Furin (EC 220.127.116.11) is a highly specialized proteinase that cleaves the unique sequence motifs in a variety of proteins. Normally, following furin cleavage, the target protein is activated, and therefore, it can exhibit its biological activity. Because furin has been discovered first, currently, it is the most studied enzyme of the proprotein convertase (PC) family of serine proteinases. Seven distinct proprotein convertases of this family (furin, PC2, PC1/PC3, PC4, PACE4, PC5/PC6, and PC7) have been identified in humans, some of which have isoforms generated as the result of alternative splicing. Structurally and functionally, furin resembles its evolutionary precursor: the prohormone-processing enzyme, kexin (EC 18.104.22.168), which is encoded by the KEX2 gene of yeast Saccharomyces cerevisiae. The polypeptide sequence of the furin catalytic domain is...