Summary: Apolipoprotein CIII (Apo-CIII)
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Apolipoprotein C3 Edit Wikipedia article
|RNA expression pattern|
ApoCIII is a relatively small protein containing 79 amino acids that can be glycosylated at threonine-74. 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.
APOC3 inhibits lipoprotein lipase and hepatic lipase; it is thought to inhibit hepatic uptake 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.
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 as well as non-insulin diabetes mellitus.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]
- The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".
Apolipoprotein CIII is also on HDL partilcles.
- 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.
- 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.
- 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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Apolipoprotein CIII (Apo-CIII) Provide feedback
This family consists of several mammalian apolipoprotein CIII (Apo-CIII) sequences. Apolipoprotein C-III is a 79-residue glycoprotein. It is synthesised in the intestine and liver as part of the very low density lipoprotein (VLDL) and the high density lipoprotein (HDL) particles. Owing to its positive correlation with plasma triglyceride (Tg) levels, Apo-CIII is suggested to play a role in Tg metabolism and is therefore of interest regarding atherosclerosis. However, unlike other apolipoproteins such as Apo-AI, Apo E or CII for which many naturally occurring mutations are known, the structure-function relationships of apo C-III remains a subject of debate. One possibility is that apo C-III inhibits lipoprotein lipase (LPL) activity, as shown by in vitro experiments. Another suggestion, is that elevated levels of Apo-CIII displace other apolipoproteins at the lipoprotein surface, modifying their clearance from plasma .
Lins L, Flore C, Chapelle L, Talmud PJ, Thomas A, Brasseur R; , Protein Eng 2002;15:513-520.: Lipid-interacting properties of the N-terminal domain of human apolipoprotein C-III. PUBMED:12082170 EPMC:12082170
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR008403This family consists of several mammalian apolipoprotein CIII (Apo-CIII) sequences. Apolipoprotein C-III is a 79-residue glycoprotein. It is synthesised in the intestine and liver as part of the very low density lipoprotein (VLDL) and the high density lipoprotein (HDL) particles. Owing to its positive correlation with plasma triglyceride (Tg) levels, Apo-CIII is suggested to play a role in Tg metabolism and is therefore of interest regarding atherosclerosis. However, unlike other apolipoproteins such as Apo-AI, Apo E or CII for which many naturally occurring mutations are known, the structure-function relationships of apo C-III remains a subject of debate. One possibility is that apo C-III inhibits lipoprotein lipase (LPL) activity, as shown by in vitro experiments. Another suggestion, is that elevated levels of Apo-CIII displace other apolipoproteins at the lipoprotein surface, modifying their clearance from plasma [PUBMED:12082170].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||extracellular region (GO:0005576)|
|Molecular function||lipid binding (GO:0008289)|
|Biological process||lipid transport (GO:0006869)|
|lipoprotein metabolic process (GO:0042157)|
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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|Seed source:||Pfam-B_7283 (release 8.0)|
|Number in seed:||6|
|Number in full:||42|
|Average length of the domain:||65.00 aa|
|Average identity of full alignment:||61 %|
|Average coverage of the sequence by the domain:||62.42 %|
|HMM build commands:||
build method: hmmbuild --amino -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||7|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
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Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Apo-CIII domain has been found. There are 1 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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