PCSK9

From Wikipedia, the free encyclopedia


Proprotein convertase subtilisin/kexin type 9
PDB rendering based on 2p4e.
Available structures: 2p4e, 2pmw
Identifiers
Symbol(s) PCSK9; FH3; HCHOLA3; NARC-1; NARC1
External IDs OMIM: 607786 MGI: 2140260 HomoloGene: 17790
Orthologs
Human Mouse
Entrez 255738 100102
Ensembl ENSG00000169174 ENSMUSG00000044254
Uniprot Q8NBP7 Q5PYH4
Refseq NM_174936 (mRNA)
NP_777596 (protein)		 NM_153565 (mRNA)
NP_705793 (protein)
Location Chr 1: 55.28 - 55.3 Mb Chr 4: 105.94 - 105.96 Mb
Pubmed search [1] [2]

Proprotein convertase subtilisin/kexin type 9, also known as PCSK9, is a human gene with orthologs found across many species.

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).[1]

[edit] References

  1. ^ Entrez Gene: PCSK9 proprotein convertase subtilisin/kexin type 9.

[edit] Further reading

  • Abifadel M, Rabès JP, Boileau C, Varret M (2007). "[After the LDL receptor and apolipoprotein B, autosomal dominant hypercholesterolemia reveals its third protagonist: PCSK9]". Ann. Endocrinol. (Paris) 68 (2-3): 138–46. doi:10.1016/j.ando.2007.02.002. PMID 17391637. 
  • Lambert G (2007). "Unravelling the functional significance of PCSK9.". Curr. Opin. Lipidol. 18 (3): 304–9. doi:10.1097/MOL.0b013e3281338531. PMID 17495605. 
  • Varret M, Rabès JP, Saint-Jore B, et al. (1999). "A third major locus for autosomal dominant hypercholesterolemia maps to 1p34.1-p32.". Am. J. Hum. Genet. 64 (5): 1378–87. PMID 10205269. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932. 
  • Seidah NG, Benjannet S, Wickham L, et al. (2003). "The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation.". Proc. Natl. Acad. Sci. U.S.A. 100 (3): 928–33. doi:10.1073/pnas.0335507100. PMID 12552133. 
  • Abifadel M, Varret M, Rabès JP, et al. (2003). "Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.". Nat. Genet. 34 (2): 154–6. doi:10.1038/ng1161. PMID 12730697. 
  • Naureckiene S, Ma L, Sreekumar K, et al. (2004). "Functional characterization of Narc 1, a novel proteinase related to proteinase K.". Arch. Biochem. Biophys. 420 (1): 55–67. PMID 14622975. 
  • Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
  • Timms KM, Wagner S, Samuels ME, et al. (2004). "A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree.". Hum. Genet. 114 (4): 349–53. doi:10.1007/s00439-003-1071-9. PMID 14727179. 
  • Leren TP (2004). "Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia.". Clin. Genet. 65 (5): 419–22. doi:10.1111/j.0009-9163.2004.0238.x. PMID 15099351. 
  • Ouguerram K, Chetiveaux M, Zair Y, et al. (2005). "Apolipoprotein B100 metabolism in autosomal-dominant hypercholesterolemia related to mutations in PCSK9.". Arterioscler. Thromb. Vasc. Biol. 24 (8): 1448–53. doi:10.1161/01.ATV.0000133684.77013.88. PMID 15166014. 
  • Dubuc G, Chamberland A, Wassef H, et al. (2005). "Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia.". Arterioscler. Thromb. Vasc. Biol. 24 (8): 1454–9. doi:10.1161/01.ATV.0000134621.14315.43. PMID 15178557. 
  • Benjannet S, Rhainds D, Essalmani R, et al. (2005). "NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol.". J. Biol. Chem. 279 (47): 48865–75. doi:10.1074/jbc.M409699200. PMID 15358785. 
  • Cohen J, Pertsemlidis A, Kotowski IK, et al. (2005). "Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9.". Nat. Genet. 37 (2): 161–5. doi:10.1038/ng1509. PMID 15654334. 
  • Lalanne F, Lambert G, Amar MJ, et al. (2005). "Wild-type PCSK9 inhibits LDL clearance but does not affect apoB-containing lipoprotein production in mouse and cultured cells.". J. Lipid Res. 46 (6): 1312–9. doi:10.1194/jlr.M400396-JLR200. PMID 15741654. 
  • Sun XM, Eden ER, Tosi I, et al. (2005). "Evidence for effect of mutant PCSK9 on apolipoprotein B secretion as the cause of unusually severe dominant hypercholesterolaemia.". Hum. Mol. Genet. 14 (9): 1161–9. doi:10.1093/hmg/ddi128. PMID 15772090. 
  • Pisciotta L, Priore Oliva C, Cefalù AB, et al. (2006). "Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia.". Atherosclerosis 186 (2): 433–40. doi:10.1016/j.atherosclerosis.2005.08.015. PMID 16183066. 
  • Allard D, Amsellem S, Abifadel M, et al. (2006). "Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia.". Hum. Mutat. 26 (5): 497. doi:10.1002/humu.9383. PMID 16211558. 
  • Naoumova RP, Tosi I, Patel D, et al. (2006). "Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: long-term follow-up and treatment response.". Arterioscler. Thromb. Vasc. Biol. 25 (12): 2654–60. doi:10.1161/01.ATV.0000190668.94752.ab. PMID 16224054. 
  • Shibata N, Ohnuma T, Higashi S, et al. (2006). "No genetic association between PCSK9 polymorphisms and Alzheimer's disease and plasma cholesterol level in Japanese patients.". Psychiatr. Genet. 15 (4): 239. PMID 16314752. 
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