PCSK9 Cell Lysate – Tissue Lysate

This gene encodes a proprotein convertase belonging to the proteinase K subfamily of the secretory subtilase family. The encoded protein is synthesized as a soluble zymogen that undergoes autocatalytic intramolecular processing in the endoplasmic reticulum. The protein may function as a proprotein convertase. This protein plays a role in cholesterol homeostasis and may have a role in the differentiation of cortical neurons. Mutations in this gene have been associated with a third form of autosomal dominant familial hypercholesterolemia (HCHOLA3). [provided by RefSeq, Jul 2008]

PCSK9: Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways. Defects in PCSK9 are the cause of hypercholesterolemia autosomal dominant type 3 (HCHOLA3). A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins. Belongs to the peptidase S8 family. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: EC 3.4.21.-; Secreted; Protease; Secreted, signal peptide; Cell development/differentiation

Chromosomal Location of Human Ortholog: 1p32.3

Cellular Component: Golgi apparatus; extracellular space; cell surface; extrinsic to external side of plasma membrane; rough endoplasmic reticulum; endoplasmic reticulum; lysosome; perinuclear region of cytoplasm; early endosome; cytoplasm; late endosome; plasma membrane; ER to Golgi transport vesicle

Molecular Function: sodium channel inhibitor activity; very-low-density lipoprotein binding; protein binding; protein self-association; low-density lipoprotein receptor binding; serine-type endopeptidase activity; low-density lipoprotein binding; apolipoprotein binding; apolipoprotein receptor binding

Biological Process: cholesterol metabolic process; lysosomal transport; apoptosis; positive regulation of receptor internalization; lipoprotein metabolic process; regulation of low-density lipoprotein receptor catabolic process; proteolysis; liver development; cellular response to starvation; neuron differentiation; protein autoprocessing; cholesterol homeostasis; triacylglycerol metabolic process; cellular response to insulin stimulus; neurogenesis; phospholipid metabolic process; positive regulation of neuron apoptosis; regulation of neuron apoptosis; negative regulation of receptor recycling; low-density lipoprotein receptor catabolic process; regulation of receptor activity; kidney development

Disease: Hypercholesterolemia, Autosomal Dominant, 3