Apolipoprotein C-III

APOC3
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

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

Structure

ApoC-III
Identifiers
Symbol	ApoC-III
Pfam	PF05778
InterPro	IPR008403
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

ApoC-III is a relatively small protein containing 79 amino acids that can be

Function

APOC3 inhibits

. 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

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

Interactive pathway map

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

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

• von Eckardstein A, Holz H, Sandkamp M, Weng W, Funke H, Assmann G (May 1991). "Apolipoprotein C-III(Lys58----Glu). Identification of an apolipoprotein C-III variant in a family with hyperalphalipoproteinemia". The Journal of Clinical Investigation. 87 (5): 1724–31.
  PMID 2022742
  .
• Karathanasis SK, Zannis VI, Breslow JL (Apr 1985). "Isolation and characterization of cDNA clones corresponding to two different human apoC-III alleles". Journal of Lipid Research. 26 (4): 451–56.
  PMID 2989400
  .
• Karathanasis SK, Oettgen P, Haddad IA, Antonarakis SE (Nov 1986). "Structure, evolution, and polymorphisms of the human apolipoprotein A4 gene (APOA4)". Proceedings of the National Academy of Sciences of the United States of America. 83 (22): 8457–61.
  PMID 3095836
  .
• Maeda H, Hashimoto RK, Ogura T, Hiraga S, Uzawa H (Dec 1987). "Molecular cloning of a human apoC-III variant: Thr 74----Ala 74 mutation prevents O-glycosylation". Journal of Lipid Research. 28 (12): 1405–09.
  PMID 3123586
  .
• Karathanasis SK (Oct 1985). "Apolipoprotein multigene family: tandem organization of human apolipoprotein AI, CIII, and AIV genes". Proceedings of the National Academy of Sciences of the United States of America. 82 (19): 6374–78.
  PMID 3931073
  .
• Zannis VI, Cole FS, Jackson CL, Kurnit DM, Karathanasis SK (Jul 1985). "Distribution of apolipoprotein A-I, C-II, C-III, and E mRNA in fetal human tissues. Time-dependent induction of apolipoprotein E mRNA by cultures of human monocyte-macrophages". Biochemistry. 24 (16): 4450–55.
  PMID 3931677
  .
• Shelley CS, Sharpe CR, Baralle FE, Shoulders CC (Nov 1985). "Comparison of the human apolipoprotein genes. Apo AII presents a unique functional intron-exon junction". Journal of Molecular Biology. 186 (1): 43–51.
  PMID 3935800
  .
• Hospattankar AV, Brewer HB, Ronan R, Fairwell T (Mar 1986). "Amino acid sequence of human plasma apolipoprotein C-III from normolipidemic subjects". FEBS Letters. 197 (1–2): 67–73.
  S2CID 83923614
  .
• Brewer HB, Shulman R, Herbert P, Ronan R, Wehrly K (Aug 1974). "The complete amino acid sequence of alanine apolipoprotein (apoC-3), and apolipoprotein from human plasma very low density lipoproteins". The Journal of Biological Chemistry. 249 (15): 4975–84.
  PMID 4846755
  .
• Karathanasis SK, McPherson J, Zannis VI, Breslow JL (1983). "Linkage of human apolipoproteins A-I and C-III genes". Nature. 304 (5924): 371–73.
  S2CID 4336695
  .
• Sharpe CR, Sidoli A, Shelley CS, Lucero MA, Shoulders CC, Baralle FE (May 1984). "Human apolipoproteins AI, AII, CII and CIII. cDNA sequences and mRNA abundance". Nucleic Acids Research. 12 (9): 3917–32.
  PMID 6328445
  .
• Law SW, Gray G, Brewer HB (Apr 1983). "cDNA cloning of human apoA-I: amino acid sequence of preproapoA-I". Biochemical and Biophysical Research Communications. 112 (1): 257–64.
  PMID 6404278
  .
• Protter AA, Levy-Wilson B, Miller J, Bencen G, White T, Seilhamer JJ (Dec 1984). "Isolation and sequence analysis of the human apolipoprotein CIII gene and the intergenic region between the apo AI and apo CIII genes". DNA. 3 (6): 449–56.
  PMID 6439535
  .
• Levy-Wilson B, Appleby V, Protter A, Auperin D, Seilhamer JJ (Oct 1984). "Isolation and DNA sequence of full-length cDNA for human preapolipoprotein CIII". DNA. 3 (5): 359–64.
  PMID 6548954
  .
• Dammerman M, Sandkuijl LA, Halaas JL, Chung W, Breslow JL (May 1993). "An apolipoprotein CIII haplotype protective against hypertriglyceridemia is specified by promoter and 3' untranslated region polymorphisms". Proceedings of the National Academy of Sciences of the United States of America. 90 (10): 4562–66.
  PMID 8099442
  .
• Wu JH, Kao JT, Wen MS, Lo SK (May 2000). "DNA polymorphisms at the apolipoprotein A1-CIII loci in Taiwanese: correlation of plasma APOCIII with triglyceride level and body mass index". Journal of the Formosan Medical Association = Taiwan Yi Zhi. 99 (5): 367–74.
  PMID 10870325
  .
• Geraci MW, Moore M, Gesell T, Yeager ME, Alger L, Golpon H, Gao B, Loyd JE, Tuder RM, Voelkel NF (Mar 2001). "Gene expression patterns in the lungs of patients with primary pulmonary hypertension: a gene microarray analysis". Circulation Research. 88 (6): 555–62.
  PMID 11282888
  .
• Inoue Y, Miyazaki M, Tsuji T, Sakaguchi M, Fukaya K, Huh NH, Namba M (Nov 2001). "Reactivation of liver-specific gene expression in an immortalized human hepatocyte cell line by introduction of the human HNF4alpha2 gene". International Journal of Molecular Medicine. 8 (5): 481–87.
  PMID 11605014
  .
• Pastier D, Lacorte JM, Chambaz J, Cardot P, Ribeiro A (Apr 2002). "Two initiator-like elements are required for the combined activation of the human apolipoprotein C-III promoter by upstream stimulatory factor and hepatic nuclear factor-4". The Journal of Biological Chemistry. 277 (17): 15199–206.
  PMID 11839757
  .
• Chhabra S, Narang R, Krishnan LR, Vasisht S, Agarwal DP, Srivastava LM, Manchanda SC, Das N (Jun 2002). "Apolipoprotein C3 SstI polymorphism and triglyceride levels in Asian Indians". BMC Genetics. 3: 9.
  PMID 12052247
  .