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Furin is a subtilisin-like proprotein processing enzyme in higher eukaryotes

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Abstract

The human fur gene encodes a protein, designated furin, the C-terminal half of which contains a transmembrane and a cysteine-rich receptor-like domain. The N-terminal half of furin exhibits striking primary amino acid sequence similarity to the catalytic domains of members of the subtilisin family of serine proteases. We here report characteristics of the furin protein and propose a three-dimensional model for its presumptive catalytic domain with characteristics, that predict furin to exhibit an endo-proteolytic cleavage selectivity at paired basic residues. This prediction is substantiated by transfection and cotransfection experiments, using COS-1 cells. Full length fur cDNA evokes the specific synthesis of two polypeptides of about 100 kDa and 90 kDa as appeared from Western blot analysis of transfected COS-1 cells using a polyclonal anti-furin antiserum. Functional analysis of furin was performed by cotransfection of fur cDNA with cDNA encoding the ‘wild type’ precursor of von Willebrand factor (pro-vWF) and revealed an increased proteolytic processing of prov WF. In contrast, cotransfection of fur cDNA with a recombinat derivative (provWFgly763), having the arginine residue adjacent to the proteolytic cleavage site (arg-ser-lys-arg) replaced by glycine, revealed that provWFgly763 is not processed by the fur gene product. We conclude that in higher eukaryotes, furin is the prototype of a subtilisin-like class of proprotein processing enzymes with substrate specificity for paired basic residues.

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References

  1. BathurstIC, BrennanSO, CarrellRW, CousensLS, BrakeAJ & BarrPJ (1987) Science 235: 348–350

    Google Scholar 

  2. BottR, UltschM, KossiakofA, GraycarT, KatzB & PowerS (1988) J. Biol. Chem. 263: 7895–7906

    Google Scholar 

  3. BrennanSO & PeachRJ (1988) FEBS Lett. 229: 167–170

    Google Scholar 

  4. BriedigkeitL & FrömmelC (1989) FEBS Lett. 253: 83–87

    Google Scholar 

  5. DavidsonHW, RhodesCJ & HuttonJC (1988) Nature 333: 93–96

    Google Scholar 

  6. DochertyK & SteinerDF (1982) Annu. Rev. Physiol. 44: 625–638

    Google Scholar 

  7. DoolittleRF (1985) Trends Biochem Sci. 10: 233–237

    Google Scholar 

  8. DouglasJ, CivelliO & HerbertE (1984) Annu. Rev. Biochem. 53: 665–715

    Google Scholar 

  9. FosterDC, SprecherCA, HollyRD, GambeeJE, WalkerKM & KumarAA (1990) Biochemistry 29: 347–354

    Google Scholar 

  10. FullerRS, SterneRE & ThornerJ (1988) Annu Rev. Physiol. 50: 345–362

    Google Scholar 

  11. FullerRS, BrakeAJ & ThornerJ (1989) Science 246: 482–486

    Google Scholar 

  12. GrosP, BetzelCh, DauterZ, WilsonKS & HolWGJ (1989) J. Mol. Biol. 210: 347–367

    Google Scholar 

  13. HudsonP, HaleyJ, CrankM, ShineJ & NiallH (1981) Nature 291: 127–131

    Google Scholar 

  14. HigginsDG & SharpPM (1988) Gene 73: 237–244

    Google Scholar 

  15. IkeharaY, OdaK & KatoK (1976) Biochem. Biophys. Res. Commun. 72: 319–326

    Google Scholar 

  16. IrwinDM, RobertsonKA & MacGillivrayRTAJ (1988) Mol. Biol. 200: 31–45

    Google Scholar 

  17. JacobsM, EliassonM, UhlenM & FlockJ-I (1985) Nucl. Acids Res. 13: 8913–8926

    Google Scholar 

  18. JornvallH, CarlquistM, KwaukS, OtteSC, McIntoshCHS, BrownJC & MuttV (1981) FEBS Lett. 123: 205–210

    Google Scholar 

  19. JuliusD, BrakeA, BlairL, KunisawaR & ThornerJ (1984) Cell 37: 1075–1089

    Google Scholar 

  20. KabschW & SanderC (1983) Biopolymers 22: 2577–2637

    Google Scholar 

  21. LuthmanH & MagnussonG (1983) Nucl. Acids Res. 11: 1295–1308

    Google Scholar 

  22. McPhalenCA & JamesMNG (1988) Biochemistry 27: 6582–6598

    Google Scholar 

  23. MelounB, BaudysM, KostkaV, HausdorfG, FrömmelC & HöhneWE (1985) FEBS Lett. 183: 195–200

    Google Scholar 

  24. MizunoK, NakamuraT, OshimaT, TanakaS & MatsuoH (1988) Biochem. Biophys. Res. Commun. 156: 246–254

    Google Scholar 

  25. OdaK & IkeharaY (1988) J. Biochem. 104: 159–161

    Google Scholar 

  26. QuinnPS & JudahJD (1978) Biochem. J. 172: 301–309

    Google Scholar 

  27. RholamM, NocolasP & CohenP (1986) FEBS Lett. 207: 1–5

    Google Scholar 

  28. RichardsonJS (1981) Adv. Prot. Chem. 34: 168–339

    Google Scholar 

  29. RoebroekAJM, SchalkenJA, BussemakersMJG, VanHeerikhuizenH, OnnekinkC, DebruyneFMJ, BloemersHPJ & Van deVenWJM (1986) Molec. Biol. Rep. 11: 117–125

    Google Scholar 

  30. RoebroekAJM, SchalkenJA, LeunissenJAM, OnnekinkC, BloemersHPJ & Van deVenWJM (1986) EMBO J. 5: 2197–2202

    Google Scholar 

  31. SchalkenJA, RoebroekAJM, OomenPPCA, WagenaarSSC, DebruyneFMJ, BloemersHPJ & Van deVenWJM (1987) J. Clin. Invest. 80: 1545–1549

    Google Scholar 

  32. SchalkenJA, Van denOuwelandAMW, DeJongMEM, VanGroningenJJM, VanBokhovenA & Van deVenWJM (1988) Live Mol. Genet. 7: 111–116

    Google Scholar 

  33. SmeekensSP & SteinerDF (1990) J. Biol. Chem. 265: 2997–3000

    Google Scholar 

  34. SossinWS, FisherJM & SchellerRH (1989) Neuron 2: 1407–11417

    Google Scholar 

  35. Tanguy-RougeauC, Wesolowski-LouvelM & FukuharaH (1988) FEBS Lett. 234: 464–470

    Google Scholar 

  36. ThomasG, ThorneBA, ThomasL, AllenRG, HrubyDE, FullerR & ThornerJ (1988) Science 241: 226–230

    Google Scholar 

  37. Van denOuwelandAMW, VanGroningenJJM, RoebroekAJM, OnnekinkC & Van deVenWJM (1989) Nucl. Acids Res. 17: 7101–7102

    Google Scholar 

  38. Van denOuwelandAMW, VanDuijnhovenJLP, KeizerGD, DorssersLCJ & Van deVenWJM (1990) Nucl. Acids Res. 18: 664

    Google Scholar 

  39. VerweijCL, DiergaardePJ, HartM & PannekoekH (1986) EMBO J. 5: 1839–1847

    Google Scholar 

  40. VerweijCL, HartM & PannekoekHJ (1988) Biol. Chem. 263: 7921–7924

    Google Scholar 

  41. VoorbergJ, FontijnR, VanMourikJA & PannekoekH (1990) EMBO J. 9: 797–803

    Google Scholar 

  42. WellsJA, FerrariE, HennerDJ, EstellDA & ChenEY (1983) Nucl. Acids Res. 11: 7911–7925

    Google Scholar 

  43. WellsJA, CunninghamBC, GraycarTP & EstellDA (1987) Proc. Natl. Acad. Sci. USA 84: 5167–5171

    Google Scholar 

  44. WellsJA & EstellDA (1988) Trends Biochem. Sci. 13: 291–297

    Google Scholar 

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van de Ven, W.J.M., Voorberg, J., Fontijn, R. et al. Furin is a subtilisin-like proprotein processing enzyme in higher eukaryotes. Mol Biol Rep 14, 265–275 (1990). https://doi.org/10.1007/BF00429896

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