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Furin is a protein that in humans is encoded by the FURIN gene. Some proteins are inactive when they are first synthesized, and must have sections removed in order to become active. Furin cleaves these sections and activates the proteins.[1][2][3][4] 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. Furin is also known as PACE (Paired basic Amino acid Cleaving Enzyme).


The protein encoded by this gene is an enzyme which 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. A furin-like pro-protein convertase has been implicated in the processing of RGMc (also called hemojuvelin), a gene involved in a severe iron-overload disorder called juvenile hemochromatosis. Both the Ganz and Rotwein groups demonstrated that furin-like proprotein convertases (PPC) are responsible for conversion of 50 kDa HJV to a 40 kDa protein with a truncated COOH-terminus, at a conserved polybasic RNRR site. This suggests a potential mechanism to generate the soluble forms of HJV/hemojuvelin (s-hemojuvelin) found in the blood of rodents and humans.[5][6]

Furin is one of the proteases responsible for the proteolytic cleavage of HIV envelope polyprotein precursor gp160 to gp120 and gp41 prior to viral assembly.[7] This gene is thought to play a role in tumor progression. The use of alternate polyadenylation sites has been found for this gene.[3]

Furin is enriched in the Golgi apparatus, where it functions to cleave other proteins into their mature/active forms.[8] 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, dengue fever and several filoviruses including ebola and marburg virus 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.[9]

The furin substrates and the locations of furin cleavage sites in protein sequences can be predicted by two bioinformatics methods: ProP [10] and PiTou.[11]

Expression of furin in T-cells is required for maintenance of peripheral immune tolerance.[12]


Furin has been shown to interact with PACS1.[13]


  1. Wise RJ, Barr PJ, Wong PA, Kiefer MC, Brake AJ, Kaufman RJ (Dec 1990). "Expression of a human proprotein processing enzyme: correct cleavage of the von Willebrand factor precursor at a paired basic amino acid site". Proceedings of the National Academy of Sciences of the United States of America. 87 (23): 9378–82. doi:10.1073/pnas.87.23.9378. PMC 55168. PMID 2251280.
  2. Kiefer MC, Tucker JE, Joh R, Landsberg KE, Saltman D, Barr PJ (Dec 1991). "Identification of a second human subtilisin-like protease gene in the fes/fps region of chromosome 15". DNA and Cell Biology. 10 (10): 757–69. doi:10.1089/dna.1991.10.757. PMID 1741956.
  3. 3.0 3.1 "Entrez Gene: FURIN furin (paired basic amino acid cleaving enzyme)".
  4. Roebroek AJ, Schalken JA, Leunissen JA, Onnekink C, Bloemers HP, Van de Ven WJ (Sep 1986). "Evolutionary conserved close linkage of the c-fes/fps proto-oncogene and genetic sequences encoding a receptor-like protein". The EMBO Journal. 5 (9): 2197–202. PMC 1167100. PMID 3023061.
  5. Lin L, Nemeth E, Goodnough JB, Thapa DR, Gabayan V, Ganz T (2008). "Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site". Blood Cells, Molecules & Diseases. 40 (1): 122–31. doi:10.1016/j.bcmd.2007.06.023. PMC 2211380. PMID 17869549.
  6. Kuninger D, Kuns-Hashimoto R, Nili M, Rotwein P (2008). "Pro-protein convertases control the maturation and processing of the iron-regulatory protein, RGMc/hemojuvelin". BMC Biochemistry. 9: 9. doi:10.1186/1471-2091-9-9. PMC 2323002. PMID 18384687.
  7. Hallenberger S, Bosch V, Angliker H, Shaw E, Klenk HD, Garten W (Nov 1992). "Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160". Nature. 360 (6402): 358–61. doi:10.1038/360358a0. PMID 1360148.
  8. Thomas G (Oct 2002). "Furin at the cutting edge: from protein traffic to embryogenesis and disease". Nature Reviews Molecular Cell Biology. 3 (10): 753–66. doi:10.1038/nrm934. PMC 1964754. PMID 12360192.
  9. Shiryaev SA, Remacle AG, Ratnikov BI, Nelson NA, Savinov AY, Wei G, Bottini M, Rega MF, Parent A, Desjardins R, Fugere M, Day R, Sabet M, Pellecchia M, Liddington RC, Smith JW, Mustelin T, Guiney DG, Lebl M, Strongin AY (Jul 2007). "Targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogens". The Journal of Biological Chemistry. 282 (29): 20847–53. doi:10.1074/jbc.M703847200. PMID 17537721.
  10. Duckert P, Brunak S, Blom N (Jan 2004). "Prediction of proprotein convertase cleavage sites". Protein Engineering, Design & Selection. 17 (1): 107–112. doi:10.1093/protein/gzh013. PMID 14985543.
  11. Tian S, Huajun W, Wu J (February 2012). "Computational prediction of furin cleavage sites by a hybrid method and understanding mechanism underlying diseases". Scientific Reports. 2. doi:10.1038/srep00261. PMC 3281273. PMID 22355773.
  12. Pesu M, Watford WT, Wei L, Xu L, Fuss I, Strober W, Andersson J, Shevach EM, Quezado M, Bouladoux N, Roebroek A, Belkaid Y, Creemers J, O'Shea JJ (Sep 2008). "T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance". Nature. 455 (7210): 246–50. doi:10.1038/nature07210. PMC 2758057. PMID 18701887.
  13. Wan L, Molloy SS, Thomas L, Liu G, Xiang Y, Rybak SL, Thomas G (Jul 1998). "PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization". Cell. 94 (2): 205–16. doi:10.1016/S0092-8674(00)81420-8. PMID 9695949.

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