APOE_HUMAN
Source:
hRBCD
; ID:
IPI00021842
PM19886704
PM23856902
Marked as 'Non-membrane protein'
Confidence:
medium (present in either hRBCD or BSc_CH or PM22954596)
Search PubMed for
(RBC AND this entry)
Gene names:
APOE
Protein names and data:
APOE_HUMAN
, Apolipoprotein E; Apo-E; Flags: Precursor
Lenght: 317 a.a.
Mass: 36154 Da
fasta formatted sequence
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.
Disease:
( OMIM:
104310
107741
143890
269600
611771
)
Hyperlipoproteinemia 3 (HLPP3) [MIM:107741]: A disorder characterized by the accumulation of intermediate-density lipoprotein particles (IDL or broad-beta-lipoprotein) rich in cholesterol. Clinical features include xanthomas, yellowish lipid deposits in the palmar crease, or less specific on tendons and on elbows. The disorder rarely manifests before the third decade in men. In women, it is usually expressed only after the menopause. Note=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. Alzheimer disease 2 (AD2) [MIM:104310]: 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. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. 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. Sea-blue histiocyte disease (SBHD) [MIM:269600]: Characterized by splenomegaly, mild thrombocytopenia and, in the bone marrow, numerous histiocytes containing cytoplasmic granules which stain bright blue with the usual hematologic stains. The syndrome is the consequence of an inherited metabolic defect analogous to Gaucher disease and other sphingolipidoses. Note=The disease is caused by mutations affecting the gene represented in this entry. Lipoprotein glomerulopathy (LPG) [MIM:611771]: Uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. Note=The disease is caused by mutations affecting the gene represented in this entry. Familial hypercholesterolemia (FH) [MIM:143890]: Common autosomal semi-dominant disease that affects about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis). Note=The disease is caused by mutations affecting the gene represented in this entry.
Cellular 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.
Genetic variants
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.
21 - 21
E -> K (in form E5; associated with hyperlipoproteinemia and atherosclerosis). VAR_000645
31 - 31
E -> K (in HLPP3; form E4 Philadelphia and form E5-type; only form E4 Philadelphia is disease-linked; dbSNP:rs201672011). VAR_000646
201672011
43 - 43
R -> C (in LPG; form E2 Kyoto). VAR_042734
46 - 46
L -> P (in form E4 Freiburg; dbSNP:rs769452). VAR_000647
769452
60 - 60
T -> A (in form E3 Freiburg; dbSNP:rs28931576). VAR_000648
28931576
64 - 64
Q -> H (polymorphism confirmed at protein level). VAR_014114
99 - 99
Q -> K (in form E5 Frankfurt). VAR_000649
102 - 102
P -> R (in form E5-type; no hyperlipidemia; dbSNP:rs28931578). VAR_000650
28931578
117 - 117
A -> T (in form E3*; dbSNP:rs28931577). VAR_000651
28931577
124 - 124
A -> V (in form E3 Basel). VAR_016789
130 - 130
C -> R (in HLPP3; form E3**, form E4, form E4/3 and some forms E5-type; only form E3** is disease-linked; dbSNP:rs429358). VAR_000652
429358
145 - 145
G -> D (in form E1 Weisgraber). VAR_000653
145 - 145
G -> GEVQAMLG (in HLPP3; form E3 Leiden). VAR_000654
152 - 152
R -> Q (in form E2-type; no hyperlipidemia; dbSNP:rs28931578). VAR_000655
28931578
154 - 154
R -> C (in HLPP3; form E2-type). VAR_000657
154 - 154
R -> S (in HLPP3; form E2 Christchurch). VAR_000656
160 - 160
R -> C (in HLPP3; form E3**). VAR_000658
163 - 163
R -> C (in HLPP3; form E4 Philadelphia and form E2-type; only form E4 Philadelphia is disease-linked; dbSNP:rs769455). VAR_000659
769455
163 - 163
R -> H (in E3 Kochi). VAR_000660
163 - 163
R -> P (in LPG; form E2 Sendai). VAR_042735
164 - 164
K -> E (in HLPP3; form E1 Harrisburg). VAR_000662
164 - 164
K -> Q (in HLPP3; form E2**). VAR_000661
167 - 167
Missing (in SBHD and FH; also found in patients with a diagnosis of familial combined hyperlipidemia). VAR_035015
170 - 170
A -> P (in form E3*). VAR_000663
176 - 176
R -> C (in HLPP3; forms E1 Weisgraber, form E2 and form E3**; dbSNP:rs7412). VAR_000664
7412
242 - 242
R -> Q (in form E2 Fukuoka). VAR_000665
246 - 246
R -> C (in form E2 Dunedin). VAR_000666
254 - 254
V -> E (in form E2 W.G.). VAR_000667
262 - 263
EE -> KK (in HLPP3; form E7 Suita). VAR_000668
269 - 269
R -> G (in form E3 H.B. and isoform E4/ 3). VAR_000669
270 - 270
L -> E (in form E1 H.E.; requires 2 nucleotide substitutions). VAR_000670
292 - 292
R -> H (in form E4 P.D.). VAR_000671
314 - 314
S -> R (in form E4 H.G.; dbSNP:rs28931579). VAR_000672
28931579
Database cross-references
UniProt:
P02649
Ensembl:
ENST00000252486
MIM:
104310
MIM:
107741
MIM:
143890
MIM:
269600
MIM:
611771
neXtProt:
NX_P02649
Antibodypedia:
P02649
(may not find the protein thus also not any antibody)
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