Protease-activated receptor 2 (IPR002281)

Short name: Pro_rcpt_2

Overlapping homologous superfamilies


Family relationships


G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups [PMID: 12679517]. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [PMID: 8170923]. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [PMID: 8170923, PMID: 8081729, PMID: 15914470, PMID: 18948278, PMID: 16753280]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice [PMID: 12679517]. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [PMID: 23020293].

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [PMID: 2111655, PMID: 2830256, PMID: 8386361].

Several 7TM receptors have been cloned but their endogenous ligands are unknown; these have been termed orphan receptors. A GPCR similar to the receptor for the blood clotting enzyme thrombin has been cloned [PMID: 7890726]. Like the thrombin receptor, this receptor is activated by N-terminal proteolytic cleavage. Thus, because the physiological agonist at the receptor is unknown, it has been provisionally named proteinase-activated receptor 2 (PAR-2) [PMID: 7890726]. Human PAR-2 (hPAR-2) resides both on the plasma membrane and in the Golgi apparatus [PMID: 8615752]. hPAR-2 mRNA is highly expressed in human pancreas, kidney, colon, liver and small intestine, and by A549 lung and SW480 colon adenocarcinoma cells [PMID: 8615752]. Hybridisation in situ reveals high expression in intestinal epithelial cells throughout the gut [PMID: 8615752], where it is thought that PAR-2 may serve as a trypsin sensor [PMID: 8615752]. Its expression by cells and tissues not normally exposed to pancreatic trypsin suggests that other proteases could serve as physiological activators [PMID: 8615752].

GO terms

Biological Process

GO:0070493 thrombin-activated receptor signaling pathway

Molecular Function

GO:0015057 thrombin-activated receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.