Thrombin receptor (IPR000935)

Short name: Thrmbn_rcpt

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].

Thrombin is a serine protease with a central role in blood clotting. It cleaves various substrates involved in coagulation, and activates cell surface receptors via a novel proteolytic action. Thrombin stimulates aggregation and secretion in blood platelets at the site of vascular injury, and also has inflammatory and reparative actions, stimulating chemotaxis in monocytes, proliferation of fibroblasts and lymphocytes, and inducing endothelium-dependent relaxation of blood vessels. The protein activates a number of substrates involved in coagulation: it cleaves fibrinogen to fibrin and activates coagulation factor XIII; it also activates factors V and VIII. When bound to thrombomodulin, it activates plasma protein C, which, in concert with protein S, inactivates factors Va and VIIIa, leading to a decrease in thrombin formation.

The thrombin receptor is expressed in high levels in platelets, vascular endothelial cells, and various cell lines. The receptor activates phosphoinositide metabolism via a pertussis-toxin-insensitive G-protein, and inhibits adenylyl cyclase via a pertussis-toxin-sensitive G-protein.

GO terms

Biological Process

GO:0007186 G-protein coupled receptor signaling pathway
GO:0007596 blood coagulation

Molecular Function

GO:0004930 G-protein coupled receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

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