PCSK9

PCSK9
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2P4E, 2PMW, 2QTW, 2W2M, 2W2N, 2W2O, 2W2P, 2W2Q, 2XTJ, 3BPS, 3GCW, 3GCX, 3H42, 3M0C, 3P5B, 3P5C, 3SQO, 4K8R, 4NE9, 4NMX, 4OV6
Identifiers
Aliases	PCSK9, proprotein convertase subtilisin/kexin type 9, FH3, HCHOLA3, LDLCQ1, NARC-1, NARC1, PC9, FHCL3
External IDs	OMIM: 607786 MGI: 2140260 HomoloGene: 17790 GeneCards: PCSK9
Gene location (Human)
Chr.	Chromosome 1 (human)
End	55,064,852 bp
Gene location (Mouse)
Chr.	Chromosome 4 (mouse)
End	106,321,526 bp
RNA expression pattern
	Top expressed in
	right lobe of liver; ; cerebellar hemisphere; ; secondary oocyte; ; upper lobe of left lung; ; right lung; ; body of pancreas; ; islet of Langerhans; ; duodenum; ; lower lobe of lung; ; ganglionic eminence;
	Top expressed in
	renal calyx; ; midgut; ; Hindgut; ; liver; ; Paneth cell; ; anal canal; ; ileum; ; lobe of liver; ; left lobe of liver; ; left colon;
	More reference expression data
	n/a
Gene ontology
Molecular function	apolipoprotein binding; apolipoprotein receptor binding; very-low-density lipoprotein particle binding; low-density lipoprotein particle binding; protein self-association; sodium channel inhibitor activity; low-density lipoprotein particle receptor binding; very-low-density lipoprotein particle receptor binding; peptidase activity; protein binding; serine-type peptidase activity; signaling receptor inhibitor activity; serine-type endopeptidase activity; hydrolase activity; RNA binding;
Cellular component	cytoplasm; endosome; late endosome; rough endoplasmic reticulum; Golgi apparatus; plasma membrane; PCSK9-AnxA2 complex; cell surface; early endosome; extrinsic component of external side of plasma membrane; endoplasmic reticulum; perinuclear region of cytoplasm; COPII-coated ER to Golgi transport vesicle; lysosome; PCSK9-LDLR complex; extracellular region; extracellular space; lysosomal membrane; endolysosome membrane; endoplasmic reticulum lumen;
Biological process	lipoprotein metabolic process; neurogenesis; steroid metabolic process; kidney development; positive regulation of receptor internalization; lipid metabolism; negative regulation of low-density lipoprotein particle clearance; negative regulation of sodium ion transmembrane transporter activity; regulation of low-density lipoprotein particle receptor catabolic process; cellular response to starvation; regulation of neuron apoptotic process; protein processing; regulation of signaling receptor activity; cholesterol metabolic process; protein autoprocessing; proteolysis; positive regulation of neuron apoptotic process; positive regulation of low-density lipoprotein particle receptor catabolic process; low-density lipoprotein receptor particle metabolic process; neuron differentiation; cellular response to insulin stimulus; lysosomal transport; phospholipid metabolic process; liver development; cholesterol homeostasis; triglyceride metabolic process; negative regulation of receptor recycling; apoptotic process; negative regulation of low-density lipoprotein particle receptor binding; negative regulation of low-density lipoprotein receptor activity; negative regulation of receptor-mediated endocytosis involved in cholesterol transport; low-density lipoprotein particle receptor catabolic process; low-density lipoprotein particle clearance; post-translational protein modification; negative regulation of signaling receptor activity;
	Sources:Amigo / QuickGO
Orthologs
	255738
	100102
	ENSG00000169174
	ENSMUSG00000044254
	Q8NBP7
	Q80W65
	NM_174936
	NM_153565
	NP_777596
	NP_705793
	Wikidata
View/Edit Human	View/Edit Mouse

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the PCSK9 gene in humans on chromosome 1. It is the 9th member of the proprotein convertase family of proteins that activate other proteins. Similar genes (orthologs) are found across many species. As with many proteins, PCSK9 is inactive when first synthesized, because a section of peptide chains blocks their activity; proprotein convertases remove that section to activate the enzyme. The PCSK9 gene also contains one of 27 loci associated with increased risk of coronary artery disease.

PCSK9 is ubiquitously expressed in many tissues and cell types. PCSK9 binds to and degrades the receptor for low-density lipoprotein particles (LDL), which typically transport 3,000 to 6,000 fat molecules (including cholesterol) per particle, within extracellular fluid. The LDL receptor (LDLR), on liver and other cell membranes, binds and initiates ingestion of LDL-particles from extracellular fluid into cells and targets the complex to lysosomes for destruction. If PCSK9 is blocked, the LDL-LDLR complex separates during trafficking, with the LDL digested in the lysosome, but the LDLRs instead recycled back to the cell surface and so able to remove additional LDL-particles from the extracellular fluid. Therefore, blocking PCSK9 can lower blood LDL-particle concentrations.

PCSK9 has medical importance because it acts in lipoprotein homeostasis. Agents that block PCSK9 can lower LDL particle concentrations. The first two PCSK9 inhibitors, alirocumab and evolocumab, were approved as once every two week injections, by the U.S. Food and Drug Administration in 2015 for lowering LDL-particle concentrations when statins and other drugs were not sufficiently effective or poorly tolerated. The cost of these new medications, as of 2015, was $14,000 per year at full retail; judged of unclear cost effectiveness by some. While these medications are prescribed by many physicians, the payment for prescriptions are often denied by insurance providers. As a result, pharmaceutical manufacturers lowered the prices of these drugs.

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