Furin

Summary

Gene Symbol: Furin
Description: furin (paired basic amino acid cleaving enzyme)
Alias: Pace, Pcsk3, furin, Paired basic amino acid cleaving enzyme (furin), Proprotein convertase subtilisin/kexin type 3 (paired basic amino acid cleaving enzyme, furin, membrane associated receptor protein), dibasic-processing enzyme, paired basic amino acid residue-cleaving enzyme, prohormone convertase 3, proprotein convertase subtilisin/kexin type3
Species: rat
Products:     Furin

Top Publications

  1. Kelty B, Curry T. Ovarian furin (proprotein convertase subtilisin/kexin type3): expression, localization, and potential role in ovulation in the rat. Biol Reprod. 2010;83:147-54 pubmed publisher
    The process of ovulation involves weakening of the follicular wall by proteolytic enzymes. The function of FURIN (also known as PCSK3) is to activate various proteolytic enzymes...
  2. Lopez De Cicco R, Bassi D, Zucker S, Seidah N, Klein Szanto A. Human carcinoma cell growth and invasiveness is impaired by the propeptide of the ubiquitous proprotein convertase furin. Cancer Res. 2005;65:4162-71 pubmed
    b>Furin, a potent proprotein convertase involved in activation of several cancer-related substrates, is synthesized as an inactive zymogen, thus minimizing the occurrence of premature enzymatic activity that would lead to inappropriate ..
  3. Decroly E, Wouters S, Di Bello C, Lazure C, Ruysschaert J, Seidah N. Identification of the paired basic convertases implicated in HIV gp160 processing based on in vitro assays and expression in CD4(+) cell lines. J Biol Chem. 1996;271:30442-50 pubmed
    ..The data demonstrate that furin, PC5/6, and the newly cloned PC7 are the main transcribed convertases, suggesting that these proteinases are the ..
  4. Silvestri L, Pagani A, Camaschella C. Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis. Blood. 2008;111:924-31 pubmed
    ..However, the mechanisms regulating the 2 HJV isoforms remain unclear. Here we show that s-HJV originates from a furin cleavage at position 332-335...
  5. Gendron F, Mongrain S, Laprise P, McMahon S, Dubois C, Blais M, et al. The CDX2 transcription factor regulates furin expression during intestinal epithelial cell differentiation. Am J Physiol Gastrointest Liver Physiol. 2006;290:G310-8 pubmed
    ..In this study, we show that the proprotein convertase furin, involved in proteolytic maturation of proprotein substrates including LPH and cell surface proteins, is a CDX2 ..
  6. 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
    ..Ex vivo data showed that human PCSK9 is inactivated by cleavage at Arg(218)? by the overexpressed convertases furin and PC5/6A...
  7. Wan L, Molloy S, Thomas L, Liu G, Xiang Y, Rybak S, et al. PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization. Cell. 1998;94:205-16 pubmed
    ..PACS-1 directs the TGN localization of furin by binding to the protease's phosphorylated cytosolic domain...
  8. Kim S, Wang R, Gordon D, Bass J, Steiner D, Lynn D, et al. Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementia. Nat Neurosci. 1999;2:984-8 pubmed
    ..that both BRI-L and its wild-type counterpart, BRI, were constitutively processed by the proprotein convertase, furin, resulting in the secretion of carboxyl-terminal peptides that encompass all or part of ABri...
  9. Zhong M, Munzer J, Basak A, Benjannet S, Mowla S, Decroly E, et al. The prosegments of furin and PC7 as potent inhibitors of proprotein convertases. In vitro and ex vivo assessment of their efficacy and selectivity. J Biol Chem. 1999;274:33913-20 pubmed
    ..In this work, we examined inhibition by purified, recombinant bacterial prosegments of furin and PC7 on the in vitro processing of either the fluorogenic peptide pERTKR-MCA or the human immunodeficiency ..

More Information

Publications34

  1. Wang P, Tortorella M, England K, Malfait A, Thomas G, Arner E, et al. Proprotein convertase furin interacts with and cleaves pro-ADAMTS4 (Aggrecanase-1) in the trans-Golgi network. J Biol Chem. 2004;279:15434-40 pubmed
    ..In this study, by using both furin-specific inhibitor and RNA interference technique, we demonstrate that furin plays an important role in the ..
  2. Wickham L, Benjannet S, Marcinkiewicz E, Chretien M, Seidah N. Beta-amyloid protein converting enzyme 1 and brain-specific type II membrane protein BRI3: binding partners processed by furin. J Neurochem. 2005;92:93-102 pubmed
    ..Furthermore, pulse and pulse-chase analyses revealed that the pro-protein convertases furin, and to a lesser extent PC7 and PC5A, process BRI3 into a C-terminal secreted approximately 4-kDa product...
  3. Mayer G, Boileau G, Bendayan M. Furin interacts with proMT1-MMP and integrin alphaV at specialized domains of renal cell plasma membrane. J Cell Sci. 2003;116:1763-73 pubmed
    ..Both membrane type-1 MMP (MT1-MMP) and the integrin alphaV subunit are fully activated upon cleavage at a furin recognition site...
  4. Beck S, Le Good J, Guzman M, Ben Haim N, Roy K, Beermann F, et al. Extraembryonic proteases regulate Nodal signalling during gastrulation. Nat Cell Biol. 2002;4:981-5 pubmed
    ..Here we show that the proprotein convertases Spc1 and Spc4 (also known as Furin and Pace4, respectively) are expressed in adjacent extraembryonic ectoderm...
  5. 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
    ..mutations R218S, F216L, and D374Y associated with hypercholesterolemia result in total or partial loss of furin/PC5/6A processing at the motif RFHR218 downward arrow...
  6. 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
    ..processing, recombinant vaccinia viruses were used to coexpress the prohormone convertases PC1, PC2, PACE4, PC5-B, furin, or control dynorphin together with rat prepro-TRH in constitutively secreting LoVo cells or in the regulated ..
  7. Tellier E, Canault M, Rebsomen L, Bonardo B, Juhan Vague I, Nalbone G, et al. The shedding activity of ADAM17 is sequestered in lipid rafts. Exp Cell Res. 2006;312:3969-80 pubmed
    ..ADAM17 is included in cholesterol-rich membrane microdomains (lipid rafts) where its prodomain is cleaved by furin. Consequently, ADAM17 shedding activity is sequestered in lipid rafts, which is confirmed by the fact that ..
  8. Stawowy P, Kallisch H, Borges Pereira Stawowy N, Stibenz D, Veinot J, Grafe M, et al. Immunohistochemical localization of subtilisin/kexin-like proprotein convertases in human atherosclerosis. Virchows Arch. 2005;446:351-9 pubmed
    ..In vitro, the subtilisin/kexin-like proprotein convertases (PCs), namely PC5 and furin, have been shown to be responsible for the endoproteolytic activation of the alpha(v) integrin subunit...
  9. Essalmani R, Susan Resiga D, Chamberland A, Asselin M, Canuel M, Constam D, et al. Furin is the primary in vivo convertase of angiopoietin-like 3 and endothelial lipase in hepatocytes. J Biol Chem. 2013;288:26410-8 pubmed publisher
    The proprotein convertases (PCs) furin, PC5/6, and PACE4 exhibit unique and/or complementary functions...
  10. Stawowy P, Margeta C, Kallisch H, Seidah N, Chretien M, Fleck E, et al. Regulation of matrix metalloproteinase MT1-MMP/MMP-2 in cardiac fibroblasts by TGF-beta1 involves furin-convertase. Cardiovasc Res. 2004;63:87-97 pubmed
    ..b>Furin, a subtilisin/kexin-like proprotein convertase (PC), activates TGF-beta1 and membrane-bound MT1-MMP, which ..
  11. Posner S, Vaslet C, Jurofcik M, Lee A, Seidah N, Nillni E. Stepwise posttranslational processing of progrowth hormone-releasing hormone (proGHRH) polypeptide by furin and PC1. Endocrine. 2004;23:199-213 pubmed
    ..We found that in the absence of furin (LoVo cells) or CHO cells treated with BFA, only one moiety was observed, and that corresponds to the same ..
  12. Anderson E, Molloy S, Jean F, Fei H, Shimamura S, Thomas G. The ordered and compartment-specfific autoproteolytic removal of the furin intramolecular chaperone is required for enzyme activation. J Biol Chem. 2002;277:12879-90 pubmed
    The propeptide of furin has multiple roles in guiding the activation of the endoprotease in vivo...
  13. 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
    Recombinant vaccinia virus vectors were used to coexpress mouse prohormone convertase 1 (mPC1), mPC2, or human furin together with human proenkephalin in GH4C1 cells (rat pituitary somatomammotrophs) to examine the proteolytic processing ..
  14. Stawowy P, Kallisch H, Kilimnik A, Margeta C, Seidah N, Chretien M, et al. Proprotein convertases regulate insulin-like growth factor 1-induced membrane-type 1 matrix metalloproteinase in VSMCs via endoproteolytic activation of the insulin-like growth factor-1 receptor. Biochem Biophys Res Commun. 2004;321:531-8 pubmed
    ..as larger precursor proproteins, which require endoproteolytic activation by the proprotein convertases (PCs) furin/PC5 to gain full biological activity...
  15. Koo B, Longpre J, Somerville R, Alexander J, Leduc R, Apte S. Cell-surface processing of pro-ADAMTS9 by furin. J Biol Chem. 2006;281:12485-94 pubmed
    Processing of polypeptide precursors by proprotein convertases (PCs) such as furin typically occurs within the trans-Golgi network. Here, we show in a variety of cell types that the propeptide of ADAMTS9 is not excised intracellularly...
  16. Boucher E, Mayer G, Londono I, Bendayan M. Expression and localization of MT1-MMP and furin in the glomerular wall of short- and long-term diabetic rats. Kidney Int. 2006;69:1570-7 pubmed
    ..to trace the expression and localization of membrane type-1 metalloprotease (MT1-MMP) and its activating enzyme furin, key proteins involved in basement membrane turnover, in short- and long-term diabetic rat renal tissues...
  17. Anderson E, VanSlyke J, Thulin C, Jean F, Thomas G. Activation of the furin endoprotease is a multiple-step process: requirements for acidification and internal propeptide cleavage. EMBO J. 1997;16:1508-18 pubmed
    Activation of furin requires autoproteolytic cleavage of its 83-amino acid propeptide at the consensus furin site, Arg-Thr-Lys-Arg107/. This RER-localized cleavage is necessary, but not sufficient, for enzyme activation...
  18. Yang T, Mendoza Londono R, Lu H, Tao J, Li K, Keller B, et al. E-selectin ligand-1 regulates growth plate homeostasis in mice by inhibiting the intracellular processing and secretion of mature TGF-beta. J Clin Invest. 2010;120:2474-85 pubmed publisher
    ..Furthermore, ESL-1 inhibited the processing of proTGF-beta by a furin-like protease, leading to reduced secretion of mature TGF-beta by primary mouse chondrocytes and HEK293 cells...
  19. Yang X, Wang Q, Gao Z, Zhou Z, Peng S, Chang W, et al. Proprotein convertase furin regulates apoptosis and proliferation of granulosa cells in the rat ovary. PLoS ONE. 2013;8:e50479 pubmed publisher
    ..b>Furin is a member of the subtilisin-like proteases that activate large numbers of proprotein substrates and is ..
  20. Misumi Y, Sohda M, Ikehara Y. Sequence of the cDNA encoding rat furin, a possible propeptide-processing endoprotease. Nucleic Acids Res. 1990;18:6719 pubmed
  21. Bowler R, Nicks M, Olsen D, Thøgersen I, Valnickova Z, Højrup P, et al. Furin proteolytically processes the heparin-binding region of extracellular superoxide dismutase. J Biol Chem. 2002;277:16505-11 pubmed
    ..Specific protease inhibitors and overexpression of intracellular proteases implicate furin as a processing protease...
  22. Lin E, Pei D, Huang Y, Hsieh C, Wu L. Gene-gene interactions among genetic variants from obesity candidate genes for nonobese and obese populations in type 2 diabetes. Genet Test Mol Biomarkers. 2009;13:485-93 pubmed publisher
    ..001). The results suggest that the single nucleotide polymorphisms from the obesity candidate genes may contribute to the risk of T2D independently and/or in an interactive manner according to the presence or absence of obesity. ..
  23. Kappert K, Furundzija V, Fritzsche J, Margeta C, Krüger J, Meyborg H, et al. Integrin cleavage regulates bidirectional signalling in vascular smooth muscle cells. Thromb Haemost. 2010;103:556-63 pubmed publisher
    ..The integrin av subunit is synthesised from its precursor via furin-dependent endoproteolytic cleavage...
  24. Seidah N, Benjannet S, Pareek S, Savaria D, Hamelin J, Goulet B, et al. Cellular processing of the nerve growth factor precursor by the mammalian pro-protein convertases. Biochem J. 1996;314 ( Pt 3):951-60 pubmed
    ..of nerve growth factor (proNGF), its biosynthesis and intracellular processing by the pro-protein convertases furin, PC1, PC2, PACE4, PC5 and the PC5 isoform PC5/6-B were analysed using the vaccinia virus expression system in ..
  25. Kato S, Zhang R, Roberts J. Proprotein convertases play an important role in regulating PKGI endoproteolytic cleavage and nuclear transport. Am J Physiol Lung Cell Mol Physiol. 2013;305:L130-40 pubmed publisher
    ..Therefore we investigated the role of PCs in regulating PKGI proteolysis. We observed that overexpression of PCs, furin and PC5, but not PC7, which are all expressed in SMC, increase PKGI cleavage in a dose-dependent manner in human ..