APOA4

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

Gene
APOA4 resides on is_associated_with::chromosome 11 in close linkage to is_associated_with::APOA1 and is_associated_with::APOC3. APOA4 contains 3 is_associated_with::exons separated by two is_associated_with::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 is_associated_with::glutamine → is_associated_with::histidine substitution at codon 360 and a is_associated_with::threonine → is_associated_with::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 is_associated_with::intestine; however in mice and rats hepatic synthesis also occurs. Apo A-IV is secreted into circulation on the surface of newly synthesized is_associated_with::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 is_associated_with::lecithin-cholesterol acyltransferase and is_associated_with::cholesterylester transfer protein in vitro;
 * play a role in the regulation of is_associated_with::appetite and is_associated_with::satiety in rodent models;
 * display is_associated_with::anti-oxidant and anti-atherogenic properties in vitro and in rodent models;
 * modulate the efficiency of enterocyte and hepatic transcellular is_associated_with::lipid transport in vitro.

Human apo A-IV deficiency has not been reported.

Interactions
APOA4 has been shown to interact with is_associated_with::GPLD1.