Apolipoprotein C3

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Apolipoprotein C-III
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols APOC3 ; APOCIII; HALP2
External IDs OMIM107720 MGI88055 HomoloGene81615 GeneCards: APOC3 Gene
RNA expression pattern
PBB GE APOC3 205820 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 345 11814
Ensembl ENSG00000110245 ENSMUSG00000032081
UniProt P02656 P33622
RefSeq (mRNA) NM_000040 NM_023114
RefSeq (protein) NP_000031 NP_075603
Location (UCSC) Chr 11:
116.7 – 116.7 Mb
Chr 9:
46.23 – 46.24 Mb
PubMed search [1] [2]

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).

Structure[edit]

Apo-CIII
Identifiers
Symbol Apo-CIII
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[edit]

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[edit]

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[edit]

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

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

See also[edit]

Apolipoprotein CIII is also on HDL partilcles.

External links[edit]


References[edit]

  1. ^ Vaith P, Assmann G, Uhlenbruck G (June 1978). "Characterization of the oligosaccharide side chain of apolipoprotein C-III from human plasma very low density lipoproteins". Biochim. Biophys. Acta 541 (2): 234–40. doi:10.1016/0304-4165(78)90396-3. PMID 208636. 
  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". J. Proteome Res. 12 (5): 2260–8. doi:10.1021/pr400136p. PMID 23527852. 
  3. ^ 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. 
  4. ^ Sundaram M, Zhong S, Bou Khalil M, Links PH, Zhao Y, Iqbal J, Hussain MM, Parks RJ, Wang Y, Yao Z. (2010). "Expression of apolipoprotein C-III in McA-RH7777 cells enhances VLDL assembly and secretion under lipid-rich conditions.". J Lipid Res. 51 (1): 150–161. doi:10.1194/M900346-JLR200. PMID 19622837. 
  5. ^ Sundaram M, Zhong S, Bou Khalil M, Zhou H, Jiang ZG, Zhao Y, Iqbal J, Hussain MM, Figeys D, Wang Y, Yao Z. (2010). "Functional analysis of the missense APOC3 mutation Ala23Thr associated with human hypotriglyceridemia.". J Lipid Res. 51 (6): 1524–1534. doi:10.1194/jlr.M005108. PMID 20097930. 
  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. (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.". J Biol Chem. 286 (31): 27769–27780. doi:10.1074/jbc.M110.203679. PMID 21676879. 
  7. ^ 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. 
  8. ^ 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. 

Further reading[edit]