furin

Furin, officially proprotein convertase subtilisin/kexin type-3 (PCSK3), is a calcium-dependent serine protease in the subtilisin-like proprotein convertase (PCSK) family. It is encoded by the PCSK3 gene in humans.

Furin cleaves precursor proteins at multibasic motifs, most commonly R-X-(K/R)-R, to produce mature, active proteins. It is synthesized as an inactive zymogen and becomes active after autoproteolytic processing within the secretory pathway.

Furin localizes mainly to the trans-Golgi network, but is also found at the cell surface and in endosomes and secretory vesicles. Its activity is calcium-dependent and influenced by pH and subcellular localization.

The enzyme has a broad range of substrates, including prohormones, growth factors, receptors, and proteases, as well as viral envelope glycoproteins. This broad substrate specificity makes furin an important mediator of normal physiology and a factor in several diseases, including infectious diseases and cancer.

Functional importance is underscored by embryonic lethality in mice lacking PCSK3, indicating furin’s essential role in development. Dysregulation of furin activity has been linked to cancer, infectious diseases, and inflammatory processes. Because many pathogens depend on furin for processing, furin inhibitors are explored as potential therapeutic agents.