Apolipoprotein C3

Apolipoprotein C-III also known as apo-CIII is a is_associated_with::protein that in humans is encoded by the APOC3 is_associated_with::gene. Apo-CIII is a component of is_associated_with::very low density lipoprotein (VLDL).

Structure
ApoCIII is a relatively small protein containing 79 amino acids that can be is_associated_with::glycosylated at is_associated_with::threonine-74. The most abundant glycoforms are characterized by an O-linked disaccharide galactose linked to is_associated_with::N-acetylgalactosamine (Gal- GalNAc), further modified with up to 2 is_associated_with::sialic acid residues. Less abundant glycoforms are characterized by more complex and fucosylated is_associated_with::glycan moieties.

Function
APOC3 inhibits is_associated_with::lipoprotein lipase and is_associated_with::hepatic lipase; it is thought to inhibit hepatic uptake of is_associated_with::triglyceride-rich particles. The is_associated_with::APOA1, APOC3 and is_associated_with::APOA4 genes are closely linked in both rat and human is_associated_with::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 is_associated_with::hypertriglyceridemia. Recent evidences suggest an intracellular role for Apo-CIII in promoting the assembly and secretion of triglyceride-rich VLDL particles from hepatic cells under lipid-rich conditions. However, two naturally occurring point mutations in human apoC3 coding sequence, namely Ala23Thr and Lys58Glu have been shown to abolish the intracellular assembly and secretion of triglyceride-rich VLDL particles from hepatic cells.

Clinical significance
Two novel susceptibility is_associated_with::haplotypes (specifically, P2-S2-X1 and P1-S2-X1) have been discovered in ApoAI-CIII-AIV is_associated_with::gene cluster on is_associated_with::chromosome 11q23; these confer approximately threefold higher risk of is_associated_with::coronary heart disease in normal as well as non-insulin is_associated_with::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.