Contents

Apolipoprotein C-III

Protein-coding gene in the species Homo sapiens

APOC3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2JQ3
Identifiers
Aliases	APOC3, APOCIII, HALP2, apolipoprotein C3, Apo-C3, ApoC-3
External IDs	OMIM: 107720; MGI: 88055; HomoloGene: 81615; GeneCards: APOC3; OMA:APOC3 - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q23.3 Start 116,829,706 bp[1] End 116,833,072 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 A5.2|9 25.36 cM Start 46,144,231 bp[2] End 46,146,934 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa right lobe of liver mucosa of ileum duodenum gonad amniotic fluid human kidney epithelium of colon metanephros left uterine tube Top expressed in left lobe of liver duodenum jejunum migratory enteric neural crest cell yolk sac ileum right kidney proximal tubule median eminence intestinal epithelium 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 11814 Ensembl ENSG00000110245 ENSMUSG00000032081 UniProt P02656 P33622 RefSeq (mRNA) NM_000040 NM_023114 NM_001289755 NM_001289756 NM_001289833 RefSeq (protein) NP_000031 NP_001276684 NP_001276685 NP_001276762 NP_075603 Location (UCSC) Chr 11: 116.83 – 116.83 Mb Chr 9: 46.14 – 46.15 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[5]

Structure[edit]

ApoC-III is a relatively small protein containing 79 amino acids that can be glycosylatedatthreonine-74.^[6] The most abundant glycoforms are characterized by an O-linked disaccharide galactose linked to N-acetylgalactosamine (Gal–GalNAc), further modified with up to two sialic acid residues. Less abundant glycoforms are characterized by more complex and fucosylated glycan moieties.^[7]

Function[edit]

APOC3 inhibits lipoprotein lipase and hepatic lipase; it is thought to inhibit hepatic uptake^[8]oftriglyceride-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.^[9] 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.^[10][11]

Clinical significance[edit]

Overexpression of Apo-CIII in humans contributes to atherosclerosis.^[5] Two novel susceptibility haplotypes (specifically, P2-S2-X1 and P1-S2-X1) have been discovered in ApoAI-CIII-AIV gene clusteronchromosome 11q23; these confer approximately threefold higher risk of coronary heart disease in normal^[12] as well as non-insulin diabetes mellitus.^[13] 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).^[14]

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.^[15]

Elevations of Apo-CIII associated with single-nucleotide polymorphisms found in genetic variation studies may predispose patients to non-alcoholic fatty liver disease,^[16] although the association has been questioned^[17] and may be specific to certain ethnicities^[18][19] or to people without central obesity.^[20]

Antisense oligonucleotides that bind APOC3 mRNA and prevent its translation have been found to reduce episodes of acute pancreatitis in people with familial chylomicronemia syndrome and lower their triglyceride levels in blood. Adverse effects include thrombocytopenia, which may be prevented by targeting hepatocellular APOC3 expression with a chemically modified oligonucleotide.^[21]

Interactive pathway map[edit]

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

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Apolipoprotein CIII and HDL[edit]

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.^[22] 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[edit]

^ Singh P, Singh M, Gaur S, Kaur T (Jun 2007). "The ApoAI-CIII-AIV gene cluster and its relation to lipid levels in type 2 diabetes mellitus and coronary heart disease: determination of a novel susceptible haplotype". Diabetes & Vascular Disease Research. 4 (2): 124–29. doi:10.3132/dvdr.2007.030. PMID 17654446. S2CID 23793589.

External links[edit]

• 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[edit]