGQSTEELRVRLASHLRKLRKRLLRDADDLQKRLAVYQAGAREGAERGLSAIRERLGPLVEQGRVRAATVGSLAGQPLQERAQAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGTSAAPVPSDNH sig_peptide: 1..18 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 1935 peptide sequence: MKVLWAALLVTFLAGCQA mat_peptide: 19..317 product: Apolipoprotein E experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P02649.1) calculated_mol_wt: 34237 peptide sequence: KVEQAVETEPEPELRQQTEWQSGQRWELALGRFWDYLRWVQTLSEQVQEELLSSQVTQELRALMDETMKELKAYKSELEEQLTPVAEETRARLSKELQAAQARLGADMEDVCGRLVQYRGEVQAMLGQSTEELRVRLASHLRKLRKRLLRDADDLQKRLAVYQAGAREGAERGLSAIRERLGPLVEQGRVRAATVGSLAGQPLQERAQAWGERLRARMEEMGSRTRDRLDEVKEQVAEVRAKLEEQAQQIRLQAEAFQARLKSWFEPLVEDMQRQWAGLVEKVQAAVGTSAAPVPSDNH

Gene Information

Entrez Gene ID
348
Gene Name
apolipoprotein E
Gene Symbol
APOE
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0072562 IDA:UniProt C blood microparticle
GO:0042627 IDA:BHF-UCL C chylomicron
GO:0005737 TAS:UniProtKB C cytoplasm
GO:0030425 NAS:BHF-UCL C dendrite
GO:0005769 TAS:Reactome C early endosome
GO:0071682 TAS:Reactome C endocytic vesicle lumen
GO:0031012 IDA:UniProtKB C extracellular matrix
GO:0005576 TAS:Reactome C extracellular region
GO:0005615 IDA:BHF-UCL C extracellular space
GO:0070062 IDA:UniProtKB C extracellular vesicular exosome
GO:0031232 IEA:Ensembl C extrinsic component of external side of plasma membrane
GO:0005794 IEA:Ensembl C Golgi apparatus
GO:0034364 IDA:BHF-UCL C high-density lipoprotein particle
GO:0034363 IDA:BHF-UCL C intermediate-density lipoprotein particle
GO:0005770 IEA:Ensembl C late endosome
GO:0034362 IDA:BHF-UCL C low-density lipoprotein particle
GO:0016020 IDA:UniProtKB C membrane
GO:0043025 NAS:BHF-UCL C neuronal cell body
GO:0005634 IDA:UniProt C nucleus
GO:0005886 TAS:Reactome C plasma membrane
GO:0034361 IDA:BHF-UCL C very-low-density lipoprotein particle
GO:0031982 IDA:UniProtKB C vesicle
GO:0016209 IDA:BHF-UCL F antioxidant activity
GO:0001540 IDA:UniProtKB F beta-amyloid binding
GO:0017127 IEA:Ensembl F cholesterol transporter activity
GO:0008201 IDA:BHF-UCL F heparin binding
GO:0046848 IEA:Ensembl F hydroxyapatite binding
GO:0042802 IDA:BHF-UCL F identical protein binding
GO:0008289 IDA:UniProtKB F lipid binding
GO:0005319 IDA:BHF-UCL F lipid transporter activity
GO:0071813 IEA:Ensembl F lipoprotein particle binding
GO:0050750 IDA:BHF-UCL F low-density lipoprotein particle receptor binding
GO:0046911 IDA:BHF-UCL F metal chelating activity
GO:0060228 IDA:BHF-UCL F phosphatidylcholine-sterol O-acyltransferase activator activity
GO:0005543 IDA:BHF-UCL F phospholipid binding
GO:0042803 IPI:BHF-UCL F protein homodimerization activity
GO:0048156 IPI:BHF-UCL F tau protein binding
GO:0070326 IDA:BHF-UCL F very-low-density lipoprotein particle receptor binding
GO:0007568 IEA:Ensembl P aging
GO:0097113 IDA:Alzheimers_University_of_Toronto P alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor clustering
GO:0048844 IEA:Ensembl P artery morphogenesis
GO:0008219 IEA:UniProtKB-KW P cell death
GO:0006874 IEA:Ensembl P cellular calcium ion homeostasis
GO:0071397 IEA:Ensembl P cellular response to cholesterol
GO:0071363 IEA:Ensembl P cellular response to growth factor stimulus
GO:0071347 IEA:Ensembl P cellular response to interleukin-1
GO:0019934 IDA:BHF-UCL P cGMP-mediated signaling
GO:0006707 IEA:Ensembl P cholesterol catabolic process
GO:0033344 IDA:BHF-UCL P cholesterol efflux
GO:0042632 IDA:BHF-UCL P cholesterol homeostasis
GO:0008203 IDA:BHF-UCL P cholesterol metabolic process
GO:0034382 IMP:BHF-UCL P chylomicron remnant clearance
GO:0007010 TAS:UniProtKB P cytoskeleton organization
GO:0055089 IDA:Alzheimers_University_of_Toronto P fatty acid homeostasis
GO:0007186 IDA:BHF-UCL P G-protein coupled receptor signaling pathway
GO:0034380 IDA:BHF-UCL P high-density lipoprotein particle assembly
GO:0034384 IDA:BHF-UCL P high-density lipoprotein particle clearance
GO:0034375 IGI:BHF-UCL P high-density lipoprotein particle remodeling
GO:0046907 TAS:UniProtKB P intracellular transport
GO:0042158 IEA:Ensembl P lipoprotein biosynthetic process
GO:0042159 IEA:Ensembl P lipoprotein catabolic process
GO:0042157 TAS:Reactome P lipoprotein metabolic process
GO:0015909 IDA:Alzheimers_University_of_Toronto P long-chain fatty acid transport
GO:0034374 IEA:Ensembl P low-density lipoprotein particle remodeling
GO:0051651 IEA:Ensembl P maintenance of location in cell
GO:1902430 IDA:Alzheimers_University_of_Toronto P negative regulation of beta-amyloid formation
GO:0030195 IDA:BHF-UCL P negative regulation of blood coagulation
GO:0043537 IDA:BHF-UCL P negative regulation of blood vessel endothelial cell migration
GO:0045541 IDA:BHF-UCL P negative regulation of cholesterol biosynthetic process
GO:0090370 IDA:Alzheimers_University_of_Toronto P negative regulation of cholesterol efflux
GO:0061000 IDA:Alzheimers_University_of_Toronto P negative regulation of dendritic spine development
GO:1902951 IDA:Alzheimers_University_of_Toronto P negative regulation of dendritic spine maintenance
GO:0001937 IDA:BHF-UCL P negative regulation of endothelial cell proliferation
GO:0050728 IC:BHF-UCL P negative regulation of inflammatory response
GO:0051055 IDA:Alzheimers_University_of_Toronto P negative regulation of lipid biosynthetic process
GO:1903001 IDA:Alzheimers_University_of_Toronto P negative regulation of lipid transport across blood brain barrier
GO:0043407 IDA:BHF-UCL P negative regulation of MAP kinase activity
GO:0043524 IEA:Ensembl P negative regulation of neuron apoptotic process
GO:1901215 IDA:Alzheimers_University_of_Toronto P negative regulation of neuron death
GO:1902999 IDA:Alzheimers_University_of_Toronto P negative regulation of phospholipid efflux
GO:0010544 IDA:BHF-UCL P negative regulation of platelet activation
GO:1901627 IDA:Alzheimers_University_of_Toronto P negative regulation of postsynaptic membrane organization
GO:1901630 IDA:Alzheimers_University_of_Toronto P negative regulation of presynaptic membrane organization
GO:0007263 IDA:BHF-UCL P nitric oxide mediated signal transduction
GO:0097114 IDA:Alzheimers_University_of_Toronto P N-methyl-D-aspartate receptor clustering
GO:0048709 IEA:Ensembl P oligodendrocyte differentiation
GO:0014012 IEA:Ensembl P peripheral nervous system axon regeneration
GO:0033700 IDA:BHF-UCL P phospholipid efflux
GO:0007603 TAS:Reactome P phototransduction, visible light
GO:0045773 IEA:Ensembl P positive regulation of axon extension
GO:1902004 IDA:Alzheimers_University_of_Toronto P positive regulation of beta-amyloid formation
GO:0030828 IDA:BHF-UCL P positive regulation of cGMP biosynthetic process
GO:0010875 IDA:Alzheimers_University_of_Toronto P positive regulation of cholesterol efflux
GO:0010873 IDA:BHF-UCL P positive regulation of cholesterol esterification
GO:0060999 IDA:Alzheimers_University_of_Toronto P positive regulation of dendritic spine development
GO:1902952 IDA:Alzheimers_University_of_Toronto P positive regulation of dendritic spine maintenance
GO:0046889 IDA:Alzheimers_University_of_Toronto P positive regulation of lipid biosynthetic process
GO:1903002 IDA:Alzheimers_University_of_Toronto P positive regulation of lipid transport across blood brain barrier
GO:0032805 IDA:BHF-UCL P positive regulation of low-density lipoprotein particle receptor catabolic process
GO:0051044 IDA:BHF-UCL P positive regulation of membrane protein ectodomain proteolysis
GO:1902998 IDA:Alzheimers_University_of_Toronto P positive regulation of neurofibrillary tangle assembly
GO:1901216 IDA:Alzheimers_University_of_Toronto P positive regulation of neuron death
GO:0051000 IDA:BHF-UCL P positive regulation of nitric-oxide synthase activity
GO:1902995 IDA:Alzheimers_University_of_Toronto P positive regulation of phospholipid efflux
GO:1901628 IDA:Alzheimers_University_of_Toronto P positive regulation of postsynaptic membrane organization
GO:1901631 IDA:Alzheimers_University_of_Toronto P positive regulation of presynaptic membrane organization
GO:0017038 IDA:Alzheimers_University_of_Toronto P protein import
GO:0006898 IDA:BHF-UCL P receptor-mediated endocytosis
GO:0030516 TAS:UniProtKB P regulation of axon extension
GO:1900221 IDA:Alzheimers_University_of_Toronto P regulation of beta-amyloid clearance
GO:0032489 IDA:BHF-UCL P regulation of Cdc42 protein signal transduction
GO:0048168 TAS:UniProtKB P regulation of neuronal synaptic plasticity
GO:1901214 IDA:Alzheimers_University_of_Toronto P regulation of neuron death
GO:1902947 IDA:Alzheimers_University_of_Toronto P regulation of tau-protein kinase activity
GO:0002021 IEA:Ensembl P response to dietary excess
GO:0045471 IEA:Ensembl P response to ethanol
GO:0032868 IEA:Ensembl P response to insulin
GO:0000302 NAS:UniProtKB P response to reactive oxygen species
GO:0032526 IEA:Ensembl P response to retinoic acid
GO:0001523 TAS:Reactome P retinoid metabolic process
GO:0043691 IDA:BHF-UCL P reverse cholesterol transport
GO:0044281 TAS:Reactome P small molecule metabolic process
GO:0007271 TAS:UniProtKB P synaptic transmission, cholinergic
GO:0006641 IDA:BHF-UCL P triglyceride metabolic process
GO:0042311 IEA:Ensembl P vasodilation
GO:0034447 IDA:BHF-UCL P very-low-density lipoprotein particle clearance
GO:0034372 IDA:BHF-UCL P very-low-density lipoprotein particle remodeling

KEGG Pathway Links

KEGG Pathway ID Description
hsa05010 Alzheimer's disease

REACTOME Pathway Links

REACTOME Pathway ID Description
REACT_163699 Scavenging by Class A Receptors

Domain Information

InterPro Annotations

Accession Description
IPR000074 Apolipoprotein A/E

UniProt Annotations

Entry Information

Gene Name
apolipoprotein E
Protein Entry
APOE_HUMAN
UniProt ID
P02649
Species
Human

Comments

Comment Type Description
Disease Alzheimer disease 2 (AD2) [MIM
Disease Familial hypercholesterolemia (FH) [MIM
Disease Hyperlipoproteinemia 3 (HLPP3) [MIM
Disease Lipoprotein glomerulopathy (LPG) [MIM
Disease Sea-blue histiocyte disease (SBHD) [MIM
Function Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues.
Interaction Q16543:CDC37; NbExp=3; IntAct=EBI-1222467, EBI-295634; Q9BQ95:ECSIT; NbExp=4; IntAct=EBI-1222467, EBI-712452; P00738:HP; NbExp=7; IntAct=EBI-1222467, EBI-1220767; P01130:LDLR; NbExp=2; IntAct=EBI-1222467, EBI-988319; Q14114:LRP8; NbExp=2; IntAct=EBI-1222467, EBI-2681187; P10636:MAPT; NbExp=3; IntAct=EBI-9209835, EBI-366182; Q53EL6:PDCD4; NbExp=3; IntAct=EBI-1222467, EBI-935824; P50502:ST13; NbExp=3; IntAct=EBI-1222467, EBI-357285; O75069:TMCC2; NbExp=5; IntAct=EBI-1222467, EBI-726731;
Polymorphism Three common APOE alleles have been identified: APOE*2, APOE*3, and APOE*4. The corresponding three major isoforms, E2, E3, and E4, are recognized according to their relative position after isoelectric focusing. Different mutations causing the same migration pattern after isoelectric focusing define different isoform subtypes. The most common isoform is E3 and is present in 40-90% of the population. Common APOE variants influence lipoprotein metabolism in healthy individuals.
Ptm Glycated in plasma VLDL of normal subjects, and of hyperglycemic diabetic patients at a higher level (2-3 fold).
Ptm Phosphorylation sites are present in the extracellular medium.
Ptm Synthesized with the sialic acid attached by O-glycosidic linkage and is subsequently desialylated in plasma. O-glycosylated with core 1 or possibly core 8 glycans. Thr-307 and Thr-314 are minor glycosylation siteS compared to Ser-308.
Similarity Belongs to the apolipoprotein A1/A4/E family.
Subcellular Location Secreted.
Tissue Specificity Occurs in all lipoprotein fractions in plasma. It constitutes 10-20% of very low density lipoproteins (VLDL) and 1-2% of high density lipoproteins (HDL). APOE is produced in most organs. Significant quantities are produced in liver, brain, spleen, lung, adrenal, ovary, kidney and muscle.
Web Resource Name=Protein Spotlight; Note=Tangled - Issue 83 of June 2007; URL="http://web.expasy.org/spotlight/back_issues/083";
Web Resource Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=APOE";
Web Resource Name=Wikipedia; Note=Apolipoprotein E entry; URL="http://en.wikipedia.org/wiki/Apolipoprotein_E";

Identical and Related Proteins

Unique RefSeq proteins for LMP000386 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
4557325 RefSeq NP_000032 317 apolipoprotein E isoform b precursor

Identical Sequences to LMP000386 proteins

Reference Database Accession Length Protein Name
GI:4557325 GenBank AGY19288.1 317 Sequence 27 from patent US 8546643
GI:4557325 GenBank AHH58306.1 317 Sequence 51 from patent US 8617877
GI:4557325 GenBank AIC62442.1 317 APOE, partial [synthetic construct]
GI:4557325 RefSeq NP_001289618.1 317 apolipoprotein E isoform b precursor [Homo sapiens]
GI:4557325 RefSeq NP_001289619.1 317 apolipoprotein E isoform b precursor [Homo sapiens]
GI:4557325 RefSeq NP_001289620.1 317 apolipoprotein E isoform b precursor [Homo sapiens]

Related Sequences to LMP000386 proteins

Reference Database Accession Length Protein Name
GI:4557325 GenBank AAU97579.1 316 Sequence 247 from patent US 6727066
GI:4557325 GenBank ADA33818.1 317 Sequence 167 from patent US 7612179
GI:4557325 GenBank AEU48023.1 317 Sequence 167 from patent US 8058016
GI:4557325 GenBank AGB62527.1 354 Sequence 88 from patent US 8288091
GI:4557325 PRF - 317 apolipoprotein E mutant E3K [Homo sapiens]
GI:4557325 RefSeq NP_001289617.1 343 apolipoprotein E isoform a precursor [Homo sapiens]