Protease-activated receptor 3 (PAR3) (PAR3)

Protease-activated receptor 3 (PAR3) is a member of the G protein-coupled receptor family that is typically activated by thrombin-mediated cleavage of its extracellular N-terminus. In the context of innate immunity, fragments derived from this N-terminal region, known as P3 peptides, function as signaling molecules that modulate the activity of activated innate immune cells like macrophages and monocytes. These peptides are particularly noted for mimicking the anti-inflammatory and cytoprotective effects of Activated Protein C (APC) by interacting with other receptors such as PAR1. This interaction leads to the suppression of the NLRP3 inflammasome and a reduction in the production of pro-inflammatory cytokines. Consequently, the PAR3-derived P3 peptide and its analogs are being investigated as therapeutic targets for treating chronic inflammatory conditions, sepsis, and neurodegenerative diseases where innate immune overactivation plays a central role.

Other names

Coagulation factor II receptor-like 2F2RL2Thrombin receptor-like 2P3 peptideP3-51-65P3-42-65

The P3 peptide derived from PAR3 acts as an allosteric or orthosteric modulator that, often in conjunction with PAR1-derived peptides, mimics the cytoprotective and anti-inflammatory signaling of Activated Protein C (APC). It reduces caspase-1 activity and the release of pro-inflammatory cytokines like IL-1β in activated innate immune cells.