PCSK9 Protein, Macaca nemestrina (HEK293, His)

PCSK9 protein plays a crucial role in maintaining the balance of plasma cholesterol levels. It interacts with low-density lipoprotein receptor family members such as LDLR, VLDLR, LRP1/APOER, and LRP8/APOER2, promoting their degradation within acidic compartments of the cell. Through a non-proteolytic mechanism, it enhances the degradation of hepatic LDLR via a clathrin LDLRAP1/ARH-mediated pathway, preventing its recycling from endosomes to the cell surface and directing it to lysosomes for degradation. Additionally, PCSK9 can induce ubiquitination of LDLR, leading to its subsequent degradation. It also inhibits the intracellular degradation of APOB, independent of LDLR, by affecting the autophagosome/lysosome pathway. Moreover, PCSK9 is involved in the early secretory pathway by disposing of non-acetylated intermediates of BACE1. It further regulates epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression, primarily through increased proteasomal degradation. Finally, PCSK9 modulates neuronal apoptosis by regulating the levels of LRP8/APOER2 and related anti-apoptotic signaling pathways.