PAR4 is a G-protein-coupled receptor which can be activated by thrombin (factor IIa), plasmin, trypsin, and cathepsin G. It consists of 385 amino acids (41 kDa), including the amino-terminal signal sequence, and is widely expressed in various tissues. It is not expressed in the brain, kidney, spinal cord, and peripheral blood leukocytes. The gene maps to 19p2 (gene name: F2RL3).
PAR4 is activated by specific proteolysis at the site PAPR47 ↓ G48YPGQV to expose the tethered ligand GYPGKV which binds to the second extracellular loop, thus activating the receptor. A synthetic peptide (“activating peptide”) that mimics the tethered ligand domain (GYPGQV-NH2) directly binds to and activates PAR4 in vitro without proteolytic cleavage. PAR4 does not carry a hirudin-like binding site for thrombin as observed in PAR1 and PAR3. Thus, PAR4is a low-affinity receptor for thrombin. Despite this...