Protease-activated receptor 2

215014063ENSG00000164251ENSMUSG00000021678P55085P55086NM_005242NM_007974NP_005233NP_032000Protease activated receptor 2 (PAR2) also known as coagulation factor II (thrombin) receptor-like 1 (F2RL1) or G-protein coupled receptor 11 (GPR11) is a protein that in humans is encoded by the F2RL1 gene. PAR2 modulates inflammatory responses, obesity, metabolism, and acts as a sensor for proteolytic enzymes generated during infection. Protease activated receptor 2 (PAR2) also known as coagulation factor II (thrombin) receptor-like 1 (F2RL1) or G-protein coupled receptor 11 (GPR11) is a protein that in humans is encoded by the F2RL1 gene. PAR2 modulates inflammatory responses, obesity, metabolism, and acts as a sensor for proteolytic enzymes generated during infection. The F2RL1 gene contains two exons and is widely expressed in human tissues. The predicted protein sequence is 83% identical to the mouse receptor sequence. PAR2 is a member of the large family of 7-transmembrane receptors that couple to guanosine-nucleotide-binding proteins. PAR2 is also a member of the protease-activated receptor family. It is activated by trypsin, but not by thrombin. It is activated by proteolytic cleavage of its extracellular amino terminus. The new amino terminus functions as a tethered ligand and activates the receptor. Additionally, these receptors can be activated by exogenous proteases, such as house dust mite protein Der P9. These receptors can also be activated non-protealytically, by exogenous peptide sequences that mimic the final amino acids of the tethered ligand. Potent and selective small molecule agonists and antagonists for PAR2 have been discovered. Functional selectivity occurs with PAR2, several proteases cleave PAR2 at distinct sites leading to biased signalling. Synthetic small ligands also modulate biased signalling leading to different functional responses. So far, PAR2 has been co-crystallized with two different antagonist ligands, while an agonist-bound state model of PAR2 (with the endogenous ligand SLIGKV) has been determined through mutagenesis and structure-based drug design. This article incorporates text from the United States National Library of Medicine, which is in the public domain.