Furin

Furin is a is_associated_with::protein that in humans is encoded by the FURIN is_associated_with::gene. Some proteins are inactive when they are first synthesized, and must have sections deleted in order to become active. Furin deletes these sections and activates the proteins. It was named furin because it was in the upstream region of an is_associated_with::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 ( P aired basic A mino acid C leaving E nzyme).

Function
The is_associated_with::protein encoded by this gene is an is_associated_with::enzyme which belongs to the is_associated_with::subtilisin-like is_associated_with::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: prois_associated_with::parathyroid hormone, transforming growth factor beta 1 precursor, prois_associated_with::albumin, pro-beta-secretase, membrane type-1 matrix metalloproteinase, beta subunit of pro-is_associated_with::nerve growth factor and is_associated_with::von Willebrand factor. A furin-like pro-protein convertase has been implicated in the processing of RGMc (also called is_associated_with::hemojuvelin), a gene involved in a severe iron-overload disorder called juvenile hemochromatosis. Both the Ganz and Rotwein groups demonstrated that furin-like is_associated_with::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.

Furin is one of the proteases responsible for the proteolytic cleavage of HIV envelope polyprotein precursor is_associated_with::gp160 to is_associated_with::gp120 and is_associated_with::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.

Furin is enriched in the is_associated_with::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 is_associated_with::HIV, influenza and is_associated_with::dengue fever viruses must be cleaved by furin or furin-like proteases to become fully functional. is_associated_with::Anthrax toxin, is_associated_with::pseudomonas is_associated_with::exotoxin, and is_associated_with::papillomaviruses must be processed by furin during their initial entry into host cells. Inhibitors of furin are under consideration as therapeutic agents for treating is_associated_with::anthrax infection.

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

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

Interactions
Furin has been shown to interact with is_associated_with::PACS1.