PCSK9

Summary

Gene Symbol: PCSK9
Description: proprotein convertase subtilisin/kexin type 9
Alias: FH3, HCHOLA3, LDLCQ1, NARC-1, NARC1, PC9, proprotein convertase subtilisin/kexin type 9, convertase subtilisin/kexin type 9 preproprotein, neural apoptosis regulated convertase 1, subtilisin/kexin-like protease PC9
Species: human
Products:     PCSK9

Top Publications

  1. Cohen J, Boerwinkle E, Mosley T, Hobbs H. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354:1264-72 pubmed
    ..or absence of sequence variants in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) that are associated with reduced plasma levels of LDL cholesterol. Of the 3363 black subjects examined, 2...
  2. Abifadel M, Varret M, Rabes J, Allard D, Ouguerram K, Devillers M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34:154-6 pubmed
    ..We mapped a third locus associated with ADH, HCHOLA3 at 1p32, and now report two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) ..
  3. Zhang D, Lagace T, Garuti R, Zhao Z, McDonald M, Horton J, et al. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem. 2007;282:18602-12 pubmed
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of hepatic low density lipoprotein receptors (LDLR), the major route of clearance of circulating cholesterol...
  4. Poirier S, Mayer G, Benjannet S, Bergeron E, Marcinkiewicz J, Nassoury N, et al. The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2. J Biol Chem. 2008;283:2363-72 pubmed
    The proprotein convertase PCSK9 gene is the third locus implicated in familial hypercholesterolemia, emphasizing its role in cardiovascular diseases...
  5. McKeown P, Merlini P, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet. 2009;41:334-41 pubmed publisher
    ..observations (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9)...
  6. Mayne J, Dewpura T, Raymond A, Bernier L, Cousins M, Ooi T, et al. Novel loss-of-function PCSK9 variant is associated with low plasma LDL cholesterol in a French-Canadian family and with impaired processing and secretion in cell culture. Clin Chem. 2011;57:1415-23 pubmed publisher
    b>PCSK9 (proprotein convertase subtilisin/kexin type 9) is a polymorphic gene whose protein product regulates plasma LDL cholesterol (LDLC) concentrations by shuttling liver LDL receptors (LDLRs) for degradation...
  7. Sun X, Essalmani R, Day R, Khatib A, Seidah N, Prat A. Proprotein convertase subtilisin/kexin type 9 deficiency reduces melanoma metastasis in liver. Neoplasia. 2012;14:1122-31 pubmed
    ..The proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low-density lipoprotein cholesterol homeostasis by targeting the low-density lipoprotein receptor (LDLR)..
  8. Holla Ø, Strøm T, Cameron J, Berge K, Leren T. A chimeric LDL receptor containing the cytoplasmic domain of the transferrin receptor is degraded by PCSK9. Mol Genet Metab. 2010;99:149-56 pubmed publisher
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the extracellular domain of the low density lipoprotein receptor (LDLR) at the cell surface, and disrupts the normal recycling of the LDLR...
  9. Bingham B, Shen R, Kotnis S, Lo C, Ozenberger B, Ghosh N, et al. Proapoptotic effects of NARC 1 (= PCSK9), the gene encoding a novel serine proteinase. Cytometry A. 2006;69:1123-31 pubmed
    b>NARC 1/PCSK9 encodes a novel serine proteinase known to play a role in cholesterol homeostasis. NARC 1 mRNA expression in cerebellar granule neurons (CGNs) was discovered to be induced following an apoptotic injury...

More Information

Publications128 found, 100 shown here

  1. Poirier S, Mayer G, Poupon V, McPherson P, Desjardins R, Ly K, et al. Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: evidence for an intracellular route. J Biol Chem. 2009;284:28856-64 pubmed publisher
    ..in at least three major genes, the LDL receptor (LDLR), its ligand apolipoprotein B, and the proprotein convertase PCSK9. Single point mutations in PCSK9 are associated with either hyper- or hypocholesterolemia...
  2. Raal F, Panz V, Immelman A, Pilcher G. Elevated PCSK9 levels in untreated patients with heterozygous or homozygous familial hypercholesterolemia and the response to high-dose statin therapy. J Am Heart Assoc. 2013;2:e000028 pubmed publisher
    b>Proprotein convertase subtilisin kexin type 9 (PCSK9) is an enzyme that impairs low-density lipoprotein cholesterol (LDL-C) clearance from the plasma by promoting LDL receptor degradation...
  3. Schmidt R, Beyer T, Bensch W, Qian Y, Lin A, Kowala M, et al. Secreted proprotein convertase subtilisin/kexin type 9 reduces both hepatic and extrahepatic low-density lipoprotein receptors in vivo. Biochem Biophys Res Commun. 2008;370:634-40 pubmed publisher
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is known to reduce hepatic low-density lipoprotein receptor (LDLR) levels and increase plasma LDL cholesterol...
  4. Kotowski I, Pertsemlidis A, Luke A, Cooper R, Vega G, Cohen J, et al. A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol. Am J Hum Genet. 2006;78:410-22 pubmed
    Selected missense mutations in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) cause autosomal dominant hypercholesterolemia, whereas nonsense mutations in the same gene are associated with low plasma ..
  5. Hallman D, Srinivasan S, Chen W, Boerwinkle E, Berenson G. Relation of PCSK9 mutations to serum low-density lipoprotein cholesterol in childhood and adulthood (from The Bogalusa Heart Study). Am J Cardiol. 2007;100:69-72 pubmed
    Specific mutations in the gene for proprotein convertase, subtilisin-kexin type 9 (PCSK9), that are associated with lower coronary heart disease risk may produce lifelong decreases in low-density lipoprotein (LDL) cholesterol levels, but ..
  6. Seidah N, Mayer G, Zaid A, Rousselet E, Nassoury N, Poirier S, et al. The activation and physiological functions of the proprotein convertases. Int J Biochem Cell Biol. 2008;40:1111-25 pubmed publisher
    ..The two other convertases SKI-1/S1P and PCSK9 are implicated in cholesterol and/or fatty acid metabolism...
  7. Mayer G, Poirier S, Seidah N. Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels. J Biol Chem. 2008;283:31791-801 pubmed publisher
    The proprotein convertase subtilisin/kexin-type 9 (PCSK9), which promotes degradation of the hepatic low density lipoprotein receptor (LDLR), is now recognized as a major player in plasma cholesterol metabolism...
  8. Polisecki E, Peter I, Robertson M, McMahon A, Ford I, Packard C, et al. Genetic variation at the PCSK9 locus moderately lowers low-density lipoprotein cholesterol levels, but does not significantly lower vascular disease risk in an elderly population. Atherosclerosis. 2008;200:95-101 pubmed publisher
    Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low-density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (..
  9. Ni Y, Condra J, Orsatti L, Shen X, Di Marco S, Pandit S, et al. A proprotein convertase subtilisin-like/kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake. J Biol Chem. 2010;285:12882-91 pubmed publisher
    b>PCSK9 binds to the low density lipoprotein receptor (LDLR) and leads to LDLR degradation and inhibition of plasma LDL cholesterol clearance...
  10. Humphries S, Whittall R, Hubbart C, Maplebeck S, Cooper J, Soutar A, et al. Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk. J Med Genet. 2006;43:943-9 pubmed
    ..the relative frequency of mutations in three different genes (low-density lipoprotein receptor (LDLR), APOB, PCSK9), and to examine their effect in development of coronary heart disease (CHD) in patients with clinically defined ..
  11. Li S, Guo Y, Xu R, Zhang Y, Zhu C, Sun J, et al. Association of plasma PCSK9 levels with white blood cell count and its subsets in patients with stable coronary artery disease. Atherosclerosis. 2014;234:441-5 pubmed publisher
    Recent studies have suggested that proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with atherosclerosis and plays a potential role in inflammation...
  12. Sun H, Samarghandi A, Zhang N, Yao Z, Xiong M, Teng B. Proprotein convertase subtilisin/kexin type 9 interacts with apolipoprotein B and prevents its intracellular degradation, irrespective of the low-density lipoprotein receptor. Arterioscler Thromb Vasc Biol. 2012;32:1585-95 pubmed publisher
    proprotein convertase subtilisin/kexin type 9 (PCSK9) negatively regulates the low-density lipoprotein (LDL) receptor (LDLR) in hepatocytes and therefore plays an important role in controlling circulating levels of LDL-cholesterol...
  13. Lambert G, Charlton F, Rye K, Piper D. Molecular basis of PCSK9 function. Atherosclerosis. 2009;203:1-7 pubmed publisher
    The LDL receptor (LDLr) inhibitor Proprotein Convertase Subtilisin Kexin type 9 (PCSK9) has emerged as a genetically validated target for lowering plasma LDL cholesterol levels...
  14. Seidah N, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin S, Stifani S, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc Natl Acad Sci U S A. 2003;100:928-33 pubmed
    ..5 telencephalon cells led to enhanced recruitment of undifferentiated neural progenitor cells into the neuronal lineage, suggesting that NARC-1 is implicated in the differentiation of cortical neurons. ..
  15. Holla Ø, Laerdahl J, Strøm T, Tveten K, Cameron J, Berge K, et al. Removal of acidic residues of the prodomain of PCSK9 increases its activity towards the LDL receptor. Biochem Biophys Res Commun. 2011;406:234-8 pubmed publisher
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) at the cell surface and mediates intracellular degradation of the LDLR...
  16. Miyazawa H, Honda T, Miyauchi S, Domon H, Okui T, Nakajima T, et al. Increased serum PCSK9 concentrations are associated with periodontal infection but do not correlate with LDL cholesterol concentration. Clin Chim Acta. 2012;413:154-9 pubmed publisher
    ..Recent studies demonstrated that proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in circulating LDL cholesterol concentrations...
  17. Costet P, Cariou B, Lambert G, Lalanne F, Lardeux B, Jarnoux A, et al. Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c. J Biol Chem. 2006;281:6211-8 pubmed
    ..Mutations in a third gene, proprotein convertase subtilisin kexin 9 (PCSK9), were recently associated to this disease...
  18. Kathiresan S, Melander O, Anevski D, Guiducci C, Burtt N, Roos C, et al. Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med. 2008;358:1240-9 pubmed publisher
    ..The score did not improve risk discrimination but did modestly improve clinical risk reclassification for individual subjects beyond standard clinical factors. ..
  19. Seidah N, Prat A. The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Discov. 2012;11:367-83 pubmed
    ..or paired basic residues, whereas subtilisin kexin isozyme 1 (SKI-1) and proprotein convertase subtilisin kexin 9 (PCSK9) regulate cholesterol and/or lipid homeostasis via cleavage at non-basic residues or through induced degradation ..
  20. Benjannet S, Hamelin J, Chretien M, Seidah N. Loss- and gain-of-function PCSK9 variants: cleavage specificity, dominant negative effects, and low density lipoprotein receptor (LDLR) degradation. J Biol Chem. 2012;287:33745-55 pubmed
    The proprotein convertase PCSK9 is a major target in the treatment of hypercholesterolemia because of its ability bind the LDL receptor (LDLR) and enhance its degradation in endosomes/lysosomes...
  21. Zhang Y, Eigenbrot C, Zhou L, Shia S, Li W, Quan C, et al. Identification of a small peptide that inhibits PCSK9 protein binding to the low density lipoprotein receptor. J Biol Chem. 2014;289:942-55 pubmed publisher
    b>PCSK9 (proprotein convertase subtilisin/kexin type 9) is a negative regulator of the hepatic LDL receptor, and clinical studies with PCSK9-inhibiting antibodies have demonstrated strong LDL-c-lowering effects...
  22. Benjannet S, Rhainds D, Essalmani R, Mayne J, Wickham L, Jin W, et al. NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J Biol Chem. 2004;279:48865-75 pubmed
    The discovery of autosomal dominant hypercholesterolemic patients with mutations in the PCSK9 gene, encoding the proprotein convertase NARC-1, resulting in the missense mutations suggested a role in low density lipoprotein (LDL) ..
  23. McNutt M, Kwon H, Chen C, Chen J, Horton J, Lagace T. Antagonism of secreted PCSK9 increases low density lipoprotein receptor expression in HepG2 cells. J Biol Chem. 2009;284:10561-70 pubmed publisher
    b>PCSK9 is a secreted protein that degrades low density lipoprotein receptors (LDLRs) in liver by binding to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR...
  24. Nassoury N, Blasiole D, Tebon Oler A, Benjannet S, Hamelin J, Poupon V, et al. The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR. Traffic. 2007;8:718-32 pubmed
    Mutations in the proprotein convertase PCSK9 gene are associated with autosomal dominant familial hyper- or hypocholesterolemia...
  25. Taylor A, Wang D, Patel K, Whittall R, Wood G, Farrer M, et al. Mutation detection rate and spectrum in familial hypercholesterolaemia patients in the UK pilot cascade project. Clin Genet. 2010;77:572-80 pubmed publisher
    ..Arg3527Gln and PCSK9 p.Asp374Tyr using a commercial amplification refractory mutation system (ARMS) kit...
  26. Benjannet S, Saavedra Y, Hamelin J, Asselin M, Essalmani R, Pasquato A, et al. Effects of the prosegment and pH on the activity of PCSK9: evidence for additional processing events. J Biol Chem. 2010;285:40965-78 pubmed publisher
    b>PCSK9, a target for the treatment of dyslipidemia, enhances the degradation of the LDL receptor (LDLR) in endosomes/lysosomes, up-regulating LDL-cholesterol levels...
  27. Cariou B, Le Bras M, Langhi C, Le May C, Guyomarc h Delasalle B, Krempf M, et al. Association between plasma PCSK9 and gamma-glutamyl transferase levels in diabetic patients. Atherosclerosis. 2010;211:700-2 pubmed publisher
    b>Proprotein convertase subtilisin kexin type 9 (PCSK9) is a secreted proprotein convertase acting as a natural inhibitor of the low-density lipoprotein (LDL) receptor...
  28. Thompson J, Hyde C, Wood L, Paciga S, Hinds D, Cox D, et al. Comprehensive whole-genome and candidate gene analysis for response to statin therapy in the Treating to New Targets (TNT) cohort. Circ Cardiovasc Genet. 2009;2:173-81 pubmed publisher
    ..Three SNPs in apoE were most highly associated with low-density lipoprotein cholesterol response, followed by 1 in PCSK9 with a similar effect size...
  29. Ding K, Kullo I. Molecular population genetics of PCSK9: a signature of recent positive selection. Pharmacogenet Genomics. 2008;18:169-79 pubmed publisher
    Proprotein convertase subtilisin-like kexin type 9 (PCSK9) is a newly discovered serine protease that plays a key role in regulating plasma low density lipoprotein (LDL) cholesterol levels...
  30. DeVay R, Shelton D, Liang H. Characterization of proprotein convertase subtilisin/kexin type 9 (PCSK9) trafficking reveals a novel lysosomal targeting mechanism via amyloid precursor-like protein 2 (APLP2). J Biol Chem. 2013;288:10805-18 pubmed publisher
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low density lipoprotein receptor protein levels by diverting it to lysosomes...
  31. Dubuc G, Chamberland A, Wassef H, Davignon J, Seidah N, Bernier L, et al. Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2004;24:1454-9 pubmed
    ..The NARC-1 gene, PCSK9, has been identified recently as the third locus implicated in autosomal dominant hypercholesterolemia (ADH)...
  32. Cameron J, Holla Ø, Ranheim T, Kulseth M, Berge K, Leren T. Effect of mutations in the PCSK9 gene on the cell surface LDL receptors. Hum Mol Genet. 2006;15:1551-8 pubmed
    The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is involved in the post-transcriptional regulation of the low-density lipoprotein (LDL) receptors (LDLR)...
  33. Miyake Y, Kimura R, Kokubo Y, Okayama A, Tomoike H, Yamamura T, et al. Genetic variants in PCSK9 in the Japanese population: rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population. Atherosclerosis. 2008;196:29-36 pubmed
    ..lipoprotein cholesterol (LDL-C) levels in the general population are influenced by rare sequence variations in the PCSK9 gene...
  34. Varret M, Abifadel M, Rabes J, Boileau C. Genetic heterogeneity of autosomal dominant hypercholesterolemia. Clin Genet. 2008;73:1-13 pubmed
    ..We have shown further heterogeneity with the discovery of missense mutations in the PCSK9 gene resulting in ADH...
  35. Essalmani R, Susan Resiga D, Chamberland A, Abifadel M, Creemers J, Boileau C, et al. In vivo evidence that furin from hepatocytes inactivates PCSK9. J Biol Chem. 2011;286:4257-63 pubmed publisher
    The proprotein convertase PCSK9 plays a key role in cholesterol homeostasis by binding the LDL receptor and targeting it toward degradation...
  36. Chen S, Ballantyne C, Gotto A, Tan Y, Willerson J, Marian A. A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis. J Am Coll Cardiol. 2005;45:1611-9 pubmed
    We sought to determine the effects of PCSK9 variants on plasma low-density lipoprotein cholesterol (LDL-C) levels, severity of coronary atherosclerosis, and response to statin therapy in the Lipoprotein Coronary Atherosclerosis Study (..
  37. Pisciotta L, Priore Oliva C, Cefalù A, Noto D, Bellocchio A, Fresa R, et al. Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia. Atherosclerosis. 2006;186:433-40 pubmed
    ..coronary disease (pCAD) than simple heterozygotes for mutations in either these genes or for missense mutations in PCSK9 gene. It is not known whether combined mutations in LDLR and PKCS9 are associated with such a severe phenotype...
  38. Folsom A, Peacock J, Boerwinkle E. Variation in PCSK9, low LDL cholesterol, and risk of peripheral arterial disease. Atherosclerosis. 2009;202:211-5 pubmed publisher
    We hypothesized that variants in PCSK9 that lower LDL cholesterol levels are associated with reduced prevalence and incidence of peripheral artery disease (PAD)...
  39. Cariou B, Le May C, Costet P. Clinical aspects of PCSK9. Atherosclerosis. 2011;216:258-65 pubmed publisher
    b>Proprotein convertase subtilisin kexin type 9 (PCSK9) is a circulating protein that impairs LDL clearance by promoting the LDL receptor (LDLR) degradation...
  40. Saavedra Y, Day R, Seidah N. The M2 module of the Cys-His-rich domain (CHRD) of PCSK9 protein is needed for the extracellular low-density lipoprotein receptor (LDLR) degradation pathway. J Biol Chem. 2012;287:43492-501 pubmed publisher
    b>PCSK9 enhances the cellular degradation of the LDL receptor (LDLR), leading to increased plasma LDL cholesterol...
  41. Le Bras M, Roquilly A, Deckert V, Langhi C, Feuillet F, Sébille V, et al. Plasma PCSK9 is a late biomarker of severity in patients with severe trauma injury. J Clin Endocrinol Metab. 2013;98:E732-6 pubmed publisher
    PCSK9 (proprotein convertase subtilisin kexin type 9) is a secreted protease that modulates cholesterol homeostasis by decreasing low-density lipoprotein receptor expression...
  42. Abboud S, Karhunen P, Lutjohann D, Goebeler S, Luoto T, Friedrichs S, et al. Proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is a risk factor of large-vessel atherosclerosis stroke. PLoS ONE. 2007;2:e1043 pubmed
    Genetic variation in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been recently identified as an important determinant of plasma LDL-cholesterol and severity of coronary heart disease...
  43. Le May C, Berger J, Lespine A, Pillot B, Prieur X, Letessier E, et al. Transintestinal cholesterol excretion is an active metabolic process modulated by PCSK9 and statin involving ABCB1. Arterioscler Thromb Vasc Biol. 2013;33:1484-93 pubmed publisher
    ..b>Proprotein convertase subtilisin kexin type 9 (PCSK9)(-/-) mice and intestinal explants show increased LDL-TICE, and acute injection of ..
  44. Kwon H, Lagace T, McNutt M, Horton J, Deisenhofer J. Molecular basis for LDL receptor recognition by PCSK9. Proc Natl Acad Sci U S A. 2008;105:1820-5 pubmed publisher
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) posttranslationally regulates hepatic low-density lipoprotein receptors (LDLRs) by binding to LDLRs on the cell surface, leading to their degradation...
  45. Liu M, Wu G, Baysarowich J, Kavana M, Addona G, Bierilo K, et al. PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain. J Lipid Res. 2010;51:2611-8 pubmed publisher
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that regulates hepatic low-density lipoprotein receptor (LDLR) levels in humans...
  46. Yue P, Averna M, Lin X, Schonfeld G. The c.43_44insCTG variation in PCSK9 is associated with low plasma LDL-cholesterol in a Caucasian population. Hum Mutat. 2006;27:460-6 pubmed
    ..Recently, loss-of-function mutations of PCSK9 gene have been shown to be associated with the hypocholesterolemia phenotype...
  47. McNutt M, Lagace T, Horton J. Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 cells. J Biol Chem. 2007;282:20799-803 pubmed
    Proprotein convertase subtilisin/kexin type 9 (PCSK9), a member of the proteinase K subfamily of subtilases, promotes internalization and degradation of low density lipoprotein receptors (LDLRs) after binding the receptor on the surface ..
  48. Scartezini M, Hubbart C, Whittall R, Cooper J, Neil A, Humphries S. The PCSK9 gene R46L variant is associated with lower plasma lipid levels and cardiovascular risk in healthy U.K. men. Clin Sci (Lond). 2007;113:435-41 pubmed
    In the present study, we have determined the relative frequency of the R46L, I474V and E670G variants in the PCSK9 (protein convertase subtilisin/kexin type 9) gene and its association with plasma lipid levels and CHD (coronary heart ..
  49. Fan D, Yancey P, Qiu S, Ding L, Weeber E, Linton M, et al. Self-association of human PCSK9 correlates with its LDLR-degrading activity. Biochemistry. 2008;47:1631-9 pubmed publisher
    Genetic studies have demonstrated an important role for proprotein convertase subtilisin/kexin type 9 (PCSK9) as a determinant of plasma cholesterol levels. However, the underlying molecular mechanism is not completely understood...
  50. Gupta N, Fisker N, Asselin M, Lindholm M, Rosenbohm C, Ørum H, et al. A locked nucleic acid antisense oligonucleotide (LNA) silences PCSK9 and enhances LDLR expression in vitro and in vivo. PLoS ONE. 2010;5:e10682 pubmed publisher
    The proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important factor in the etiology of familial hypercholesterolemia (FH) and is also an attractive therapeutic target to reduce low density lipoprotein (LDL) cholesterol...
  51. Benn M, Nordestgaard B, Grande P, Schnohr P, Tybjaerg Hansen A. PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta-analyses. J Am Coll Cardiol. 2010;55:2833-42 pubmed publisher
    The aim of this study was to examine the effect of PCSK9 R46L on low-density lipoprotein cholesterol (LDL-C), risk of ischemic heart disease (IHD), and mortality...
  52. Benjannet S, Rhainds D, Hamelin J, Nassoury N, Seidah N. The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications. J Biol Chem. 2006;281:30561-72 pubmed
    b>PCSK9 is the ninth member of the proprotein convertase (PC) family. Some of its natural mutations have been genetically associated with the development of a dominant form of familial hyper- or hypocholesterolemia...
  53. Abifadel M, Rabes J, Boileau C, Varret M. [PCSK9, from gene to protein: a new actor involved in cholesterol homeostasis]. Med Sci (Paris). 2006;22:916-8 pubmed
  54. Kathiresan S. A PCSK9 missense variant associated with a reduced risk of early-onset myocardial infarction. N Engl J Med. 2008;358:2299-300 pubmed publisher
  55. Lakoski S, Lagace T, Cohen J, Horton J, Hobbs H. Genetic and metabolic determinants of plasma PCSK9 levels. J Clin Endocrinol Metab. 2009;94:2537-43 pubmed publisher
    b>PCSK9 is a secreted protein that influences plasma levels of low-density lipoprotein cholesterol (LDL-C) and susceptibility to coronary heart disease...
  56. Wang Y, Huang Y, Hobbs H, Cohen J. Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR. J Lipid Res. 2012;53:1932-43 pubmed publisher
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that promotes degradation of cell surface LDL receptors (LDLRs) in selected cell types...
  57. Zhang D, Garuti R, Tang W, Cohen J, Hobbs H. Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor. Proc Natl Acad Sci U S A. 2008;105:13045-50 pubmed publisher
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that controls plasma LDL cholesterol levels by posttranslational regulation of the LDL receptor (LDLR)...
  58. Huijgen R, Fouchier S, Denoun M, Hutten B, Vissers M, Lambert G, et al. Plasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia. J Lipid Res. 2012;53:979-83 pubmed publisher
    ..that the variability of the FH phenotype might be partly explained by variation in proprotein convertase subtilisin kexin type 9 (PCSK9) activity...
  59. Piper D, Jackson S, Liu Q, Romanow W, Shetterly S, Thibault S, et al. The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol. Structure. 2007;15:545-52 pubmed
    b>Proprotein convertase subtilisin kexin type 9 (PCSK9) has been shown to be involved in the regulation of extracellular levels of the low-density lipoprotien receptor (LDLR)...
  60. Norata G, Garlaschelli K, Grigore L, Raselli S, Tramontana S, Meneghetti F, et al. Effects of PCSK9 variants on common carotid artery intima media thickness and relation to ApoE alleles. Atherosclerosis. 2010;208:177-82 pubmed publisher
    b>PCSK9 plays a key role in plasma cholesterol metabolism by modulating the expression of LDL receptors.
  61. Seidah N, Sadr M, Chretien M, Mbikay M. The multifaceted proprotein convertases: their unique, redundant, complementary, and opposite functions. J Biol Chem. 2013;288:21473-81 pubmed publisher
    ..convertase (PC) family comprises nine members: PC1/3, PC2, furin, PC4, PC5/6, PACE4, PC7, SKI-1/S1P, and PCSK9. The first seven PCs cleave their substrates at single or paired basic residues, and SKI-1/S1P cleaves its ..
  62. Slimani A, Harira Y, Trabelsi I, Jomaa W, Maatouk F, Hamda K, et al. Effect of E670G Polymorphism in PCSK9 Gene on the Risk and Severity of Coronary Heart Disease and Ischemic Stroke in a Tunisian Cohort. J Mol Neurosci. 2014;53:150-7 pubmed publisher
    The association of E670G (rs505151) polymorphism in PCSK9 gene with an increased risk of coronary artery disease (CAD) and ischemic stroke (IS) was reported in previous studies...
  63. Ouguerram K, Chetiveaux M, Zair Y, Costet P, Abifadel M, Varret M, et al. Apolipoprotein B100 metabolism in autosomal-dominant hypercholesterolemia related to mutations in PCSK9. Arterioscler Thromb Vasc Biol. 2004;24:1448-53 pubmed
    ..to mutation in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene previously named neural apoptosis regulated convertase 1 (Narc-1). Our aim was to define the metabolic bases of this new form of hypercholesterolemia...
  64. Allard D, Amsellem S, Abifadel M, Trillard M, Devillers M, Luc G, et al. Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia. Hum Mutat. 2005;26:497 pubmed
    ..We previously demonstrated that ADH is also caused by mutations of the PCSK9 (proprotein convertase subtilisin/kexin type 9) gene that encodes Narc-1 (neural apoptosis-regulated convertase 1)...
  65. Tveten K, Strøm T, Berge K, Leren T. PCSK9-mediated degradation of the LDL receptor generates a 17 kDa C-terminal LDL receptor fragment. J Lipid Res. 2013;54:1560-6 pubmed publisher
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the LDL receptor (LDLR) at the cell surface and reroutes the internalized LDLR to intracellular degradation...
  66. Hooper A, Marais A, Tanyanyiwa D, Burnett J. The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis. 2007;193:445-8 pubmed
    Missense mutations in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) can cause familial hypercholesterolemia...
  67. Seidah N, Prat A. The proprotein convertases are potential targets in the treatment of dyslipidemia. J Mol Med (Berl). 2007;85:685-96 pubmed
    ..furin, PC4, PC5/6, PACE4 and PC7, and two other PCs, SKI-1 (subtilisin-kexin isozyme-1)/S1P (site-1 protease) and PCSK9 (proprotein convertase subtilisin kexin 9) that cleave at nonbasic residues...
  68. Li H, Dong B, Park S, Lee H, Chen W, Liu J. Hepatocyte nuclear factor 1alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine. J Biol Chem. 2009;284:28885-95 pubmed publisher
    b>PCSK9 is a natural inhibitor of LDL receptor (LDLR) that binds the extracellular domain of LDLR and triggers its intracellular degradation...
  69. Arsenault B, Pelletier Beaumont E, Almeras N, Tremblay A, Poirier P, Bergeron J, et al. PCSK9 levels in abdominally obese men: association with cardiometabolic risk profile and effects of a one-year lifestyle modification program. Atherosclerosis. 2014;236:321-6 pubmed publisher
    Studies performed in rodents have suggested a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in insulin resistance and impaired body fat distribution...
  70. Alborn W, Cao G, Careskey H, Qian Y, Subramaniam D, Davies J, et al. Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum LDL cholesterol. Clin Chem. 2007;53:1814-9 pubmed
    b>Proprotein convertase subtilisin kexin type 9 (PCSK9) is gaining attention as a key regulator of serum LDL-cholesterol (LDLC). This novel serine protease causes the degradation of hepatic LDL receptors by an unknown mechanism...
  71. Abifadel M, Rabes J, Jambart S, Halaby G, Gannage Yared M, Sarkis A, et al. The molecular basis of familial hypercholesterolemia in Lebanon: spectrum of LDLR mutations and role of PCSK9 as a modifier gene. Hum Mutat. 2009;30:E682-91 pubmed publisher
    ..in the genes encoding the low-density lipoproteins receptor (LDLR), its ligand apolipoprotein B (APOB) or PCSK9 (Proprotein Convertase Subtilin Kexin 9)...
  72. Browning J, Horton J. Fasting reduces plasma proprotein convertase, subtilisin/kexin type 9 and cholesterol biosynthesis in humans. J Lipid Res. 2010;51:3359-63 pubmed publisher
    Proprotein convertase, subtilisin/kexin type 9 (PCSK9), a key regulator of plasma LDL-cholesterol (LDL-c) and cardiovascular risk, is produced in liver and secreted into plasma where it binds hepatic LDL receptors (LDLR), leading to ..
  73. Jonas M, Costantini C, Puglielli L. PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1. EMBO Rep. 2008;9:916-22 pubmed publisher
    ..Here, we report that the serine protease PCSK9 (proprotein convertase subtilisin kexin type 9) contributes to the disposal of non-acetylated BACE1...
  74. Abifadel M, Rabes J, Devillers M, Munnich A, Erlich D, Junien C, et al. Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease. Hum Mutat. 2009;30:520-9 pubmed publisher
    ..Our discovery in 2003 of the first mutations of the proprotein convertase subtilisin kexin 9 gene (PCSK9) causing ADH shed light on an unknown actor in cholesterol metabolism that since then has been extensively ..
  75. Shioji K, Mannami T, Kokubo Y, Inamoto N, Takagi S, Goto Y, et al. Genetic variants in PCSK9 affect the cholesterol level in Japanese. J Hum Genet. 2004;49:109-14 pubmed
    Mutations in the proprotein convertase subtilisin/kexin 9 ( PCSK9) gene have been reported in affected members of two families with autosomal dominant hypercholesterolemia...
  76. Zhao Z, Tuakli Wosornu Y, Lagace T, Kinch L, Grishin N, Horton J, et al. Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet. 2006;79:514-23 pubmed
    ..Mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) that are associated with lower plasma levels of LDL-C confer protection from coronary heart disease...
  77. Fasano T, Cefalù A, Di Leo E, Noto D, Pollaccia D, Bocchi L, et al. A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol. Arterioscler Thromb Vasc Biol. 2007;27:677-81 pubmed
    The PCSK9 gene, encoding a pro-protein convertase involved in posttranslational degradation of low-density lipoprotein receptor, has emerged as a key regulator of plasma low-density lipoprotein cholesterol...
  78. Cameron J, Holla O, Laerdahl J, Kulseth M, Ranheim T, Rognes T, et al. Characterization of novel mutations in the catalytic domain of the PCSK9 gene. J Intern Med. 2008;263:420-31 pubmed publisher
    To expand our understanding of the structure and function of proprotein convertase subtilisin/kexin type 9 (PCSK9) by studying how naturally occurring mutations in PCSK9 disrupt the function of PCSK9...
  79. Persson L, Henriksson P, Westerlund E, Hovatta O, Angelin B, Rudling M. Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women. Arterioscler Thromb Vasc Biol. 2012;32:810-4 pubmed publisher
    ..Circulating PCSK9, a suppressor of LDL receptors, was reduced 14% when estrogens were high...
  80. Seidah N, Poirier S, Denis M, Parker R, Miao B, Mapelli C, et al. Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation. PLoS ONE. 2012;7:e41865 pubmed publisher
    Proprotein convertase subtilisin/kexin-9 (PCSK9) enhances the degradation of hepatic low-density lipoprotein receptor (LDLR)...
  81. Leren T. Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia. Clin Genet. 2004;65:419-22 pubmed
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is at a locus for autosomal dominant hypercholesterolemia, and recent data indicate that the PCSK9 gene is involved in cholesterol biosynthesis...
  82. Cunningham D, Danley D, Geoghegan K, Griffor M, Hawkins J, Subashi T, et al. Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat Struct Mol Biol. 2007;14:413-9 pubmed
    b>Proprotein convertase subtilisin kexin type 9 (PCSK9) lowers the abundance of surface low-density lipoprotein (LDL) receptor through an undefined mechanism...
  83. Duff C, Scott M, Kirby I, Hutchinson S, Martin S, Hooper N. Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor. Biochem J. 2009;419:577-84 pubmed publisher
    b>PCSK9 (proprotein convertase subtilisin/kexin type 9) promotes degradation of the LDLR [LDL (low-density lipoprotein) receptor] through an as-yet-undefined mechanism, leading to a reduction in cellular LDLc (LDL-cholesterol) and a ..
  84. Holla Ø, Cameron J, Tveten K, Strøm T, Berge K, Laerdahl J, et al. Role of the C-terminal domain of PCSK9 in degradation of the LDL receptors. J Lipid Res. 2011;52:1787-94 pubmed publisher
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) at the cell surface and disrupts the normal recycling of the LDLR...
  85. Lo Surdo P, Bottomley M, Calzetta A, Settembre E, Cirillo A, Pandit S, et al. Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH. EMBO Rep. 2011;12:1300-5 pubmed publisher
    The protein PCSK9 (proprotein convertase subtilisin/kexin type 9) is a key regulator of low-density lipoprotein receptor (LDLR) levels and cardiovascular health...
  86. Timms K, Wagner S, Samuels M, Forbey K, Goldfine H, Jammulapati S, et al. A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree. Hum Genet. 2004;114:349-53 pubmed
    ..This variant results in a D374Y missense change in the gene PCSK9.
  87. Mayer G, Hamelin J, Asselin M, Pasquato A, Marcinkiewicz E, Tang M, et al. The regulated cell surface zymogen activation of the proprotein convertase PC5A directs the processing of its secretory substrates. J Biol Chem. 2008;283:2373-84 pubmed
    ..of PC5A is enhanced, as evidenced by the cleavage of the PC5A substrates Lefty, ADAMTS-4, endothelial lipase, and PCSK9. Our data suggest a novel mechanism for PC5A activation and substrate cleavage at the cell surface, through a ..
  88. Cariou B, Ouguerram K, Zair Y, Guerois R, Langhi C, Kourimate S, et al. PCSK9 dominant negative mutant results in increased LDL catabolic rate and familial hypobetalipoproteinemia. Arterioscler Thromb Vasc Biol. 2009;29:2191-7 pubmed publisher
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a central player in the regulation of cholesterol homeostasis, increasing the low-density lipoprotein (LDL) receptor degradation...
  89. Persson L, Cao G, Stahle L, Sjöberg B, Troutt J, Konrad R, et al. Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans. Arterioscler Thromb Vasc Biol. 2010;30:2666-72 pubmed publisher
    To gain insight into the function of proprotein convertase subtilisin kexin type 9 (PCSK9) in humans by establishing whether circulating levels are influenced by diurnal, dietary, and hormonal changes...
  90. Du F, Hui Y, Zhang M, Linton M, Fazio S, Fan D. Novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. J Biol Chem. 2011;286:43054-61 pubmed publisher
    b>PCSK9 (proprotein convertase subtilisin/kexin type 9) has emerged as a novel therapeutic target for hypercholesterolemia due to its LDL receptor (LDLR)-reducing activity...
  91. Huang C, Fornage M, Lloyd Jones D, Wei G, Boerwinkle E, Liu K. Longitudinal association of PCSK9 sequence variations with low-density lipoprotein cholesterol levels: the Coronary Artery Risk Development in Young Adults Study. Circ Cardiovasc Genet. 2009;2:354-61 pubmed publisher
    Mutations of PCSK9 are associated cross-sectionally with plasma low-density lipoprotein cholesterol (LDL-C) levels, but little is known about their longitudinal association with LDL-C levels from young adulthood to middle age...
  92. Herbert B, Patel D, Waddington S, Eden E, McAleenan A, Sun X, et al. Increased secretion of lipoproteins in transgenic mice expressing human D374Y PCSK9 under physiological genetic control. Arterioscler Thromb Vasc Biol. 2010;30:1333-9 pubmed publisher
    To produce transgenic mice expressing the D374Y variant of the human proprotein convertase subtilisin/kexin type 9 (PCSK9) gene at physiological levels to investigate the mechanisms causing hypercholesterolemia and accelerated ..