Pcsk2

Summary

Gene Symbol: Pcsk2
Description: proprotein convertase subtilisin/kexin type 2
Alias: neuroendocrine convertase 2, KEX2-like endoprotease 2, NEC 2, PC2, prohormone convertase 2, proprotein convertase 2
Species: rat
Products:     Pcsk2

Top Publications

  1. Taylor N, Shennan K, Cutler D, Docherty K. Mutations within the propeptide, the primary cleavage site or the catalytic site, or deletion of C-terminal sequences, prevents secretion of proPC2 from transfected COS-7 cells. Biochem J. 1997;321 ( Pt 2):367-73 pubmed
    b>PC2 is a neuroendocrine endoprotease involved in the processing of prohormones and proneuropeptides. PC2 is synthesized as a proenzyme which undergoes proteolytic maturation within the cellular secretory apparatus...
  2. Perello M, Friedman T, Paez Espinosa V, Shen X, Stuart R, Nillni E. Thyroid hormones selectively regulate the posttranslational processing of prothyrotropin-releasing hormone in the paraventricular nucleus of the hypothalamus. Endocrinology. 2006;147:2705-16 pubmed
    ..with parallel changes in the levels of two members of the family of prohormone convertases 1/3 and 2 (PC1/3 and PC2)...
  3. Mousa S, Shakibaei M, Sitte N, Schafer M, Stein C. Subcellular pathways of beta-endorphin synthesis, processing, and release from immunocytes in inflammatory pain. Endocrinology. 2004;145:1331-41 pubmed
    ..present study was to examine the presence of POMC, carboxypeptidase E, the prohormone convertases 1 (PC1), and 2 (PC2), PC2-binding protein 7B2, and the release of END from inflammatory cells in rats...
  4. Davidson H, Rhodes C, Hutton J. Intraorganellar calcium and pH control proinsulin cleavage in the pancreatic beta cell via two distinct site-specific endopeptidases. Nature. 1988;333:93-6 pubmed
  5. Miller R, Aaron W, Toneff T, Vishnuvardhan D, Beinfeld M, Hook V. Obliteration of alpha-melanocyte-stimulating hormone derived from POMC in pituitary and brains of PC2-deficient mice. J Neurochem. 2003;86:556-63 pubmed
    ..Therefore, this study investigated the in vivo role of the prohormone convertase 2 (PC2) processing enzyme for production of alpha-MSH in PC2-deficient mice...
  6. Takahashi T, Ida T, Sato T, Nakashima Y, Nakamura Y, Tsuji A, et al. Production of n-octanoyl-modified ghrelin in cultured cells requires prohormone processing protease and ghrelin O-acyltransferase, as well as n-octanoic acid. J Biochem. 2009;146:675-82 pubmed publisher
    ..We found that not only PC1/3 but also both PC2 and furin could process proghrelin to the 28-amino acid ghrelin...
  7. Billova S, Galanopoulou A, Seidah N, Qiu X, Kumar U. Immunohistochemical expression and colocalization of somatostatin, carboxypeptidase-E and prohormone convertases 1 and 2 in rat brain. Neuroscience. 2007;147:403-18 pubmed
    ..Several previous studies have predicted that carboxypeptidase-E (CPE), prohormone convertase 1 (PC1) and prohormone convertase 2 (PC2) may function as sorting elements for somatostatin (SST) for its maturation and processing to ..
  8. Zheng M, Streck R, Scott R, Seidah N, Pintar J. The developmental expression in rat of proteases furin, PC1, PC2, and carboxypeptidase E: implications for early maturation of proteolytic processing capacity. J Neurosci. 1994;14:4656-73 pubmed
    The genes encoding mammalian subtilisin-like endoproteases furin, PC1, and PC2 have been isolated and are implicated in endoproteolytic cleavage of precursor molecules, which is a key step in posttranslational maturation of proproteins ..
  9. Tang S, Zhang J, Liu H, Li H. PC2/CPE-mediated pro-protein processing in tumor cells and its differentiated cells or tissues. Mol Cell Endocrinol. 2009;303:43-9 pubmed publisher
    Pro-protein convertase-2 (PC2) and carboxypeptidase-E (CPE) proteins are two major members of the pro-protein convertases that involve in the maturation of protein precursor...

Scientific Experts

More Information

Publications37

  1. Paulsson J, Westermark G. Aberrant processing of human proislet amyloid polypeptide results in increased amyloid formation. Diabetes. 2005;54:2117-25 pubmed
    ..This step is performed by the prohormone convertases PC2 and PC1/3...
  2. Poirier S, Prat A, Marcinkiewicz E, Paquin J, Chitramuthu B, Baranowski D, et al. Implication of the proprotein convertase NARC-1/PCSK9 in the development of the nervous system. J Neurochem. 2006;98:838-50 pubmed
    ..convertases subtilisin kexin isozyme 1/site 1 protease and Furin was unaffected by RA, whereas that of PC5/6 and PC2 increased within and/or after the first 4 days of the differentiation period respectively...
  3. DeBoer M, Zhu X, Levasseur P, Inui A, Hu Z, Han G, et al. Ghrelin treatment of chronic kidney disease: improvements in lean body mass and cytokine profile. Endocrinology. 2008;149:827-35 pubmed
    ..We conclude that ghrelin treatment in uremia results in improved lean mass accrual in part due to suppressed muscle proteolysis and possibly related to antiinflammatory effects. ..
  4. Niquet J, Pérez Martínez L, Guerra M, Grouselle D, Joseph Bravo P, Charli J. Extracellular matrix proteins increase the expression of pro-TRH and pro-protein convertase PC1 in fetal hypothalamic neurons in vitro. Brain Res Dev Brain Res. 2000;120:49-56 pubmed
    ..In conclusion, we have shown that some ECM proteins increased pro-TRH level in vitro; this may contribute to the enhancement of pro-TRH levels observed early in vivo in the hypothalamus. ..
  5. Shennan K, Taylor N, Docherty K. Calcium- and pH-dependent aggregation and membrane association of the precursor of the prohormone convertase PC2. J Biol Chem. 1994;269:18646-50 pubmed
    b>PC2 is a subtilisin-like protease which is thought to be involved in the processing of prohormones and proneuropeptides in neuroendocrine cells...
  6. Zhan S, Zhao H, J White A, Minami M, Pignataro G, Yang T, et al. Defective neuropeptide processing and ischemic brain injury: a study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains. J Cereb Blood Flow Metab. 2009;29:698-706 pubmed publisher
    ..model in rats, brain ischemia-induced changes in expression levels of mRNA and protein, and activities of proprotein convertase 2 (PC2) in the cortex were examined...
  7. Breslin M, Lindberg I, Benjannet S, Mathis J, Lazure C, Seidah N. Differential processing of proenkephalin by prohormone convertases 1(3) and 2 and furin. J Biol Chem. 1993;268:27084-93 pubmed
    ..3-kDa fragment, and free Leu5-enkephalin. PC2 exhibited a more complete processing profile...
  8. Bailyes E, Shennan K, Usac E, Arden S, Guest P, Docherty K, et al. Differences between the catalytic properties of recombinant human PC2 and endogenous rat PC2. Biochem J. 1995;309 ( Pt 2):587-94 pubmed
    Human prohormone convertase PC2 was expressed in Xenopus oocytes and its properties were compared with those of the Type-2 endopeptidase of rat insulin secretory granules, previously identified as PC2 [Bennett, Bailyes, Nielson, Guest, ..
  9. Toorie A, Cyr N, Steger J, Beckman R, Farah G, Nillni E. The Nutrient and Energy Sensor Sirt1 Regulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis by Altering the Production of the Prohormone Convertase 2 (PC2) Essential in the Maturation of Corticotropin-releasing Hormone (CRH) from Its Prohormone in M. J Biol Chem. 2016;291:5844-59 pubmed publisher
    ..of its precursor pro-CRH by the action of two members of the family of prohormone convertases 1 and 2 (PC1 and PC2)...
  10. Shen X, Li Q, Brent G, Friedman T. Regulation of regional expression in rat brain PC2 by thyroid hormone/characterization of novel negative thyroid hormone response elements in the PC2 promoter. Am J Physiol Endocrinol Metab. 2005;288:E236-45 pubmed
    The prohormone convertases (PCs) PC1 and PC2 are involved in the tissue-specific endoproteolytic processing of neuropeptide precursors within the secretory pathway...
  11. Marandi M, Mowla S, Tavallaei M, Yaghoobi M, Jafarnejad S. Proprotein convertases 1 and 2 (PC1 and PC2) are expressed in neurally differentiated rat bone marrow stromal stem cells (BMSCs). Neurosci Lett. 2007;420:198-203 pubmed
    ..In contrast, while PC1/PC3 and PC2 (specific to neural and endocrine cells) are absent in undifferentiated BMSCs, their expression is initiated upon ..
  12. Fujimaki T, Kato K, Yokoi K, Oguri M, Yoshida T, Watanabe S, et al. Association of genetic variants in SEMA3F, CLEC16A, LAMA3, and PCSK2 with myocardial infarction in Japanese individuals. Atherosclerosis. 2010;210:468-73 pubmed publisher
    ..of CLEC16A (rs9925481), the A-->G polymorphism of LAMA3 (rs12373237), and the C-->G polymorphism of PCSK2 (rs6080699) were significantly (false discovery rate for allele frequencies of <0.05) associated with MI...
  13. Winters A, Ramos Molina B, Jarvela T, Yerges Armstrong L, Pollin T, Lindberg I. Functional analysis of PCSK2 coding variants: A founder effect in the Old Order Amish population. Diabetes Res Clin Pract. 2017;131:82-90 pubmed publisher
    In humans, noncoding variants of PCSK2, the gene encoding prohormone convertase 2 (PC2), have been previously associated with risk for and age of onset of type 2 diabetes (T2D)...
  14. Cain B, Connolly K, Blum A, Vishnuvardhan D, Marchand J, Beinfeld M, et al. Distribution and colocalization of cholecystokinin with the prohormone convertase enzymes PC1, PC2, and PC5 in rat brain. J Comp Neurol. 2003;467:307-25 pubmed
    ..and synthetic substrates in vitro have pointed to the subtilisin/kexin-like enzymes prohormone convertase (PC) 1, PC2, and PC5 as potential candidates for these endoproteolytic cleavages...
  15. Pritchard L, Turnbull A, White A. Pro-opiomelanocortin processing in the hypothalamus: impact on melanocortin signalling and obesity. J Endocrinol. 2002;172:411-21 pubmed
    ..We predict that further research into hypothalamic POMC processing, and the proteolytic enzymes involved, may yield important new clues on how flux through the MC4R pathway is regulated. ..
  16. Lansac G, Dong W, Dubois C, Benlarbi N, Afonso C, Fournier I, et al. Lipopolysaccharide mediated regulation of neuroendocrine associated proprotein convertases and neuropeptide precursor processing in the rat spleen. J Neuroimmunol. 2006;171:57-71 pubmed
    ..Within the PC family, PC1/3 and PC2 are well known for their preferential expression within neuroendocrine cells...
  17. Sanchez V, Goldstein J, Stuart R, Hovanesian V, Huo L, Munzberg H, et al. Regulation of hypothalamic prohormone convertases 1 and 2 and effects on processing of prothyrotropin-releasing hormone. J Clin Invest. 2004;114:357-69 pubmed
    ..larger inactive precursor, its maturation requires proteolytic cleavage by prohormone convertases 1 and 2 (PC1 and PC2)...
  18. Rhodes C, Lincoln B, Shoelson S. Preferential cleavage of des-31,32-proinsulin over intact proinsulin by the insulin secretory granule type II endopeptidase. Implication of a favored route for prohormone processing. J Biol Chem. 1992;267:22719-27 pubmed
  19. Benjannet S, Rondeau N, Paquet L, Boudreault A, Lazure C, Chretien M, et al. Comparative biosynthesis, covalent post-translational modifications and efficiency of prosegment cleavage of the prohormone convertases PC1 and PC2: glycosylation, sulphation and identification of the intracellular site of prosegment cleavage of PC1 . Biochem J. 1993;294 ( Pt 3):735-43 pubmed
    We present herein the pulse-chase analysis of the biosynthesis of the prohormone convertases PC1 and PC2 in the endocrine GH4C1 cells infected with vaccinia virus recombinants expressing these convertases...
  20. Malide D, Seidah N, Chretien M, Bendayan M. Electron microscopic immunocytochemical evidence for the involvement of the convertases PC1 and PC2 in the processing of proinsulin in pancreatic beta-cells. J Histochem Cytochem. 1995;43:11-9 pubmed
    ..Two endoproteases, PC1 (or PC3) and PC2, have recently been implicated in the conversion of proinsulin...
  21. Hakes D, Birch N, Mezey A, Dixon J. Isolation of two complementary deoxyribonucleic acid clones from a rat insulinoma cell line based on similarities to Kex2 and furin sequences and the specific localization of each transcript to endocrine and neuroendocrine tissues in rats. Endocrinology. 1991;129:3053-63 pubmed
    ..5-kb cDNA coding for a 636-amino acid protein, which was found to be the rat equivalent of the human insulinoma PC2 protein, were isolated...
  22. Lee S, Hwang J, Lindberg I. Neuroendocrine protein 7B2 can be inactivated by phosphorylation within the secretory pathway. J Biol Chem. 2006;281:3312-20 pubmed
    ..Prohormone convertase-2 (PC2) is the only convertase that requires the expression of another neuroendocrine protein, 7B2, for expression of ..
  23. Wachira S, Temoney S, Ramlochansingh C, Hughes Darden C. Prevalence of melanocortin system transcripts in rat salt homeostasis endocrine tissues. Cell Mol Biol (Noisy-le-grand). 2007;53:8-14 pubmed
    ..Expression levels of pro-opiomelanocortin (POMC), POMC processing enzymes prohormone convertases 1 and 2 (PC1/PC2), melanocortin 3 receptor (MC3R) and melanocortin 5 receptor (MC5R) were not significantly affected by high dietary ..
  24. Nakashima M, Nie Y, Li Q, Friedman T. Up-regulation of splenic prohormone convertases PC1 and PC2 in diabetic rats. Regul Pept. 2001;102:135-45 pubmed
    ..treated rats with intraperitoneal streptozotocin (STZ) (50 mg/kg/day) daily for 5 days and measured splenic PC1 and PC2 mRNA by ribonuclease protection assay. We found that PC1 mRNA was increased 6.0+/-0.02-fold (P<0...
  25. Arias A, Vélez Granell C, Mayer G, Bendayan M. Colocalization of chaperone Cpn60, proinsulin and convertase PC1 within immature secretory granules of insulin-secreting cells suggests a role for Cpn60 in insulin processing. J Cell Sci. 2000;113 ( Pt 11):2075-83 pubmed
  26. Schaner P, Todd R, Seidah N, Nillni E. Processing of prothyrotropin-releasing hormone by the family of prohormone convertases. J Biol Chem. 1997;272:19958-68 pubmed
    ..We have also demonstrated that recombinant PC1 and PC2 process partially purified pro-TRH to cryptic peptides in vitro and that pro-TRH and PC1 mRNAs are coexpressed in ..
  27. Yoshida H, Ohagi S, Sanke T, Furuta H, Furuta M, Nanjo K. Association of the prohormone convertase 2 gene (PCSK2) on chromosome 20 with NIDDM in Japanese subjects. Diabetes. 1995;44:389-93 pubmed
    ..is converted to insulin by the concerted action of two sequence-specific subtilisin-like proteases termed prohormone convertase 2 (PC2) and prohormone convertase 3...
  28. Bloomquist B, Eipper B, Mains R. Prohormone-converting enzymes: regulation and evaluation of function using antisense RNA. Mol Endocrinol. 1991;5:2014-24 pubmed
    ..peptide-processing endoproteases have been identified by homology to the yeast Kex2 endoprotease, including furin, PC2, and PC1. However, the question is still open as to which might be involved in peptide posttranslational processing...