Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Antibody – Rabbit Polyclonal

This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an autocatalytic processing event with its prosegment in the ER and is constitutively secreted as an inactive protease into the extracellular matrix and trans-Golgi network. It is expressed in liver, intestine and kidney tissues and escorts specific receptors for lysosomal degradation. It plays a role in cholesterol and fatty acid metabolism. Mutations in this gene have been associated with autosomal dominant familial hypercholesterolemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

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

Chromosomal Location of Human Ortholog: 1p32.3

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

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

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

Disease: Hypercholesterolemia, Autosomal Dominant, 3