PRTN3 gene

The PRTN3 gene (PRTN3 stands for proteinase 3) is a protein-coding gene located on chromosome 19p13.3. The signaling pathways associated with this gene include the innate immune system and cytokine signaling in the immune system.

The PRTN3 gene encodes proteinase 3 which degrades elastin, fibronectin, laminin, vitronectin and collagen types I, III and IV (in vitro) (

Proteinase 3 is found in neutrophil granules and on the neutrophil extracellular membrane (mPR3). mPR3 is an important antigen for anti-neutrophil cytoplasmic antibodies (PR3-ANCAs), autoantibodies that cause various autoimmune diseases. autoimmune diseases. In most people, a subpopulation of neutrophils also produces CD177, which is thought to present additional PR3 on the surface, resulting in CD177neg/mPR3low and CD177pos/mPR3high neutrophil subpopulations. A positive correlation between mPR3 abundance, disease incidence and clinical outcome has been demonstrated (Rao NV et al. 1991;Jerke U et al. 2017;Kao RC et al. 1988).

By cleaving and activating the receptor F2RL1/PAR-2, it improves the barrier function of endothelial cells and thus vascular integrity during transendothelial migration of neutrophils (Rao NV et al. 1991). Plays a role in the transendothelial migration of neutrophils, probably in conjunction with CD177. Triggers inflammatory processes in neutrophils by interacting with ADGRG3 prior to activation of F2RL1/PAR2 (Chu TY et al. 2022)

Proteinase 3 is involved in several processes, including differentiation of mature conventional dendritic cells, extravasation of neutrophils and positive regulation of GTPase activity. Found in the lumen of azurophilic granules, in the cytosol and in plasma membrane rafts.

Diseases associated with PRTN3 include granulomatosis with polyangiitis and vasculitis.

Neutrophils play an important role in the body's defense against infections and inflammation. However, their activity must be strictly regulated, as malfunctions can often lead to harmful inflammation and autoimmune diseases. The adhesion molecule GPR97 allosterically activates the CD177-associated membrane protease 3 (mPR3), which in combination with several protein interaction partners leads to the activation of neutrophils in humans.

1. Chu TY et al. 2022) GPR97 triggers inflammatory processes in human neutrophils via a macromolecular complex upstream of PAR2 activation. Nat Commun 13:6385
2. Jerke U et al. (2017) Characterization of the CD177 interaction with the ANCA antigen proteinase 3. Sci Rep 7:43328.
3. Kao RC et al. (1988) Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters. J Clin Invest 82:1963-1973.
4. Rao NV et al. (1991) Characterization of proteinase-3 (PR-3), a neutrophil serine proteinase. Structural and functional properties. J Biol Chem 266:9540-9548.