PAR3, also known as F2RL2 and Coagulation Factor II (Thrombin) Receptor-like 2, is a member of the Protease-activated Receptor (PAR) family of seven transmembrane G protein-coupled receptors that are activated by proteolysis. It is 374 amino acids (aa) in length with a predicted molecular weight of 42.5 kDa. Human PAR3 shares 72% aa sequence identity with the mouse and rat orthologs. PAR3 is highly expressed in the megakaryocytes of the bone marrow. It is also expressed, but in lower levels, in mature megakaryocytes, vascular endothelial and smooth muscle cells, platelets, and in a variety of other tissues such as heart and small intestines. PAR3 plays an essential role in hemostasis and thrombosis. Thrombin, a coagulation protease that activates platelets, binds to and cleaves the N-terminal extracellular domain of PAR3 to generate a new N-terminus. This new N-terminus then functions as a tethered peptide ligand that binds to the receptor. Interestingly, it appears the PAR3 is unable to mediate signaling responses to Thrombin. Instead, it seems to act as a cofactor for two other PAR family members, PAR1 and PAR4.