Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)

FH3; HCHOLA3; NARC1; Hypercholesterolemia,Autosomal Dominant 3; Neural apoptosis-regulated convertase 1; Proprotein convertase 9; Subtilisin/kexin-like protease PC9

SPN	S596
HGNC	20001
MGI	2140260
PubMed	18666258
RGD	728909
UniProt	Q8NBP7
Wiki	PCSK9

PCSK9 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 major regulatory role in cholesterol homeostasis. PCSK9 binds to the epidermal growth factor-like repeat A (EGF-A) domain of the low-density lipoprotein receptor (LDLR), inducing LDLR degradation. Reduced LDLR levels result in decreased metabolism of low-density lipoproteins, which could lead to hypercholesterolemia. Inhibition of PSCK9 function is currently being explored as a means of lowering cholesterol levels. PCSK9 may also have a role in the differentiation of cortical neurons.

Reference

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Patent number WO0131007, 03-MAY-2001

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PLoS ONE 2:E1098-E1098(2007) [PubMed] [Europe PMC] [Abstract]

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Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

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Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]

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Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]

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"Self-association of human PCSK9 correlates with its LDLR-degrading activity."
Biochemistry 47:1631-1639(2008) [PubMed] [Europe PMC] [Abstract]

"PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1."
EMBO Rep. 9:916-922(2008) [PubMed] [Europe PMC] [Abstract]

"PCSK9 is phosphorylated by a Golgi casein kinase-like kinase ex vivo and circulates as a phosphoprotein in humans."
FEBS J. 275:3480-3493(2008) [PubMed] [Europe PMC] [Abstract]

"The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2."
J. Biol. Chem. 283:2363-2372(2008) [PubMed] [Europe PMC] [Abstract]

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Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

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"Novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein."
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"Proprotein convertase subtilisin/kexin type 9 interacts with apolipoprotein B and prevents its intracellular degradation, irrespective of the low-density lipoprotein receptor."
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"Molecular basis of PCSK9 function."
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"PCSK9: a convertase that coordinates LDL catabolism."
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"Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease."
Hum. Mutat. 30:520-529(2009) [PubMed] [Europe PMC] [Abstract]

"Effect of mutations in LDLR and PCSK9 genes on phenotypic variability in Tunisian familial hypercholesterolemia patients."
Atherosclerosis 222:158-166(2012) [PubMed] [Europe PMC] [Abstract]

"Regulation of epithelial sodium channel trafficking by proprotein convertase subtilisin/kexin type 9 (PCSK9)."
J. Biol. Chem. 287:19266-19274(2012) [PubMed] [Europe PMC] [Abstract]

"The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol."
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"Mutations in PCSK9 cause autosomal dominant hypercholesterolemia."
Nat. Genet. 34:154-156(2003) [PubMed] [Europe PMC] [Abstract]

"A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol."
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"The molecular basis of familial hypercholesterolemia in Lebanon: spectrum of LDLR mutations and role of PCSK9 as a modifier gene."
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"Genetic variation in APOB, PCSK9, and ANGPTL3 in carriers of pathogenic autosomal dominant hypercholesterolemic mutations with unexpected low LDL-Cl Levels."
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