Apolipoprotein C3

Apolipoprotein C-III

Identifiers

APOC3; APOCIII; MGC150353

External IDs

OMIM: 107720 MGI: 88055 HomoloGene: 81615 GeneCards: APOC3 Gene

Gene Ontology
Molecular function	• phospholipid binding • cholesterol binding • enzyme regulator activity • lipase inhibitor activity • high-density lipoprotein particle receptor binding
Cellular component	• extracellular region • extracellular region • extracellular space • very-low-density lipoprotein particle • intermediate-density lipoprotein particle • spherical high-density lipoprotein particle • chylomicron
Biological process	• lipid metabolic process • triglyceride metabolic process • triglyceride mobilization • transport • lipid transport • G-protein coupled receptor protein signaling pathway • cholesterol metabolic process • negative regulation of triglyceride catabolic process • negative regulation of very-low-density lipoprotein particle remodeling • negative regulation of very-low-density lipoprotein particle remodeling • negative regulation of very-low-density lipoprotein particle clearance • negative regulation of high-density lipoprotein particle clearance • negative regulation of low-density lipoprotein particle clearance • triglyceride catabolic process • Cdc42 protein signal transduction • cholesterol efflux • phospholipid efflux • high-density lipoprotein particle remodeling • very-low-density lipoprotein particle assembly • chylomicron remnant clearance • lipoprotein metabolic process • cholesterol homeostasis • reverse cholesterol transport • negative regulation of fatty acid biosynthetic process • negative regulation of lipid metabolic process • negative regulation of receptor-mediated endocytosis • negative regulation of lipid catabolic process • negative regulation of lipoprotein lipase activity • negative regulation of cholesterol import • triglyceride homeostasis
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 11:
116.7 – 116.7 Mb

Chr 9:
46.04 – 46.04 Mb

PubMed search

[1]

[2]

Apo-CIII

Identifiers

Symbol

Apo-CIII

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

Apolipoprotein C-III is a protein component of very low density lipoprotein (VLDL). APOC3 inhibits lipoprotein lipase and hepatic lipase; it is thought to inhibit hepatic uptake^[1] 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.

1 Clinical significance
2 Interactive pathway map
3 See also
4 External links
5 References
6 Further reading

Clinical significance

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^[2] as well as non-insulin diabetes mellitus.^[3]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^[4]

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Statin Pathway edit

External links

MeSH Apolipoprotein+C-III

References

^ Mendivil CO, Zheng C, Furtado J, Lel J, Sacks FM (2009). "Metabolism of VLDL and LDL containing apolipoprotein C-III and not other small apolipoproteins – R2". Arteriosclerosis, Thrombosis and Vascular Biology 30 (2): 239–45. doi:10.1161/ATVBAHA.109.197830. PMC 2818784. PMID 19910636. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2818784.
^ Singh PP, Singh M, Kaur TP, Grewal SS (2007). "A novel haplotype in ApoAI-CIII-AIV gene region is detrimental to Northwest Indians with coronary heart disease". Int J Cardiol 130 (3): e93–5. doi:10.1016/j.ijcard.2007.07.029. PMID 17825930.
^ Singh PP, Singh M, Gaur S, Grewal SS (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". Diab Vasc Dis Res 4 (2): 124–29. doi:10.3132/dvdr.2007.030. PMID 17654446.
^ The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430". http://www.wikipathways.org/index.php/Pathway:WP430.

von Eckardstein A, Holz H, Sandkamp M (1991). "Apolipoprotein C-III(Lys58----Glu). Identification of an apolipoprotein C-III variant in a family with hyperalphalipoproteinemia". J. Clin. Invest. 87 (5): 1724–31. doi:10.1172/JCI115190. PMC 295277. PMID 2022742. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=295277.
Karathanasis SK, Zannis VI, Breslow JL (1985). "Isolation and characterization of cDNA clones corresponding to two different human apoC-III alleles". J. Lipid Res. 26 (4): 451–6. PMID 2989400.
Karathanasis SK, Oettgen P, Haddad IA, Antonarakis SE (1986). "Structure, evolution, and polymorphisms of the human apolipoprotein A4 gene (APOA4)". Proc. Natl. Acad. Sci. U.S.A. 83 (22): 8457–61. doi:10.1073/pnas.83.22.8457. PMC 386949. PMID 3095836. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=386949.
Maeda H, Hashimoto RK, Ogura T (1988). "Molecular cloning of a human apoC-III variant: Thr 74—Ala 74 mutation prevents O-glycosylation". J. Lipid Res. 28 (12): 1405–9. PMID 3123586.
Karathanasis SK (1985). "Apolipoprotein multigene family: tandem organization of human apolipoprotein AI, CIII, and AIV genes". Proc. Natl. Acad. Sci. U.S.A. 82 (19): 6374–8. doi:10.1073/pnas.82.19.6374. PMC 390718. PMID 3931073. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=390718.
Zannis VI, Cole FS, Jackson CL (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): 4450–5. doi:10.1021/bi00337a028. PMID 3931677.
Shelley CS, Sharpe CR, Baralle FE, Shoulders CC (1986). "Comparison of the human apolipoprotein genes. Apo AII presents a unique functional intron-exon junction". J. Mol. Biol. 186 (1): 43–51. doi:10.1016/0022-2836(85)90255-4. PMID 3935800.
Hospattankar AV, Brewer HB, Ronan R, Fairwell T (1986). "Amino acid sequence of human plasma apolipoprotein C-III from normolipidemic subjects". FEBS Lett. 197 (1–2): 67–73. doi:10.1016/0014-5793(86)80300-3. PMID 3949020.
Brewer HB, Shulman R, Herbert P (1974). "The complete amino acid sequence of alanine apolipoprotein (apoC-3), and apolipoprotein from human plasma very low density lipoproteins". J. Biol. Chem. 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): 371–3. doi:10.1038/304371a0. PMID 6308458.
Sharpe CR, Sidoli A, Shelley CS (1984). "Human apolipoproteins AI, AII, CII and CIII. cDNA sequences and mRNA abundance". Nucleic Acids Res. 12 (9): 3917–32. doi:10.1093/nar/12.9.3917. PMC 318799. PMID 6328445. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=318799.
Law SW, Gray G, Brewer HB (1983). "cDNA cloning of human apoA-I: amino acid sequence of preproapoA-I". Biochem. Biophys. Res. Commun. 112 (1): 257–64. doi:10.1016/0006-291X(83)91824-7. PMID 6404278.
Protter AA, Levy-Wilson B, Miller J (1985). "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 (1985). "Isolation and DNA sequence of full-length cDNA for human preapolipoprotein CIII". DNA 3 (5): 359–64. doi:10.1089/dna.1984.3.359. PMID 6548954.
Dammerman M, Sandkuijl LA, Halaas JL (1993). "An apolipoprotein CIII haplotype protective against hypertriglyceridemia is specified by promoter and 3' untranslated region polymorphisms". Proc. Natl. Acad. Sci. U.S.A. 90 (10): 4562–6. doi:10.1073/pnas.90.10.4562. PMC 46552. PMID 8099442. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=46552.
Wu JH, Kao JT, Wen MS, Lo SK (2000). "DNA polymorphisms at the apolipoprotein A1-CIII loci in Taiwanese: correlation of plasma APOCIII with triglyceride level and body mass index". J. Formos. Med. Assoc. 99 (5): 367–74. PMID 10870325.
Geraci MW, Moore M, Gesell T (2001). "Gene expression patterns in the lungs of patients with primary pulmonary hypertension: a gene microarray analysis". Circ. Res. 88 (6): 555–62. PMID 11282888.
Inoue Y, Miyazaki M, Tsuji T (2002). "Reactivation of liver-specific gene expression in an immortalized human hepatocyte cell line by introduction of the human HNF4alpha2 gene". Int. J. Mol. Med. 8 (5): 481–7. PMID 11605014.
Pastier D, Lacorte JM, Chambaz J (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". J. Biol. Chem. 277 (17): 15199–206. doi:10.1074/jbc.M200227200. PMID 11839757.
Chhabra S, Narang R, Krishnan LR (Jun 2002). "Apolipoprotein C3 SstI polymorphism and triglyceride levels in Asian Indians". BMC Genet. 3: 9. doi:10.1186/1471-2156-3-9. PMC 116591. PMID 12052247. http://www.biomedcentral.com/1471-2156/3/9.