Furin is a protease, a proteolytic enzyme activated by substrate presentation that in humans and other animals 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.^[5][6][7][8] 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). A member of family S8, furin is a subtilisin-like peptidase.

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FURIN
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4OMC, 4OMD, 4RYD, 4Z2A
Identifiers
Aliases	FURIN, FUR, PACE, PCSK3, SPC1, furin, paired basic amino acid cleaving enzyme
External IDs	OMIM: 136950 MGI: 97513 HomoloGene: 1930 GeneCards: FURIN
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q26.1 Start 90,868,588 bp[1] End 90,883,458 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 D2|7 45.65 cM Start 80,038,333 bp[2] End 80,055,184 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver body of pancreas right lung right lobe of thyroid gland left lobe of thyroid gland upper lobe of left lung salivary gland anterior pituitary minor salivary gland monocyte Top expressed in epithelium of stomach parotid gland lip corneal stroma extensor digitorum longus muscle secondary oocyte ascending aorta gallbladder aortic valve ankle joint More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nerve growth factor binding peptide binding metal ion binding protease binding peptidase activity protein binding serine-type endopeptidase inhibitor activity serine-type peptidase activity hydrolase activity endopeptidase activity serine-type endopeptidase activity Cellular component integral component of membrane Golgi apparatus membrane plasma membrane cell surface trans-Golgi network endoplasmic reticulum Golgi lumen membrane raft trans-Golgi network transport vesicle extracellular exosome extracellular space Golgi membrane extracellular region endosome endosome membrane integral component of Golgi membrane Biological process negative regulation of low-density lipoprotein particle receptor catabolic process negative regulation of transforming growth factor beta1 production viral life cycle secretion by cell peptide biosynthetic process protein processing positive regulation of membrane protein ectodomain proteolysis extracellular matrix disassembly extracellular matrix organization viral protein processing proteolysis signal peptide processing peptide hormone processing regulation of signal transduction regulation of protein catabolic process collagen catabolic process negative regulation of nerve growth factor production nerve growth factor processing nerve growth factor production cell population proliferation transforming growth factor beta receptor signaling pathway regulation of endopeptidase activity negative regulation of endopeptidase activity cornification zymogen activation regulation of lipoprotein lipase activity dibasic protein processing zymogen inhibition positive regulation of transforming growth factor beta1 activation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5045 18550 Ensembl ENSG00000140564 ENSMUSG00000030530 UniProt P09958 P23188 RefSeq (mRNA) NM_002569 NM_001289823 NM_001289824 NM_001081454 NM_011046 RefSeq (protein) NP_001276752 NP_001276753 NP_002560 NP_001369548 NP_001369549 NP_001369550 NP_001369551 NP_001276752.1 NP_001276753.1 NP_002560.1 NP_001074923 NP_035176 Location (UCSC) Chr 15: 90.87 – 90.88 Mb Chr 7: 80.04 – 80.06 Mb PubMed search [3] [4]
Wikidata
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The protein encoded by this gene is an enzyme that 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.^[9][10]

The furin substrates and the locations of furin cleavage sites in protein sequences can be predicted by two bioinformatics methods: ProP^[11] and PiTou.^[12]

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.^[13] This protease is also thought to play a role in tumor progression.^[7] The use of alternate polyadenylation sites has been found for the FURIN gene.^{[citation needed]}

Furin is enriched in the Golgi apparatus, where it functions to cleave other proteins into their mature/active forms.^[14] 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 used by a number of pathogens. For example, the envelope proteins of viruses such as HIV, influenza, dengue fever, several filoviruses including ebola and marburg virus, and the spike protein of SARS-CoV-2,^[15][16][17] must be cleaved by furin or furin-like proteases to become fully functional. When SARS-CoV-2 virus is being synthesized in an infected cell, furin or furin-like proteases cleave the spike protein into two portions (S1 and S2), which remain associated.^[18]

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.^[19]

Furin is regulated by cholesterol and substrate presentation. When cholesterol is high, furin traffics to GM1 lipid rafts. When cholesterol is low, furin traffics to the disordered region.^[20] This is speculated to contribute to cholesterol and age dependent priming of SARS-CoV.

Expression of furin in T-cells is required for maintenance of peripheral immune tolerance.^[21]

Furin has been shown to interact with PACS1.^[22]