Furin (paired basic amino acid cleaving enzyme)
PDB rendering based on 1p8j.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1p8j
Identifiers
Symbols	FURIN; FUR; PACE; PCSK3; SPC1
External IDs	OMIM: 136950 MGI: 97513 HomoloGene: 1930 ChEMBL: 2611 GeneCards: FURIN Gene
EC number	3.4.21.75
Gene Ontology Molecular function • protease binding • endopeptidase activity • serine-type endopeptidase activity • serine-type endopeptidase activity • serine-type endopeptidase inhibitor activity • peptidase activity • peptide binding • metal ion binding • nerve growth factor binding Cellular component • Golgi membrane • extracellular space • endoplasmic reticulum membrane • Golgi apparatus • Golgi lumen • trans-Golgi network • plasma membrane • cell surface • integral to membrane • trans-Golgi network transport vesicle • Golgi cisterna • membrane raft Biological process • signal peptide processing • proteolysis • transforming growth factor beta receptor signaling pathway • Notch signaling pathway • aging • cell proliferation • protein processing • protein processing • peptide hormone processing • peptidyl-glutamic acid carboxylation • viral assembly, maturation, egress, and release • positive regulation of cell migration • positive regulation of transforming growth factor beta receptor signaling pathway • nerve growth factor processing • negative regulation of low-density lipoprotein particle receptor catabolic process • nerve growth factor production • negative regulation of nerve growth factor production • negative regulation of transforming growth factor beta1 production • secretion by cell • regulation of protein catabolic process • peptide biosynthetic process • post-translational protein modification • cellular protein metabolic process • nerve growth factor receptor signaling pathway • positive regulation of membrane protein ectodomain proteolysis • regulation of endopeptidase activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5045	18550
Ensembl	ENSG00000140564	ENSMUSG00000030530
UniProt	P09958	P23188
RefSeq (mRNA)	NM_002569.2	NM_001081454.1
RefSeq (protein)	NP_002560.1	NP_001074923.1
Location (UCSC)	Chr 15: 91.41 – 91.43 Mb	Chr 7: 87.53 – 87.55 Mb
PubMed search	[1]	[2]
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Furin is a protein that in humans is encoded by the FURIN gene.^[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).

Function[link]

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 also thought to be one of the proteases responsible for the proteolytic cleavage of HIV envelope polyprotein precursor gp160 to gp120 and gp41 prior to viral assembly. 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.^[7] 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.^[8]

Expression of furin in T-cells is required for maintenance of peripheral immune tolerance.^[9]

Interactions[link]

Furin has been shown to interact with PACS1.^[10]

References[link]

Further reading[link]

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v t e PDB gallery 1p8j: CRYSTAL STRUCTURE OF THE PROPROTEIN CONVERTASE FURIN