Furin Antibody #43996

The proprotein convertases (PCs) are enzymes that activate precursor proteins through proteolytic cleavage within the secretory pathway. PCs comprise several enzymes that are basic amino acid-specific proteinases (furin, PC1/3, PC2, PC4, PACE4, PC5/6, and PC7), as well as nonbasic amino acid convertases (S1P and PC9) (1). PCs have a common structure that includes an N-terminal signal peptide for secretory pathway targeting; a pro-domain that is thought to act as an intramolecular chaperone; a catalytic domain containing the active site; a P-domain that contributes to the overall folding of the enzyme by regulating stability and both calcium- and pH-dependence; and a C-terminal domain that interacts with the membrane (2). PCs act in a tissue- and substrate-specific fashion to generate an array of bioactive peptides and proteins from precursors, both in the brain and in peripheral tissues (3). The SARS-CoV-2 coronavirus contains an inactive precursor spike glycoprotein, with a distinct furin cleavage site at the S1/S2 domain junction. Cleavage by furin "primes" the spike protein for binding to the ACE2 receptor and subsequent viral entry to the host cell (4-6). Loss of the furin cleavage site has been shown to drastically reduce the virulence of the SARS-CoV-2 virus (6-8). Furin cleavage sites are seen in a variety of other viral pathogens as well, including other CoV family members, HIV, avian influenza strains, and Ebola (6,8). In addition, furin has been proposed as a therapeutic target in cancer, and in regard to NMDA receptor-associated pathologies in the brain (9,10).