Pr3

Proteinase 3 (PR3) is a neutrophil serine protease belonging to the chymotrypsin family. It is stored in azurophil granules and released during neutrophil degranulation in response to immune or inflammatory stimuli. PR3 is encoded by the PRTN3 gene in humans and has also been historically referred to as myeloblastin.

Biochemical properties and function: PR3 exhibits serine protease activity with a chymotrypsin-like catalytic mechanism. It cleaves a range of protein substrates and participates in antimicrobial defense by processing both microbial and host proteins. PR3 can modulate inflammatory signaling by processing cytokines and chemokines, and its activity is tightly regulated by endogenous inhibitors to limit tissue damage during immune responses.

Clinical significance: PR3 is a major antigen targeted by anti-neutrophil cytoplasmic antibodies (PR3-ANCA, commonly referred to as c-ANCA). PR3-ANCA are strongly associated with granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis) and are observed in other vasculitic disorders. Binding of PR3-ANCA to neutrophils can promote activation, degranulation, and reactive oxygen species production, contributing to vascular inflammation and tissue injury.

Diagnostics and research: Laboratory tests detect anti-PR3 antibodies and can measure PR3 activity, aiding diagnosis and monitoring of related diseases. PR3 continues to be a focus of research as a biomarker and as a potential therapeutic target for inflammatory and autoimmune conditions.