PRTN3

PRTN3 Full Name

Proteinase 3

PRTN3 Introduction

Proteinase 3 (PRTN3) is a neutrophil serine protease. Proteinase 3 is synthesized as a preproenzyme that is stored in azurophilic granules and is secreted following neutrophilic inflammatory activation. Upon processing, it becomes a mature, active neutrophil protease capable of degrading diverse extracellular matrix components, antimicrobial peptides and other cell-surface molecules. PRTN3 is primarily expressed in neutrophils. It is important for host innate immune responses, in which it is a key mediator of microbial killing and regulation of inflammatory signaling. The activity of PRTN3 is regulated by endogenous inhibitors to limit host tissue damage during inflammatory defense.

Figure 1. Summary of the actions of Proteinase 3 (PR3).(Source: Crisford H, et al.; 2018)

Functionally, PRTN3 is involved in NET formation, cytokine processing, and regulation of leukocyte migration. It alters the activation and cleavage of IL-32, elastin, and various chemokines, in order to influence both local and systemic inflammatory processes. In addition to having direct antimicrobial activity, PRTN3 is also involved in the regulation of apoptosis and neutrophil turnover, to coordinate resolution of inflammation. It is a cell-surface molecule that as an adhesion and signaling protein, allows neutrophils to talk to endothelial cells and immune receptors during stress or infection.

In the clinic, dysregulation/abnormal expression/activity of PRTN3 has been linked to various diseases. The best characterized evidence is for PRTN3 as the autoantigen recognized by anti-neutrophil cytoplasmic antibodies (PR3-ANCA). In granulomatous polyangiitis, the autoimmune targeting of PRTN3 by PR3-ANCAs results in the small vessel vasculitis, endothelial damage, and organ damage. PRTN3 overexpression has also been implicated in chronic inflammatory disorders such as chronic obstructive pulmonary disease and cystic fibrosis.

Alternate Names for PRTN3

PRTN3; proteinase 3; myeloblastin; ACPA; AGP7; C ANCA; MBT; P29; PR 3; serine proteinase; neutrophil; Wegener granulomatosis autoantigen; NP-4; C-ANCA antigen; wegener autoantigen; leukocyte proteinase 3; neutrophil proteinase 4; azurophil granule protein

• Crisford H, et al.; Proteinase 3; a potential target in chronic obstructive pulmonary disease and other chronic inflammatory diseases. Respir Res. 2018, 19(1):180.