Furin

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Furin (paired basic amino acid cleaving enzyme)
PDB rendering based on 1p8j.
Available structures: 1p8j
Identifiers
Symbol(s) FURIN; FUR; PACE; PCSK3; SPC1
External IDs OMIM: 136950 MGI: 97513 HomoloGene: 1930
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 5045 18550
Ensembl ENSG00000140564 ENSMUSG00000030530
Uniprot P09958 Q6GTN6
Refseq NM_002569 (mRNA)
NP_002560 (protein)		 XM_980423 (mRNA)
XP_985517 (protein)
Location Chr 15: 89.21 - 89.23 Mb Chr 7: 80.26 - 80.28 Mb
Pubmed search [1] [2]

Furin (paired basic amino acid cleaving enzyme), also known as FURIN, is a human gene. The protein encoded by this gene belongs to the subtilisin-like proprotein convertase family. The members of this family are proprotein convertases that process latent precursor proteins into their biologically active products. This encoded protein is a calcium-dependent serine endoprotease that can efficiently cleave precursor proteins at their paired basic amino acid processing sites. Some of its substrates are: proparathyroid hormone, transforming growth factor beta 1 precursor, proalbumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, beta subunit of pro-nerve growth factor and von Willebrand factor. It is also thought to be one of the proteases responsible for the activation of HIV envelope glycoproteins gp160 and gp140. This gene is thought to play a role in tumor progression. The use of alternate polyadenylation sites has been found for this gene.[1]


Furin is enriched in the Golgi apparatus, where it functions to cleave other proteins into their mature/active forms. Furin cleaves proteins just downstream of a basic amino acid target sequence (canonically, Arg-X-(Arg/Lys) -Arg'). In addition to processing cellular precursor proteins, furin is also utilized by a number of pathogens. For example, the envelope proteins of viruses such as HIV, influenza and dengue fever viruses must be cleaved by furin or furin-like proteases to become fully functional. Anthrax toxin, Pseudomonas exotoxin, and papillomaviruses must be processed by furin during their initial entry into host cells. Inhibitors of furin are under consideration as therapeutic agents for treating anthrax infection.

Furin is also known as PACE, Paired basic Amino acid Cleaving Enzyme. It was named furin because it was in the upstream region of an oncogene known as FES. The gene was known as FUR (FES Upstream Region) and therefore the protein was named furin.

[edit] References

  1. ^ Entrez Gene: FURIN furin (paired basic amino acid cleaving enzyme).

[edit] Further reading

  • Nakayama K (1998). "Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins.". Biochem. J. 327 ( Pt 3): 625–35. PMID 9599222. 
  • Bassi DE, Mahloogi H, Klein-Szanto AJ (2000). "The proprotein convertases furin and PACE4 play a significant role in tumor progression.". Mol. Carcinog. 28 (2): 63–9. PMID 10900462. 
  • Hallenberger S, Bosch V, Angliker H, et al. (1992). "Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160.". Nature 360 (6402): 358–61. doi:10.1038/360358a0. PMID 1360148. 
  • Rehemtulla A, Kaufman RJ (1992). "Preferred sequence requirements for cleavage of pro-von Willebrand factor by propeptide-processing enzymes.". Blood 79 (9): 2349–55. PMID 1571548. 
  • Leduc R, Molloy SS, Thorne BA, Thomas G (1992). "Activation of human furin precursor processing endoprotease occurs by an intramolecular autoproteolytic cleavage.". J. Biol. Chem. 267 (20): 14304–8. PMID 1629222. 
  • Barr PJ, Mason OB, Landsberg KE, et al. (1991). "cDNA and gene structure for a human subtilisin-like protease with cleavage specificity for paired basic amino acid residues.". DNA Cell Biol. 10 (5): 319–28. PMID 1713771. 
  • Kiefer MC, Tucker JE, Joh R, et al. (1992). "Identification of a second human subtilisin-like protease gene in the fes/fps region of chromosome 15.". DNA Cell Biol. 10 (10): 757–69. PMID 1741956. 
  • Herz J, Kowal RC, Goldstein JL, Brown MS (1990). "Proteolytic processing of the 600 kd low density lipoprotein receptor-related protein (LRP) occurs in a trans-Golgi compartment.". EMBO J. 9 (6): 1769–76. PMID 2112085. 
  • Wise RJ, Barr PJ, Wong PA, et al. (1991). "Expression of a human proprotein processing enzyme: correct cleavage of the von Willebrand factor precursor at a paired basic amino acid site.". Proc. Natl. Acad. Sci. U.S.A. 87 (23): 9378–82. PMID 2251280. 
  • van den Ouweland AM, van Duijnhoven HL, Keizer GD, et al. (1990). "Structural homology between the human fur gene product and the subtilisin-like protease encoded by yeast KEX2.". Nucleic Acids Res. 18 (3): 664. PMID 2408021. 
  • Van den Ouweland AM, Van Groningen JJ, Roebroek AJ, et al. (1989). "Nucleotide sequence analysis of the human fur gene.". Nucleic Acids Res. 17 (17): 7101–2. PMID 2674906. 
  • Roebroek AJ, Schalken JA, Leunissen JA, et al. (1986). "Evolutionary conserved close linkage of the c-fes/fps proto-oncogene and genetic sequences encoding a receptor-like protein.". EMBO J. 5 (9): 2197–202. PMID 3023061. 
  • Molloy SS, Thomas L, VanSlyke JK, et al. (1994). "Intracellular trafficking and activation of the furin proprotein convertase: localization to the TGN and recycling from the cell surface.". EMBO J. 13 (1): 18–33. PMID 7508380. 
  • Brakch N, Dettin M, Scarinci C, et al. (1995). "Structural investigation and kinetic characterization of potential cleavage sites of HIV GP160 by human furin and PC1.". Biochem. Biophys. Res. Commun. 213 (1): 356–61. PMID 7639757. 
  • Takahashi S, Kasai K, Hatsuzawa K, et al. (1993). "A mutation of furin causes the lack of precursor-processing activity in human colon carcinoma LoVo cells.". Biochem. Biophys. Res. Commun. 195 (2): 1019–26. doi:10.1006/bbrc.1993.2146. PMID 7690548. 
  • Hendy GN, Bennett HP, Gibbs BF, et al. (1995). "Proparathyroid hormone is preferentially cleaved to parathyroid hormone by the prohormone convertase furin. A mass spectrometric study.". J. Biol. Chem. 270 (16): 9517–25. PMID 7721880. 
  • Dubois CM, Laprise MH, Blanchette F, et al. (1995). "Processing of transforming growth factor beta 1 precursor by human furin convertase.". J. Biol. Chem. 270 (18): 10618–24. PMID 7737999. 
  • Gu M, Rappaport J, Leppla SH (1995). "Furin is important but not essential for the proteolytic maturation of gp160 of HIV-1.". FEBS Lett. 365 (1): 95–7. PMID 7774724. 
  • Schäfer W, Stroh A, Berghöfer S, et al. (1995). "Two independent targeting signals in the cytoplasmic domain determine trans-Golgi network localization and endosomal trafficking of the proprotein convertase furin.". EMBO J. 14 (11): 2424–35. PMID 7781597. 
  • Mbikay M, Seidah NG, Chrétien M, Simpson EM (1995). "Chromosomal assignment of the genes for proprotein convertases PC4, PC5, and PACE 4 in mouse and human.". Genomics 26 (1): 123–9. PMID 7782070. 
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