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FLASH GENE

Symbol

APOE

contributors: mct/pgu - updated : 14-12-2009

HGNC name	apolipoprotein E
HGNC id	613

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	AD2 Alzheimer disease associated with APOE4 APOE familial dysbetalipoproteinemia, hyperlipoproteinemia type III ARMDS2 age related macular dystrophy, 2 SBHD sea-blue histiocyte disease
Location	19q13.32      Physical location : 45.409.038 - 45.412.649
Synonym name	apoprotein
	apolipoprotein E3
	Alzheimer disease 2 (APOE*E4-associated, late onset)
Synonym symbol(s)	MGC1571, Apo-E, LPG, LDLCQ5

DNA

TYPE	functioning gene
STRUCTURE	3.61 kb     4 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

Physical map

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed APOE3 - - - - - - 2010 21114327 exhibits lower lipid binding ability than APOE4 as a consequence of a rearrangement involving the segment spanning AAs 261-272 in the C-terminal domain APOE4 binds less strongly than APOE3 to HDL(3), consistent with apoE-lipid interactions being relatively unimportant for binding to HDL at residues 112 or 158, apoE3 has a cysteine at residue 112 and an arginine at residue 158 APOE4 - - - - 299 - 2010 21114327 exhibits better lipid binding ability than APOE3 as a consequence of a rearrangement involving the segment spanning AAs 261-272 stronger lipid binding ability of APOE4 relative to that of APOE3 differs from the other two common isoforms (apoE2, apoE3) at residues 112 or 158, having arginines at both positions may perturb mitochondrial respiratory function in the brain, rendering subjects with apoE4 more susceptible to AD neuropathology detrimental effects of apoE4 on mitochondria can be mitigated by genetic and pharmacologic interference with apoE4 domain interaction NM_000041 4 - 1223 34.2 317 - 2005 16091415 with two alternative stop codons variant 3 - - 5515 isoform 3 - - liver 2005 16091415 also called APOEAS2 variant 2 - - - isoform 2 - 219 parotis, kidney, liver, lung, thymus, small intestine 2005 16091415 also called APOEAS1 antisense transcript APOE2 - - - - - - 2011 21118811 at residues 112 or 158 having cysteines

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver       highly Endocrine adrenal gland       highly Lymphoid/Immune spleen       moderately Nervous brain       predominantly Homo sapiens Reproductive female system ovary     moderately Respiratory lung       moderately Urinary kidney       highly Visual eye retina     moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining retinal pigment epithelium (RPE)

cells

System Cell Pubmed Species Stage Rna symbol Nervous astrocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N-terminal domain of interaction with the LDL receptor and heparin sulfate proteoglycan
	a hinge region from the C-terminal lipid binding domain
	an heparin binding region

conjugated

GlycoP

HOMOLOGY

interspecies	homolog to rattus Apoe (71.34 pc)
	homolog to murine Apoe (73.70 pc)

intraspecies

homolog to APOA4

Homologene

FAMILY

APOA1/APOA4/APOE family

CATEGORY

receptor membrane , transport carrier

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm

basic FUNCTION	clearance of chylomicrons, remnants and beta-VLDL from the plasma
	in the nervous system, functions as a major carrier and distributor of cholesterol and other lipids, which are essential components of neuronal membranes and myelin sheaths
	role of APOE and COMT genes in prospective and retrospective memory traits

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

lipid/lipoprotein

signaling

sensory transduction/vision

fatty acid and sterol

a component

constituent of several lipoproteins including chylomicrons, remnants, VLDL, IDL, some HDLs

INTERACTION

DNA

RNA

small molecule

protein	binding to LDL receptor
	binding with MYOC promoter SNP (increased intraocular pressure in primary open angle glaucoma
	binding to heparin
	APOE4 binds preferentially to very low-density lipoproteins (VLDLs), whereas APOE3 binds preferentially to high-density lipoproteins (HDLs), resulting in different plasma cholesterol levels for the two isoforms

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

APOE , ARMDS2 , SBHD , AD2

Susceptibility

putative susceptibility factor (epsilon 4 allele) for agressive multiple sclerosis, for early-onset coronary heart disease and Alzheimer's diseases (AD2) susceptibility factor (epsilon 2/3/4 allele) for dementia (in old age) susceptibility for AMD (age related macular dystrophy) (e2/e2 allele increased risk) suceptibility (epsilon 2 allele) to frontotemporal dementia and to myocardial infarction susceptibility to Alzheimer disease 2 (AD2) to ischemic heart disease

Variant & Polymorphism SNP , other	(-219G) associated with increased optic nerve damage in primery open angle glaucoma
	epsilon 2 allele by mother correlated with Smith-Lemli-Opitz severe form
	combinations of SNPs in APOE and LPL identify subgroups of individuals at substantially increased risk of ischemic heart disease
	APOE haplotypes common, found to be significantly associated with AMD, G-G-G-G-epsilon2, T-C-G-G-epsilon3 and T-G-A-G-epsilon4

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative alzheimer pharmacological intervention with small molecules that disrupt apoE4 domain interaction is a potential therapeutic approach for apoE4-carrying AD subjects

ANIMAL & CELL MODELS