APOC3
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 2JQ3
Identifiers
Aliases	APOC3, APOCIII, HALP2, apolipoprotein C3, Apo-C3, ApoC-3
External IDs	OMIM: 107720 HomoloGene: 81615 GeneCards: APOC3
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q23.3 Start 116,829,706 bp[1] End 116,833,072 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa right lobe of liver duodenum amniotic fluid kidney metanephros left uterine tube body of pancreas gastric mucosa right lung n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function lipid binding lipase inhibitor activity enzyme regulator activity high-density lipoprotein particle receptor binding cholesterol binding phospholipid binding Cellular component chylomicron very-low-density lipoprotein particle spherical high-density lipoprotein particle extracellular region early endosome extracellular exosome intermediate-density lipoprotein particle extracellular space extracellular matrix collagen-containing extracellular matrix Biological process negative regulation of cholesterol import G protein-coupled receptor signaling pathway negative regulation of very-low-density lipoprotein particle remodeling lipid transport chylomicron remnant clearance negative regulation of fatty acid biosynthetic process regulation of Cdc42 protein signal transduction lipid metabolism negative regulation of high-density lipoprotein particle clearance phospholipid efflux negative regulation of low-density lipoprotein particle clearance negative regulation of very-low-density lipoprotein particle clearance retinoid metabolic process negative regulation of receptor-mediated endocytosis lipid catabolic process cholesterol efflux negative regulation of lipoprotein lipase activity cholesterol homeostasis very-low-density lipoprotein particle assembly negative regulation of triglyceride catabolic process negative regulation of lipid catabolic process negative regulation of lipid metabolic process reverse cholesterol transport triglyceride homeostasis triglyceride metabolic process triglyceride catabolic process chylomicron remodeling high-density lipoprotein particle remodeling chylomicron assembly lipoprotein metabolic process transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 345 n/a Ensembl ENSG00000110245 n/a UniProt P02656 n/a RefSeq (mRNA) NM_000040 n/a RefSeq (protein) NP_000031 n/a Location (UCSC) Chr 11: 116.83 – 116.83 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

Apolipoprotein C-III also known as apo-CIII, and apolipoprotein C3, is a protein that in humans is encoded by the APOC3 gene. Apo-CIII is secreted by the liver as well as the small intestine, and is found on triglyceride-rich lipoproteins such as chylomicrons, very low density lipoprotein (VLDL), and remnant cholesterol.^[3]

Structure

ApoC-III is a relatively small protein containing 79 amino acids that can be glycosylated at threonine-74.^[4] The most abundant glycoforms are characterized by an O-linked disaccharide galactose linked to N-acetylgalactosamine (Gal- GalNAc), further modified with up to 2 sialic acid residues. Less abundant glycoforms are characterized by more complex and fucosylated glycan moieties.^[5]

Function

APOC3 inhibits lipoprotein lipase and hepatic lipase; it is thought to inhibit hepatic uptake^[6] of triglyceride-rich particles. The APOA1, APOC3 and APOA4 genes are closely linked in both rat and human genomes. The A-I and A-IV genes are transcribed from the same strand, while the A-1 and C-III genes are convergently transcribed. An increase in apoC-III levels induces the development of hypertriglyceridemia. Recent evidences suggest an intracellular role for Apo-CIII in promoting the assembly and secretion of triglyceride-rich VLDL particles from hepatic cells under lipid-rich conditions.^[7] However, two naturally occurring point mutations in human apoC3 coding sequence, namely Ala23Thr and Lys58Glu have been shown to abolish the intracellular assembly and secretion of triglyceride-rich VLDL particles from hepatic cells.^[8][9]

Clinical significance

Overexpression of Apo-CIII in humans contributes to atherosclerosis.^[3] Two novel susceptibility haplotypes (specifically, P2-S2-X1 and P1-S2-X1) have been discovered in ApoAI-CIII-AIV gene cluster on chromosome 11q23; these confer approximately threefold higher risk of coronary heart disease in normal^[10] as well as non-insulin diabetes mellitus.^[11] In persons with type 2 diabetes, elevated plasma Apo-CIII is associated with higher plasma triglycerides and greater coronary artery calcification (a measure of subclinical atherosclerosis).^[12]

Apo-CIII delays the catabolism of triglyceride rich particles. HDL cholesterol particles that bear Apo-CIII are associated with increased, rather than decreased, risk for coronary heart disease.^[13]

Elevations of Apo-CIII associated with single-nucleotide polymorphisms found in genetic variation studies may predispose patients to non-alcoholic fatty liver disease,^[14] although the association has been questioned^[15] and may be specific to certain ethnicities^[16][17] or to people without central obesity.^[18]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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|alt=Statin Pathway edit]]

Statin Pathway edit

1. ↑ The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".

Apolipoprotein CIII and HDL

Apolipoprotein CIII is also found on HDL particles. Formation of APOCIII-containing HDL is not a matter of simple binding of APOCII to pre-existing HDL particles but requires the lipid transported ABCA1 in a fashion similar to APOA1-containing HDL.^[19] Accumulation of APOCIII on HDL is important for the maintenance of plasma triglyceride homeostasis since it prevents excessive amount of APOCIII on VLDL and other triglyceride rich lipoproteins, thus preventing APOCIII-mediated inhibition of LpL and the subsequent hydrolysis of plasma triglycerides. This may explain the hypertriglyceridemia associated with ABCA1-deficiency in patients with Tangier's disease.

References

External links

• Apolipoprotein+C-III at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human APOC3 genome location and APOC3 gene details page in the UCSC Genome Browser.

Further reading