PCSK2 Gene: Proprotein Convertase Subtilisin/Kexin Type 2 | Function, Mutations & Diseases

PCSK2 encodes proprotein convertase 2 (PC2), a calcium-dependent serine endoprotease that processes precursor proteins into their active forms within the regulated secretory pathway. PC2 is primarily expressed in neuroendocrine tissues and is essential for the maturation of prohormones such as proinsulin, proglucagon, proopiomelanocortin (POMC), and proneuropeptide Y. The enzyme is synthesized as a zymogen and requires autocatalytic cleavage and binding to the chaperone 7B2 (SCG5) for activation. Dysregulation of PCSK2 has been implicated in metabolic disorders, neurodegenerative diseases, and cancer.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Proinsulin processing (Reactome: R-HSA-264876)

• POMC processing (Reactome: R-HSA-209776)

• Neuropeptide Y processing (Reactome: R-HSA-422085)

• Regulated exocytosis (Reactome: R-HSA-2980736)

Proprotein convertase 2 (PC2) is a 638-amino-acid serine protease with a catalytic domain characteristic of the subtilisin/kexin family. It is synthesized as a 75-kDa precursor that undergoes autocatalytic removal of an N-terminal propeptide to yield the active 68-kDa form. PC2 requires the neuroendocrine chaperone 7B2 for proper folding and transport from the Golgi to secretory granules. The enzyme cleaves at paired basic amino acid motifs (e.g., Lys-Arg, Arg-Arg) to activate prohormones and proneuropeptides. PC2 is highly expressed in the brain, pituitary, and pancreatic islets. Its activity is regulated by pH, calcium, and the inhibitory C-terminal fragment of 7B2.