Apolipoprotein E3 (APOE3) Human Active Protein

APOE: 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.

Protein type: Lipid-binding; Secreted; Secreted, signal peptide

Chromosomal Location of Human Ortholog: 19q13.2

Cellular Component: chylomicron; cytoplasm; early endosome; endoplasmic reticulum; extracellular matrix; extracellular region; extracellular space; Golgi apparatus; membrane; nucleus; plasma membrane

Molecular Function: antioxidant activity; beta-amyloid binding; cholesterol binding; cholesterol transporter activity; heparin binding; identical protein binding; lipid binding; lipid transporter activity; low-density lipoprotein receptor binding; metal chelating activity; phospholipid binding; protein binding; protein homodimerization activity; tau protein binding

Biological Process: cGMP-mediated signaling; cholesterol catabolic process; cholesterol efflux; cholesterol homeostasis; cholesterol metabolic process; cytoskeleton organization and biogenesis; fatty acid homeostasis; G-protein coupled receptor protein signaling pathway; intracellular transport; lipoprotein catabolic process; lipoprotein metabolic process; long-chain fatty acid transport; negative regulation of blood coagulation; negative regulation of blood vessel endothelial cell migration; negative regulation of cholesterol biosynthetic process; negative regulation of endothelial cell proliferation; negative regulation of inflammatory response; negative regulation of MAP kinase activity; negative regulation of neuron apoptosis; neurite regeneration; nitric oxide mediated signal transduction; phospholipid efflux; positive regulation of cGMP biosynthetic process; positive regulation of lipid biosynthetic process; positive regulation of low-density lipoprotein receptor catabolic process; positive regulation of membrane protein ectodomain proteolysis; positive regulation of nitric-oxide synthase activity; protein import; receptor-mediated endocytosis; regulation of axon extension; regulation of Cdc42 protein signal transduction; regulation of neuronal synaptic plasticity; retinoid metabolic process; reverse cholesterol transport; synaptic transmission, cholinergic; triacylglycerol catabolic process; triacylglycerol metabolic process; virus assembly

Disease: Alzheimer Disease 2; Alzheimer Disease 4; Lipoprotein Glomerulopathy; Macular Degeneration, Age-related, 1; Sea-blue Histiocyte Disease