Angiopoietin-like 3, Recombinant, Human (ANGPTL3, ANGPT5)

ANGPTL3 is a secreted glycoprotein that is structurally related to the angiopoietins. Mature human ANGPTL3 contains an N-terminal coiled coil domain and a C-terminal fibrinogen-like domain. ANGPTL3 is expressed in the liver from early in development through adulthood. Full length ANGPTL3 circulates in the plasma as do proteolytically separated N- and C-terminal fragments containing the coiled coil domain and fibrinogen-like domains. ANGPTL3 is found as 70kD, 50kD, and 32kD species. ANGPTL3 directly inhibits lipoprotein lipase (LPL) and endothelial lipase (EL), enzymes responsible for hydrolyzing circulating triglycerides and HDL phospholipids. This activity requires a putative heparin-binding motif which is N-terminal to the coiled coil domain. Proteolytic removal of the fibrinogen-like domain from the N-terminal fragment serves to activate ANGPTL3 and increase its ability to inhibit LPL in vitro and function in vivo. ANGPTL3 promotes an increase in circulating triglyceride levels without altering VLDL or HDL secretion or uptake. ANGPTL3 knockout mice are hypolipidemic and have elevated LPL activity. ANGPTL3 expression in vivo is upregulated by LXR agonists and downregulated by insulin, leptin, and agonists of TRb or PPARb. Dysregulated ANGPTL3 expression and elevated plasma triglyceride levels are characteristic of some strains of obese and diabetic mice. ANGPTL3 does not bind Tie1 or Tie2, but its fibrinogen-like domain interacts with integrin aVb3 to induce endothelial cell adhesion, migration, and neovascularization. ANGPTL3, secreted by fetal liver, also promotes the expansion of hematopoietic stem cells. Mature human ANGPTL3 shares 24%-30% aa sequence identity with ANGPTL1, 2, 4, 5, 6, and 7. It shares 77% aa sequence identity with mouse ANGPTL3. A DNA sequence encoding human Angiopoietin-like 3 (Met 1-Glu 460, Accession # Q9Y5C1) was fused to a 10X histidine tag at the C-terminus. The protein was expressed in Sf 21 cells. , Calculated molecular mass of 53.2kD. The recombinant protein migrates at ~ 54-59kD in SDS-PAGE under reducing conditions. Activity: Measured by its ability to inhibit lipoprotein lipase activity. , Endotoxin: <1EU/ug. Storage and Stability: Lyophilized powder may be stored at 4°C for short-term only. Reconstitute to nominal volume by adding sterile PBS and store at -20°C. Reconstituted product is stable for 12 months at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.