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- the 3rd letter of the Roman alphabet (同)c
- (music) the keynote of the scale of C major
- a general-purpose programing language closely associated with the UNIX operating system
- the 9th letter of the Roman alphabet (同)i
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- carbonの化学記号
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- iodineの化学記号
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/10/29 11:41:15」(JST)
[Wiki en表示]
| Apolipoprotein C-III |
| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
|
2JQ3
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| Identifiers |
| Symbols |
APOC3; APOCIII; HALP2 |
| 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 space
• early endosome
• very-low-density lipoprotein particle
• intermediate-density lipoprotein particle
• spherical high-density lipoprotein particle
• chylomicron
|
| Biological process |
• retinoid metabolic process
• lipid metabolic process
• triglyceride metabolic process
• triglyceride mobilization
• inflammatory response
• G-protein coupled receptor signaling pathway
• response to nutrient
• phototransduction, visible light
• 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 clearance
• negative regulation of high-density lipoprotein particle clearance
• negative regulation of low-density lipoprotein particle clearance
• triglyceride catabolic process
• regulation of 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
• response to drug
• cholesterol homeostasis
• lipoprotein transport
• response to peptide hormone stimulus
• reverse cholesterol transport
• small molecule metabolic process
• 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
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| Sources: Amigo / QuickGO |
|
| RNA expression pattern |
|
| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
|
| Entrez |
345 |
11814 |
|
| Ensembl |
ENSG00000110245 |
ENSMUSG00000032081 |
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| 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] |
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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
- 1 Structure
- 2 Function
- 3 Clinical significance
- 4 Interactive pathway map
- 5 See also
- 6 External links
- 7 References
- 8 Further reading
Structure[edit]
| Apo-CIII |
| Identifiers |
| Symbol |
Apo-CIII |
| Pfam |
PF05778 |
| InterPro |
IPR008403 |
| Available protein structures: |
| Pfam |
structures |
| PDB |
RCSB PDB; PDBe; PDBj |
| PDBsum |
structure summary |
|
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]
- ^ 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]
- Apolipoprotein C-III at the US National Library of Medicine Medical Subject Headings (MeSH)
References[edit]
- ^ 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. PMID 208636.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
Further reading[edit]
- 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.
- 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.
- 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.
- 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.
- 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. doi:10.1089/dna.1.1984.3.449. 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.
- 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. doi:10.1161/01.RES.88.6.555. 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.
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Lipids: lipoprotein particle metabolism
|
|
| Lipoprotein particle classes and subclasses |
- delivery of TGs: Chylomicron
- VLDL
- delivery of C and CE: IDL
- LDL
- lb LDL
- sd LDL
- Lp(a)
- HDL
|
|
| Apolipoproteins |
- APOA
- APOB
- APOC
- APOD
- APOE
- APOH
|
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| Extracellular enzymes |
|
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| Lipid transfer proteins |
|
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| Cell surface receptors |
- IDL: LRP
- LRP1
- LRP1B
- LRP2
- LRP3
- LRP4
- LRP5
- LRP5L
- LRP6
- LRP8
- LRP10
- LRP11
- LRP12
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| ATP-binding cassette transporter |
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
|
m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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UpToDate Contents
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English Journal
- Amyloid Triangles, Squares, and Loops of Apolipoprotein C-III.
- de Messieres M1, Huang RK, He Y, Lee JC.
- Biochemistry.Biochemistry.2014 May 27;53(20):3261-3. doi: 10.1021/bi500502d. Epub 2014 May 13.
- While a significant component of atherosclerotic plaques has been characterized as amyloid, the specific proteins remain to be fully identified. Probable amyloidogenic proteins are apolipoproteins (Apos), which are vital for the formation and function of lipoproteins. ApoCIII is an abundant protein
- PMID 24804986
- Biological factors in plasma from diabetes mellitus patients enhance hyperglycaemia and pulsatile shear stress-induced endothelial cell apoptosis.
- Liu XF1, Yu JQ, Dalan R, Liu AQ, Luo KQ.
- Integrative biology : quantitative biosciences from nano to macro.Integr Biol (Camb).2014 May;6(5):511-22. doi: 10.1039/c3ib40265g.
- People suffering from Diabetes Mellitus (DM) are prone to an array of vascular complications leading to end organ damage. The hallmark of these vascular complications is endothelium dysfunction, which is caused by endothelial cell (EC) apoptosis. Although the endothelial cell (EC) dysfunction induce
- PMID 24643402
- Genetic score based on high-risk genetic polymorphisms and early onset of ischemic heart disease in an Italian cohort of ischemic patients.
- Vecoli C1, Adlerstein D2, Shehi E3, Bigazzi F4, Sampietro T4, Foffa I5, Carpeggiani C5, L'abbate A6, Andreassi MG7.
- Thrombosis research.Thromb Res.2014 May;133(5):804-10. doi: 10.1016/j.thromres.2014.03.006. Epub 2014 Mar 6.
- Several single-nucleotide polymorphisms (SNPs) have been recognized as associated with ischemic heart disease (IHD) although the optimal set of risk genotypes has not be identified. This study aimed to examine whether identified high-risk SNPs are associated with early onset of IHD. In the GENOCOR s
- PMID 24656450
Japanese Journal
- 先天性皮膚弛緩症と大脳皮質形成異常を伴ったCongenital Disorder of Glycosylation typeIIの1例
- 津田 祐子,舟塚 真,谷 諭美 [他],西川 愛子,伊藤 進,湯浅 勲,大澤 眞木子,TSUDA Yuko,FUNATSUKA Makoto,TANI Yumi,NISHIKAWA Aiko,ITO Susumu,YUASA Isao,OSAWA Makiko
- 東京女子医科大学雑誌 83(E1), E285-E290, 2013-01-31
- … 生後1カ月時にはトランスフェリン等電点電気泳動で異常を認めなかったが、生後6カ月時に再度施行したトランスフェリン、アポリポプロテインC-3等電点電気泳動により異常パターンを呈し、CDG-IIと診断。 …
- NAID 110009559367
- Heritability of Serum Apolipoprotein Concentrations in Middle-Aged Japanese Twins
- CAI Yang Ping,HAYAKAWA Kazuo,NISHIHARA Reiko,KATO Kenji
- Journal of epidemiology 19(5), 260-265, 2009-09-01
- … The aim of this study was to quantify and compare the genetic and environmental causes of individual differences in the serum concentrations of apolipoproteins in Japanese middle-aged twins.<BR>Methods: Apo A-I, apo A-II, apo B, apo C-II, apo C-III, and apo E were studied. …
- NAID 10026250823
- 随時採血で評価できるトリグリセリド代謝マーカーpLPL/apoC-III
- 三宅 紀子,三宅 一徳,日暮 一美 [他],大坂 顯通
- 臨床病理 = THE OFFICIAL JOURNAL OF JAPANESE SOCIETY OF LABORATORY MEDICINE 55(11), 1019-1024, 2007-11-25
- NAID 10021234542
Related Links
- 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 of triglyceride-rich particles. The APOA1, APOC3 and APOA4 genes ...
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- 関
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