Apolipoprotein C3

Apolipoprotein C3

Apolipoprotein C-III
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; APOCIII; HALP2
External IDs GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Apolipoprotein C-III also known as apo-CIII is a protein that in humans is encoded by the APOC3 gene. Apo-CIII is a component of very low density lipoprotein (VLDL).

Contents

  • Structure 1
  • Function 2
  • Clinical significance 3
  • Interactive pathway map 4
  • See also 5
  • References 6
  • External links 7
  • Further reading 8

Structure

ApoC-III
Identifiers
Symbol ApoC-III
Pfam PF05778
InterPro IPR008403

ApoCIII is a relatively small protein containing 79 amino acids that can be glycosylated at threonine-74.[1] 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.[2]

Function

APOC3 inhibits lipoprotein lipase and hepatic lipase; it is thought to inhibit hepatic uptake[3] 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.[4] 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.[5][6]

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[7] as well as non-insulin diabetes mellitus.[8] Apo-CIII delays the catabolism of triglyceride rich particles. Elevations of Apo-CIII found in genetic variation studies may predispose patients to non-alcoholic fatty liver disease.

Interactive pathway map

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

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Statin Pathway edit
  1. ^ The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430". 

See also

Apolipoprotein CIII is also on HDL partilcles.

References

  1. ^ Vaith P, Assmann G, Uhlenbruck G (Jun 1978). "Characterization of the oligosaccharide side chain of apolipoprotein C-III from human plasma very low density lipoproteins". Biochimica et Biophysica Acta 541 (2): 234–40.  
  2. ^ Nicolardi S, van der Burgt YE, Dragan I, Hensbergen PJ, Deelder AM (May 2013). "Identification of new apolipoprotein-CIII glycoforms with ultrahigh resolution MALDI-FTICR mass spectrometry of human sera". Journal of Proteome Research 12 (5): 2260–8.  
  3. ^ Mendivil CO, Zheng C, Furtado J, Lel J, Sacks FM (Feb 2010). "Metabolism of very-low-density lipoprotein and low-density lipoprotein containing apolipoprotein C-III and not other small apolipoproteins". Arteriosclerosis, Thrombosis, and Vascular Biology 30 (2): 239–45.  
  4. ^ Sundaram M, Zhong S, Bou Khalil M, Links PH, Zhao Y, Iqbal J, Hussain MM, Parks RJ, Wang Y, Yao Z (Jan 2010). "Expression of apolipoprotein C-III in McA-RH7777 cells enhances VLDL assembly and secretion under lipid-rich conditions". Journal of Lipid Research 51 (1): 150–161.  
  5. ^ Sundaram M, Zhong S, Bou Khalil M, Zhou H, Jiang ZG, Zhao Y, Iqbal J, Hussain MM, Figeys D, Wang Y, Yao Z (Jun 2010). "Functional analysis of the missense APOC3 mutation Ala23Thr associated with human hypotriglyceridemia". Journal of Lipid Research 51 (6): 1524–1534.  
  6. ^ Qin W, Sundaram M, Wang Y, Zhou H, Zhong S, Chang CC, Manhas S, Yao EF, Parks RJ, McFie PJ, Stone SJ, Jiang ZG, Wang C, Figeys D, Jia W, Yao Z (Aug 2011). "Missense mutation in APOC3 within the C-terminal lipid binding domain of human ApoC-III results in impaired assembly and secretion of triacylglycerol-rich very low density lipoproteins: evidence that ApoC-III plays a major role in the formation of lipid precursors within the microsomal lumen". The Journal of Biological Chemistry 286 (31): 27769–27780.  
  7. ^ Singh P, Singh M, Kaur TP, Grewal SS (Nov 2008). "A novel haplotype in ApoAI-CIII-AIV gene region is detrimental to Northwest Indians with coronary heart disease". International Journal of Cardiology 130 (3): e93–5.  
  8. ^ 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.  

External links

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.  
  • 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): 451–6.  
  • 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.  
  • 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): 1405–9.  
  • 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): 6374–8.  
  • 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): 4450–5.  
  • 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.  
  • 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.  
  • 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.  
  • Karathanasis SK, McPherson J, Zannis VI, Breslow JL (1983). "Linkage of human apolipoproteins A-I and C-III genes". Nature 304 (5924): 371–3.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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): 4562–6.  
  • 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.  
  • 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.  
  • 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): 481–7.  
  • 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.  
  • 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.