Coagulation factor II receptor-like 2 (PAR3) (PAR3)

Coagulation factor II receptor-like 2, commonly known as Protease-activated receptor 3 (PAR3), is a member of the G protein-coupled receptor (GPCR) family that plays a specialized role in the regulation of blood coagulation and inflammatory responses [2, 8]. Unlike traditional receptors, PAR3 is activated through the proteolytic cleavage of its extracellular N-terminus by serine proteases, most notably thrombin, which exposes a tethered ligand that binds to the receptor's own extracellular loops [2, 4]. In humans, PAR3 is primarily recognized as a cofactor that facilitates the activation of PAR4 by thrombin, particularly on the surface of platelets and endothelial cells, although it has also been shown to signal autonomously in certain cell types like neurons and epithelial cells [5, 13]. Beyond its role in hemostasis and thrombosis, PAR3 is implicated in various pathological processes, including chronic inflammation, nociception (pain sensing), and the progression of certain cancers such as renal cell carcinoma and pancreatic adenocarcinoma [4, 6, 13]. While there are currently no FDA-approved drugs specifically targeting PAR3, it remains a target of significant interest for the development of novel antithrombotic and anti-inflammatory therapies [11, 17]. Experimental modulators, including selective peptide agonists like C660 and antisense oligonucleotides, are being utilized in research to further elucidate its therapeutic potential and its complex interactions with other members of the PAR family [4, 6, 17].

Other names

F2RL2Protease-activated receptor 3Proteinase-activated receptor 3Thrombin receptor-like 2PAR-3

Proteolytic cleavage of the N-terminal extracellular domain by serine proteases (e.g., thrombin) exposes a tethered ligand that binds to the receptor's second extracellular loop, triggering G-protein-mediated signaling and acting as a cofactor for the activation of other protease-activated receptors like PAR4.