PAR3 is a G protein-coupled receptor which can be activated by thrombin (factor IIa). It consists of 374 amino acids (42 kDa) including the amino-terminal signal sequence and is highly expressed in megakaryocytes of the bone marrow. A lower expression is found in mature megakaryocytes, platelets, the heart, and the gut. The gene maps to 5q13.3 (gene name: F2RL2).
PAR3 is activated by specific proteolysis at the site LPIK38 ↓ T39FRGAP to expose the tethered ligand LPIK which binds to the second extracellular loop, thus activating the receptor. No synthetic peptides exist which are able to stimulate PAR3 in vitro, as observed with the other members of this receptor family. Distal to the thrombin cleavage site, there is a hirudin-like binding site located. This enables binding and concentration of thrombin at the cell surface, rendering PAR3a high-affinity receptor for thrombin....