Biotin anti-mouse PCSK9 Antibody anti-PCSK9 - Poly5251,BioLegend,525104

Proprotein convertase subtilisin/kexin 9 (PCSK9) possesses a signal peptide, a prosegment, a catalytic domain, a hinge region, and a C-terminal Cys-His-rich domain. This protein is primarily synthesized and secreted by hepatocytes. Besides the liver, it is also expressed in the small intestine, kidney, and brain. It is also present in plasma. Upon translocation to the endoplasmic reticulum, the prosegment of PCSK9 is autocatalytically cleaved and secreted as a stable, enzymatically inactive, non-covalent complex. Elevated low density lipoprotein-cholesterol (LDLc) level is a major risk factor for cardiovascular disease and atherosclerosis. PCSK9 is a regulator of LDLc levels through the binding of LDLR, which subsequently leads to the degradation of LDLR. PCSK9 null mice fed with a high fat diet demonstrated a four-fold decrease in cholesterol accumulation, which stresses the important role played by PCSK9 in the development of cardiovascular diseases. PCSK9 also binds to other LDLR family members such as very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER), and apolipoprotein receptor 2 (LRP8/APOER2), which leads to their degradation in intracellular acidic compartments. Like the LDLR, gene expression of PCSK9 is positively regulated by sterol regulatory element-binding protein 2 (SREBP-2), which is a transcription factor that is activated in response to cellular cholesterol depletion.