Recombinant Human Apolipoprotein A-V (APOA5), partial

Function

Minor apolipoprotein mainly associated with HDL and to a lesser extent with VLDL. May also be associated with chylomicrons. Important determinant of plasma triglyceride (TG) levels by both being a potent stimulator of apo-CII lipoprotein lipase (LPL) TG hydrolysis and an inhibitor of the hepatic VLDL-TG production rate (without affecting the VLDL-apoB production rate) (By similarity). Activates poorly lecithin:cholesterol acyltransferase (LCAT) and does not enhance efflux of cholesterol from macrophages. Binds heparin (PubMed:17326667)

Subcellular Location

Secreted; Early endosome; Late endosome; Golgi apparatus, trans-Golgi network

Disease Association

Hypertriglyceridemia 1 (HYTG1) : A common inherited disorder in which the concentration of very low density lipoprotein (VLDL) is elevated in the plasma. This leads to increased risk of heart disease, obesity, and pancreatitis. Inheritance is autosomal dominant. [Disease susceptibility is associated with variants affecting the gene represented in this entry] | Hyperlipoproteinemia 5 (HLPP5) : Characterized by increased amounts of chylomicrons and very low density lipoprotein (VLDL) and decreased low density lipoprotein (LDL) and high density lipoprotein (HDL) in the plasma after a fast. Numerous conditions cause this phenotype, including insulin-dependent diabetes mellitus, contraceptive steroids, alcohol abuse, and glycogen storage disease type 1A (GSD1A). [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Liver and plasma

Subunit

Interacts with GPIHBP1 (PubMed:17997385). Interacts with SORL1; this interaction leads to APOA5 internalization and sorting either to lysosomes and degradation, or to the trans-Golgi network (PubMed:17326667, PubMed:18603531)

• van Der Vliet H.N. et al. Apolipoprotein A-V. A novel apolipoprotein associated with an early phase of liver regeneration. — J. Biol. Chem. (2001)
• Fullerton S.M. et al. The effects of scale: variation in the APOA1/C3/A4/A5 gene cluster. — Hum. Genet. (2004)
• Clark H.F. et al. The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. — Genome Res. (2003)
• PubMed: CI-FDNV3U1C1I228 (FEB-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Pennacchio L.A. et al. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. — Science (2001)
• Beckstead J.A. et al. Structure-function studies of human apolipoprotein A-V: a regulator of plasma lipid homeostasis. — Biochemistry (2003)
• Prieur X. et al. The human apolipoprotein AV gene is regulated by peroxisome proliferator-activated receptor-alpha and contains a novel farnesoid X-activated receptor response element. — J. Biol. Chem. (2003)