Furin is a membrane-associated, calcium-dependent serine protease that belongs to the subtilisin-like proprotein convertase (PC) family . This enzyme plays a crucial role in the proteolytic maturation of a wide variety of precursor proteins, including hormones, growth factors, receptors, and enzymes . Recombinant human furin is produced using various expression systems to study its function and potential therapeutic applications.
Furin is synthesized as an inactive zymogen and undergoes autocatalytic cleavage to become active . The active enzyme is composed of several domains, including a propeptide domain, a catalytic domain, a P-domain, and a transmembrane domain . The catalytic domain is responsible for the enzyme’s proteolytic activity, while the P-domain is involved in substrate recognition and binding .
Furin cleaves its substrates at specific sites, typically characterized by the sequence R-X-K/R-R, where X can be any amino acid . This cleavage is essential for the activation of many proproteins, including prohormones, neuropeptide precursors, viral proteins, and bacterial toxins .
Furin is ubiquitously expressed in various tissues and is involved in numerous physiological processes . In the brain, furin processes proproteins of growth factors, receptors, and enzymes, playing a vital role in neuronal survival, axon growth, dendritic development, synaptogenesis, and neurodegeneration . Aberrant activity of furin has been associated with a wide range of pathological events, including cancer, cardiovascular disorders, infectious diseases, and neurological diseases .
Recombinant human furin is produced using various expression systems, including mammalian cells, insect cells, and bacteria . The recombinant protein is typically purified to high purity and validated for its proteolytic activity . For example, recombinant human furin expressed in vaccinia virus-infected BSC-40 cells has been shown to have high proteolytic activity and purity .
Recombinant human furin is widely used in research to study its role in various biological processes and diseases . It is also used in the development of therapeutic interventions targeting furin activity. For instance, furin inhibitors are being explored as potential treatments for diseases where furin activity is dysregulated, such as cancer and viral infections .