ANGPTL3

Angiopoietin-like 3, also known as ANGPTL3, is a is_associated_with::protein that in humans is encoded by the ANGPTL3 is_associated_with::gene.

Function
The protein encoded by this gene is a member of the is_associated_with::angiopoietin-like family of secreted factors. It is expressed predominantly in the liver, and has the characteristic structure of angiopoietins, consisting of a is_associated_with::signal peptide, N-terminal is_associated_with::coiled-coil domain, and the C-terminal is_associated_with::fibrinogen (FBN)-like domain. The FBN-like domain in angiopoietin-like 3 protein was shown to bind alpha-5/beta-3 integrins, and this binding induced endothelial is_associated_with::cell adhesion and migration. This protein may also play a role in the regulation of is_associated_with::angiogenesis.

Angptl3 also acts as dual inhibitor of is_associated_with::lipoprotein lipase (LPL) and is_associated_with::endothelial lipase (EL), and increases plasma triglyceride and HDL cholesterol in rodents. ANGPTL3 inhibit endothelial lipase to catalyze HDL-phospholipid and increase HDL-PL levels. Circulating PL-rich HDL particles have high cholesterol efflux abilities.

Clinical significance
In human, ANGPTL3 is a determinant factor of HDL level and positively correlates with plasma HDL cholesterol.

In humans with genetic loss-of-function variants in one copy of ANGPTL3, the serum LDL-C levels are reduced. In those with loss-of-function variants in both copies of ANGPTL3, low LDL-C, low HDL-C, and low triglycerides are seen ("is_associated_with::familial combined hypolipidemia").