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Protein Page:
APOE iso4 (human)
p Phosphorylation
a Acetylation
m Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
u Ubiquitination
s Sumoylation
n Neddylation
gl O-GlcNAc
ga O-GalNAc
h Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage

Overview
APOE iso4 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. Defects in APOE are a cause of hyperlipoproteinemia type 3 (HLPP3); also known as familial dysbetalipoproteinemia. Individuals with HLPP3 are clinically characterized by 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. 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. Genetic variations in APOE are associated with Alzheimer disease type 2 (AD2). It is a late-onset neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death. The APOE*4 allele is genetically associated with the common late onset familial and sporadic forms of Alzheimer disease. Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE*4 alleles in 42 families with late onset AD. Thus APOE*4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE*4 was virtually sufficient to cause AD by age 80. The mechanism by which APOE*4 participates in pathogenesis is not known. Defects in APOE are a cause of sea-blue histiocyte disease (SBHD); also known as sea-blue histiocytosis. This disorder is characterized by splenomegaly, mild thrombocytopenia and, in the bone marrow, numerous histiocytes containing cytoplasmic granules which stain bright blue with the usual hematologic stains. The syndrome is the consequence of an inherited metabolic defect analogous to Gaucher disease and other sphingolipidoses. Defects in APOE are a cause of lipoprotein glomerulopathy (LPG). LPG is an uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. It mainly affects people of Japanese and Chinese origin. The disorder has rarely been described in Caucasians. Belongs to the apolipoprotein A1/A4/E family. Note: This description may include information from UniProtKB.
Protein type: Lipid binding protein; Secreted, signal peptide; Secreted
Cellular Component: Golgi apparatus; extracellular space; chylomicron; extrinsic to external side of plasma membrane; cell soma; early endosome; cytoplasm; dendrite; late endosome; extracellular region; plasma membrane
Molecular Function: lipid transporter activity; heparin binding; identical protein binding; protein homodimerization activity; metal chelating activity; beta-amyloid binding; antioxidant activity; protein binding; low-density lipoprotein receptor binding; protein heterodimerization activity; cholesterol transporter activity; hydroxyapatite binding; phospholipid binding; lipid binding; tau protein binding
Biological Process: cell death; phototransduction, visible light; negative regulation of MAP kinase activity; response to dietary excess; lipoprotein catabolic process; cGMP-mediated signaling; positive regulation of axon extension; positive regulation of membrane protein ectodomain proteolysis; vasodilation; axon regeneration in the peripheral nervous system; response to insulin stimulus; synaptic transmission, cholinergic; positive regulation of low-density lipoprotein receptor catabolic process; intracellular transport; phospholipid efflux; oligodendrocyte differentiation; negative regulation of neuron apoptosis; retinoid metabolic process; negative regulation of cholesterol biosynthetic process; cholesterol catabolic process; aging; cholesterol metabolic process; receptor-mediated endocytosis; response to retinoic acid; regulation of Cdc42 protein signal transduction; positive regulation of nitric-oxide synthase activity; negative regulation of blood coagulation; lipoprotein metabolic process; cytoskeleton organization and biogenesis; cholesterol efflux; regulation of axon extension; negative regulation of blood vessel endothelial cell migration; maintenance of cellular localization; cellular calcium ion homeostasis; G-protein coupled receptor protein signaling pathway; cholesterol homeostasis; response to reactive oxygen species; response to ethanol; triacylglycerol metabolic process; reverse cholesterol transport; positive regulation of cGMP biosynthetic process; regulation of gene expression; lipoprotein biosynthetic process; negative regulation of inflammatory response; negative regulation of endothelial cell proliferation; artery morphogenesis; nitric oxide mediated signal transduction; regulation of neuronal synaptic plasticity
Reference #:  P02649_VAR_000652 (UniProtKB)
Alt. Names/Synonyms: AD2; Apo-E; ApoE4; Apolipoprotein E; apolipoprotein E4; LDLCQ5; LPG; MGC1571
Gene Symbols: APOE
Molecular weight: 36,207 Da
Basal Isoelectric point: 5.81  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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APOE iso4

Protein Structure Not Found.


Scansite  |  Pfam  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene


Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

► Hide Isoforms
 
0 1 T36-ga EPELRQQtEWQSGQR
0 1 S94 KELKAYKSELEEQLT
0 2 K113 ETRARLSKELQAAQA
0 4 S147-p VQAMLGQsTEELRVR
0 1 T148 QAMLGQsTEELRVRL
0 2 Y180-p LQKRLAVyQAGAREG
0 1 Q181 QKRLAVyQAGAREGA
0 1 T212-ga QGRVRAAtVGsLAGQ
0 1 S215-ga VRAAtVGsLAGQPLQ
0 1 S241-p ARMEEMGsRTRDRLD
0 4 K260 QVAEVRAKLEEQAQQ
0 1 K280 EAFQARLKSWFEPLV
0 1 T307-ga KVQAAVGtsAAPVPs
0 1 S308-ga VQAAVGtsAAPVPsD
1 0 S314-p tsAAPVPsDNH____
0 1 S314-ga tsAAPVPsDNH____
  APOE iso2  
T36 EPELRQQTEWQSGQR
S94 KELKAYKSELEEQLT
K113 ETRARLSKELQAAQA
S147 VQAMLGQSTEELRVR
T148 QAMLGQSTEELRVRL
Y180 LQKCLAVYQAGAREG
Q181 QKCLAVYQAGAREGA
T212 QGRVRAATVGSLAGQ
S215 VRAATVGSLAGQPLQ
S241 ARMEEMGSRTRDRLD
K260 QVAEVRAKLEEQAQQ
K280 EAFQARLKSWFEPLV
T307 KVQAAVGTSAAPVPS
S308 VQAAVGTSAAPVPSD
S314 TSAAPVPSDNH____
S314 TSAAPVPSDNH____
  APOE iso4  
T36 EPELRQQTEWQSGQR
S94 KELKAYKSELEEQLT
K113 ETRARLSKELQAAQA
S147 VQAMLGQSTEELRVR
T148 QAMLGQSTEELRVRL
Y180 LQKRLAVYQAGAREG
Q181 QKRLAVYQAGAREGA
T212 QGRVRAATVGSLAGQ
S215 VRAATVGSLAGQPLQ
S241 ARMEEMGSRTRDRLD
K260 QVAEVRAKLEEQAQQ
K280 EAFQARLKSWFEPLV
T307 KVQAAVGTSAAPVPS
S308 VQAAVGTSAAPVPSD
S314 TSAAPVPSDNH____
S314 TSAAPVPSDNH____
  mouse

 
- gap
K86-u TEVKAYKkELEEQLG
K105-u ETRARLGkEVQAAQA
S139-p VHTMLGQstEEIRAR
T140-p HTMLGQstEEIRARL
Y172 LQKRLAVYkAGAREG
K173-u QKRLAVYkAGAREGA
N204 QGRQRTANLGAGAAQ
A207 QRTANLGAGAAQPLR
N233 GRLEEVGNQARDRLE
K252-u HMEEVRSkMEEQTQQ
K272-u EIFQARLkGWFEPIV
T299 KIQASVATNPIITPV
N300 IQASVATNPIITPVA
- gap
- gap
  rat

 
- gap
K86 TEVKAYKKELEEQLG
K105 ETRARLAKEVQAAQA
S139-p VNTMLGQstEELRSR
T140-p NTMLGQstEELRSRL
Y172 LQKRLAVYKAGAQEG
K173 QKRLAVYKAGAQEGA
N204 QGRQRTANLGAGAAQ
A207 QRTANLGAGAAQPLR
N233 GRLEEVGNQARDRLE
K252 QMEEVRSKMEEQTQQ
K272 EIFQARIKGWFEPLV
T299 KIQASVATNSIASTT
N300 IQASVATNSIASTTV
- gap
- gap
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