Family

Protease-activated receptor (IPR003912)

Short name: Protea_act_rcpt

Family relationships

Description

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].

Thrombin is a coagulation protease that activates platelets, leukocytes, endothelial and mesenchymal cells at sites of vascular injury, acting partly through an unusual proteolytically activated GPCR [PMID: 9087410]. Gene knockout experiments have provided definitive evidence for a second thrombin receptor in mouse platelets and have suggested tissue-specific roles for different thrombin receptors. Because the physiological agonist at the receptor was originally unknown, it was provisionally named protease-activated receptor (PAR) [PMID: 7890726]. At least 4 PAR subtypes have now been characterised. Thus, the thrombin and PAR receptors constitute a fledgling receptor family that shares a novel proteolytic activation mechanism [PMID: 8784787].

GO terms

Biological Process

GO:0007596 blood coagulation
GO:0070493 thrombin receptor signaling pathway

Molecular Function

GO:0015057 thrombin receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

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