APOA4

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a
Wikidata
View/Edit Human

Apolipoprotein A-IV (also known as apoA-IV, apoAIV, or apoA4) is plasma protein that is the product of the human gene APOA4.

Gene

APOA4 resides on chromosome 11 in close linkage to APOA1 and APOC3. APOA4 contains 3 exons separated by two introns, and is polymorphic, although most of the reported sequence polymorphisms occur in exon 3. The best validated and studied non-synonymous SNPs are a glutamine → histidine substitution at codon 360 and a threonine → serine substitution at codon 347; a sequence polymorphism has also been identified in the 3'UTR of the third exon. Intra-species comparative gene sequence analysis suggests that the APOA4 gene arose from APOA1 by gene duplication approximately 270 MYA.

Function

The primary translation product of the APOA4 gene is a 396-residue preprotein, which undergoes proteolytic processing to yield apo A-IV, a 376-residue mature O-linked glycoprotein. In most mammals, including humans, apo A-IV synthesis is confined to the intestine; however in mice and rats hepatic synthesis also occurs. Apo A-IV is secreted into circulation on the surface of newly synthesized chylomicron particles. Intestinal fat absorption dramatically increases the synthesis and secretion of apo A-IV. Although its primary function in human lipid metabolism has not been established, apo A-IV has been found to:

• activate lecithin-cholesterol acyltransferase and cholesterylester transfer protein in vitro;
• play a role in the regulation of appetite and satiety in rodent models;
• display anti-oxidant and anti-atherogenic properties in vitro and in rodent models;
• modulate the efficiency of enterocyte and hepatic transcellular lipid transport in vitro.

Human apo A-IV deficiency has not been reported.

Interactions

APOA4 has been shown to interact with GPLD1.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.

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Statin Pathway edit

Further reading

• von Eckardstein A, Funke H, Schulte M, et al. (1992). "Nonsynonymous polymorphic sites in the apolipoprotein (apo) A-IV gene are associated with changes in the concentration of apo B- and apo A-I-containing lipoproteins in a normal population". American Journal of Human Genetics. 50 (5): 1115–28. PMC 1682587. PMID 1349197.
• Kamboh MI, Williams ER, Law JC, et al. (1993). "Molecular basis of a unique African variant (A-IV 5) of human apolipoprotein A-IV and its significance in lipid metabolism". Genet. Epidemiol. 9 (6): 379–88. doi:10.1002/gepi.1370090602. PMID 1487136.
• Lohse P, Kindt MR, Rader DJ, Brewer HB (1991). "Three genetic variants of human plasma apolipoprotein A-IV. apoA-IV-1(Thr347----Ser), apoA-IV-0(Lys167----Glu,Gln360----His), and apoA-IV-3(Glu165----Lys)". J. Biol. Chem. 266 (21): 13513–8. PMID 1677358.
• Tenkanen H, Koskinen P, Metso J, et al. (1992). "A novel polymorphism of apolipoprotein A-IV is the result of an asparagine to serine substitution at residue 127". Biochim. Biophys. Acta. 1138 (1): 27–33. doi:10.1016/0925-4439(92)90147-f. PMID 1737067.
• Lohse P, Kindt MR, Rader DJ, Brewer HB (1990). "Human plasma apolipoproteins A-IV-0 and A-IV-3. Molecular basis for two rare variants of apolipoprotein A-IV-1". J. Biol. Chem. 265 (21): 12734–9. PMID 1973689.
• Tenkanen H, Lukka M, Jauhiainen M, et al. (1991). "The mutation causing the common apolipoprotein A-IV polymorphism is a glutamine to histidine substitution of amino acid 360". Arterioscler. Thromb. 11 (4): 851–6. doi:10.1161/01.atv.11.4.851. PMID 2065039.
• de Temmerman P, Visvikis S, Boerwinkle E, Siest G (1990). "Study of the sequence tagged site (STS) in the beginning of human apo A4 gene region". Nucleic Acids Res. 18 (18): 5576. doi:10.1093/nar/18.18.5576. PMC 332267. PMID 2216752.
• Wei S, Rocchi M, Archidiacono N, et al. (1990). "Physical mapping of the human chromosome 11q23 region containing the ataxia-telangiectasia locus". Cancer Genet. Cytogenet. 46 (1): 1–8. doi:10.1016/0165-4608(90)90002-R. PMID 2331673.
• Lohse P, Kindt MR, Rader DJ, Brewer HB (1990). "Genetic polymorphism of human plasma apolipoprotein A-IV is due to nucleotide substitutions in the apolipoprotein A-IV gene". J. Biol. Chem. 265 (17): 10061–4. PMID 2351649.
• Yang CY, Gu ZW, Chong IS, et al. (1989). "The primary structure of human apolipoprotein A-IV". Biochim. Biophys. Acta. 1002 (2): 231–7. doi:10.1016/0005-2760(89)90292-0. PMID 2930771.
• Elshourbagy NA, Walker DW, Boguski MS, et al. (1986). "The nucleotide and derived amino acid sequence of human apolipoprotein A-IV mRNA and the close linkage of its gene to the genes of apolipoproteins A-I and C-III". J. Biol. Chem. 261 (5): 1998–2002. PMID 3080432.
• Bisgaier CL, Sachdev OP, Lee ES, et al. (1987). "Effect of lecithin:cholesterol acyltransferase on distribution of apolipoprotein A-IV among lipoproteins of human plasma". J. Lipid Res. 28 (6): 693–703. PMID 3611972.
• Karathanasis SK, Yunis I, Zannis VI (1986). "Structure, evolution, and tissue-specific synthesis of human apolipoprotein AIV". Biochemistry. 25 (13): 3962–70. doi:10.1021/bi00361a034. PMID 3755616.
• Karathanasis SK (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. Bibcode:1985PNAS...82.6374K. doi:10.1073/pnas.82.19.6374. PMC 390718. PMID 3931073.
• Gordon JI, Bisgaier CL, Sims HF, et al. (1984). "Biosynthesis of human preapolipoprotein A-IV". J. Biol. Chem. 259 (1): 468–74. PMID 6706947.
• Menzel HJ, Dieplinger H, Sandholzer C, et al. (1995). "Apolipoprotein A-IV polymorphism in the Hungarian population: gene frequencies, effect on lipid levels, and sequence of two new variants". Hum. Mutat. 5 (1): 58–65. doi:10.1002/humu.1380050108. PMID 7728150.
• Duverger N, Tremp G, Caillaud JM, et al. (1996). "Protection against atherogenesis in mice mediated by human apolipoprotein A-IV". Science. 273 (5277): 966–8. Bibcode:1996Sci...273..966D. doi:10.1126/science.273.5277.966. PMID 8688083.
• Deeb SS, Nevin DN, Iwasaki L, Brunzell JD (1997). "Two novel apolipoprotein A-IV variants in individuals with familial combined hyperlipidemia and diminished levels of lipoprotein lipase activity". Hum. Mutat. 8 (4): 319–25. doi:10.1002/(SICI)1098-1004(1996)8:4<319::AID-HUMU4>3.0.CO;2-2. PMID 8956036.

External links

• Apolipoprotein+A-IV at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human APOA4 genome location and APOA4 gene details page in the UCSC Genome Browser.