APOE a secreted apolipoprotein that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids. Specific alleles influence the development of Alzheimer's Disease (AD). Humans express three alleles: APOE2, -E3 and -E4, and six genotypes — E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, or E4/E4. The E2 allele is the rarest form and reduces the risk of developing Alzheimer's. APOE3 is the most common allele and doesn't seem to influence AD risk. The E4 allele, present in approximately 10-15% of people, increases the risk for AD and lowers the age of onset. Having one copy of E4 can increase your risk 2 to 3 fold while two copies (E4/E4) can increase the risk 12 fold. APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance. Apoliproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma. As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL). It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles. Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells. A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes. APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of triglycerides and energy storage in muscle, heart and adipose tissues. APOE is also involved in two steps of reverse cholesterol transport, the HDLs-mediated transport of cholesterol from peripheral tissues to the liver, and thereby plays an important role in cholesterol homeostasis. First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues. Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes. APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting. APOE in also involved in innate and adaptive immune responses, controlling for instance the survival of myeloid-derived suppressor cells. Belongs to the apolipoprotein A1/A4/E family. Produced by several tissues and cell types and mainly found associated with lipid particles in the plasma, the interstitial fluid and lymph. Mainly synthesized by liver hepatocytes. Significant quantities are also produced in brain, mainly by astrocytes and glial cells in the cerebral cortex, but also by neurons in frontal cortex and hippocampus. It is also expressed by cells of the peripheral nervous system. Also expressed by adrenal gland, testis, ovary, skin, kidney, spleen and adipose tissue and macrophages in various tissues. Note: This description may include information from UniProtKB.
Protein type: Lipid-binding; Secreted; Secreted, signal peptide
Chromosomal Location of Human Ortholog: 19q13.32
Cellular Component:  chylomicron; clathrin-coated endocytic vesicle membrane; cytoplasm; dendrite; discoidal high-density lipoprotein particle; early endosome; endocytic vesicle lumen; endoplasmic reticulum; endoplasmic reticulum lumen; extracellular matrix; extracellular region; extracellular space; glutamatergic synapse; Golgi apparatus; high-density lipoprotein particle; intermediate-density lipoprotein particle; lipoprotein particle; low-density lipoprotein particle; neuronal cell body; plasma membrane; synaptic cleft; very-low-density lipoprotein particle
Molecular Function:  amyloid-beta binding; antioxidant activity; heparan sulfate proteoglycan binding; heparin binding; identical protein binding; lipid binding; lipid transporter activity; lipoprotein particle binding; low-density lipoprotein particle receptor binding; metal chelating activity; phosphatidylcholine-sterol O-acyltransferase activator activity; phospholipid binding; protein binding; protein dimerization activity; protein homodimerization activity; protein-containing complex binding; signaling receptor binding; structural molecule activity; tau protein binding; very-low-density lipoprotein particle receptor binding
Biological Process:  AMPA glutamate receptor clustering; amyloid precursor protein metabolic process; artery morphogenesis; cellular calcium ion homeostasis; cellular oxidant detoxification; cellular protein metabolic process; cGMP-mediated signaling; cholesterol efflux; cholesterol homeostasis; cholesterol metabolic process; chylomicron assembly; chylomicron remnant clearance; chylomicron remodeling; cytoskeleton organization; fatty acid homeostasis; G protein-coupled receptor signaling pathway; high-density lipoprotein particle assembly; high-density lipoprotein particle clearance; high-density lipoprotein particle remodeling; intermediate-density lipoprotein particle clearance; intracellular transport; lipid transport involved in lipid storage; lipoprotein biosynthetic process; locomotory exploration behavior; long-chain fatty acid transport; long-term memory; low-density lipoprotein particle remodeling; maintenance of location in cell; negative regulation of amyloid fibril formation; negative regulation of amyloid-beta formation; negative regulation of blood coagulation; negative regulation of blood vessel endothelial cell migration; negative regulation of canonical Wnt signaling pathway; negative regulation of cellular protein metabolic process; negative regulation of cholesterol biosynthetic process; negative regulation of endothelial cell migration; negative regulation of endothelial cell proliferation; negative regulation of gene expression; negative regulation of inflammatory response; negative regulation of long-term synaptic potentiation; negative regulation of MAP kinase activity; negative regulation of neuron death; negative regulation of neuron projection development; negative regulation of platelet activation; negative regulation of presynaptic membrane organization; negative regulation of protein secretion; negative regulation of triglyceride metabolic process; neuron projection development; nitric oxide mediated signal transduction; NMDA glutamate receptor clustering; phospholipid efflux; positive regulation by host of viral process; positive regulation of amyloid fibril formation; positive regulation of amyloid-beta clearance; positive regulation of cholesterol efflux; positive regulation of cholesterol esterification; positive regulation of dendritic spine development; positive regulation of dendritic spine maintenance; positive regulation of endocytosis; positive regulation of ERK1 and ERK2 cascade; positive regulation of heparan sulfate binding; positive regulation of heparan sulfate proteoglycan binding; positive regulation of lipid biosynthetic process; positive regulation of lipid transport across blood brain barrier; positive regulation of low-density lipoprotein particle receptor catabolic process; positive regulation of membrane protein ectodomain proteolysis; positive regulation of neuron projection development; positive regulation of nitric-oxide synthase activity; positive regulation of phospholipid efflux; positive regulation of postsynaptic membrane organization; positive regulation of transcription, DNA-templated; post-translational protein modification; protein import; receptor-mediated endocytosis; regulation of amyloid fibril formation; regulation of amyloid-beta clearance; regulation of axon extension; regulation of behavioral fear response; regulation of Cdc42 protein signal transduction; regulation of cellular response to very-low-density lipoprotein particle stimulus; regulation of cholesterol metabolic process; regulation of innate immune response; regulation of neuronal synaptic plasticity; regulation of proteasomal protein catabolic process; regulation of protein homooligomerization; regulation of protein metabolic process; regulation of transcription by RNA polymerase II; response to caloric restriction; response to dietary excess; response to reactive oxygen species; retinoid metabolic process; reverse cholesterol transport; synaptic transmission, cholinergic; triglyceride homeostasis; triglyceride metabolic process; triglyceride-rich lipoprotein particle clearance; vasodilation; very-low-density lipoprotein particle clearance; very-low-density lipoprotein particle remodeling; virion assembly
Disease: Alzheimer Disease 2; Alzheimer Disease 4; Hyperlipoproteinemia, Type Iii; Lipoprotein Glomerulopathy; Macular Degeneration, Age-related, 1; Sea-blue Histiocyte Disease
Reference #:  P02649 (UniProtKB)
Alt. Names/Synonyms: AD2; Apo-E; APOE; Apolipoprotein E; LDLCQ5; LPG; MGC1571
Gene Symbols: APOE
Molecular weight: 36,154 Da
Basal Isoelectric point: 5.65  Predict pI for various phosphorylation states
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

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