APOA4

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.{{cite journal |vauthors=Luo CC, Li WH, Moore MN, Chan L | title = Structure and evolution of the apolipoprotein multigene family | journal = J. Mol. Biol. | volume = 187 | issue = 3 | pages = 325–340 |date=February 1986 | pmid = 3084795 | doi = 10.1016/0022-2836(86)90436-5}}

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.{{cite web | title = Entrez Gene: APOA4 apolipoprotein A-IV| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=337}}

Human apo A-IV deficiency has not been reported.

APOA4 has been shown to interact with GPLD1.{{cite journal |last=Deeg |first=M A |author2=Bierman E L |author3=Cheung M C |date=March 2001 |title=GPI-specific phospholipase D associates with an apoA-I- and apoA-IV-containing complex |journal=J. Lipid Res. |volume=42 |issue=3 |pages=442–51 |location = United States|doi=10.1016/S0022-2275(20)31669-2 | issn = 0022-2275| pmid = 11254757 |doi-access=free }}

{{StatinPathway_WP430|highlight=APOA4}}

{{Reflist}}

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• {{cite journal |vauthors=Elshourbagy NA, Walker DW, Boguski MS |title=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. |journal=J. Biol. Chem. |volume=261 |issue= 5 |pages= 1998–2002 |year= 1986 |doi=10.1016/S0021-9258(17)35888-X |pmid= 3080432 |display-authors=etal|doi-access=free }}
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• {{cite journal |vauthors=Menzel HJ, Dieplinger H, Sandholzer C |title=Apolipoprotein A-IV polymorphism in the Hungarian population: gene frequencies, effect on lipid levels, and sequence of two new variants. |journal=Hum. Mutat. |volume=5 |issue= 1 |pages= 58–65 |year= 1995 |pmid= 7728150 |doi= 10.1002/humu.1380050108 |s2cid=3063305 |display-authors=etal|doi-access=free }}
• {{cite journal |vauthors=Duverger N, Tremp G, Caillaud JM |title=Protection against atherogenesis in mice mediated by human apolipoprotein A-IV |journal=Science |volume=273 |issue= 5277 |pages= 966–8 |year= 1996 |pmid= 8688083 |doi=10.1126/science.273.5277.966 |display-authors=etal|bibcode=1996Sci...273..966D |s2cid=30484255 }}
• {{cite journal |vauthors=Deeb SS, Nevin DN, Iwasaki L, Brunzell JD |title=Two novel apolipoprotein A-IV variants in individuals with familial combined hyperlipidemia and diminished levels of lipoprotein lipase activity. |journal=Hum. Mutat. |volume=8 |issue= 4 |pages= 319–25 |year= 1997 |pmid= 8956036 |doi= 10.1002/(SICI)1098-1004(1996)8:4<319::AID-HUMU4>3.0.CO;2-2 |s2cid=19100488 }}

{{Refend}}

• {{MeshName|Apolipoprotein+A-IV}}
• {{UCSC gene info|APOA4}}

{{Lipoproteins}}

{{DEFAULTSORT:Apoa4}}

Category:Apolipoproteins

{{Gene-11-stub}}