PR01428

PROTEASEAR

PRINTS entry
Member databasePRINTS
PRINTS typefamily
Short namePROTEASEAR

Description
Imported from IPR003912

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
[10]
. 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
[6]
. 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)
[6, 13, 12, 11, 9]
. 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
[10]
. 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
[8]
.

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
[1, 5, 7]
.

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
[4]
. 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)
[2]
. 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
[3]
.

References
Imported from IPR003912

1.G proteins in signal transduction. Birnbaumer L. Annu. Rev. Pharmacol. Toxicol. 30, 675-705, (1990). View articlePMID: 2111655

2.The mouse proteinase-activated receptor-2 cDNA and gene. Molecular cloning and functional expression. Nystedt S, Larsson AK, Aberg H, Sundelin J. J. Biol. Chem. 270, 5950-55, (1995). View articlePMID: 7890726

3.Conserved structure and adjacent location of the thrombin receptor and protease-activated receptor 2 genes define a protease-activated receptor gene cluster. Kahn M, Ishii K, Kuo WL, Piper M, Connolly A, Shi YP, Wu R, Lin CC, Coughlin SR. Mol. Med. 2, 349-57, (1996). View articlePMID: 8784787

4.Protease-activated receptor 3 is a second thrombin receptor in humans. Ishihara H, Connolly AJ, Zeng D, Kahn ML, Zheng YW, Timmons C, Tram T, Coughlin SR. Nature 386, 502-6, (1997). View articlePMID: 9087410

5.G protein involvement in receptor-effector coupling. Casey PJ, Gilman AG. J. Biol. Chem. 263, 2577-80, (1988). View articlePMID: 2830256

6.Fingerprinting G-protein-coupled receptors. Attwood TK, Findlay JB. Protein Eng. 7, 195-203, (1994). View articlePMID: 8170923

7.Design of a discriminating fingerprint for G-protein-coupled receptors. Attwood TK, Findlay JB. Protein Eng. 6, 167-76, (1993). View articlePMID: 8386361

8.G protein-coupled receptor deorphanizations. Civelli O, Reinscheid RK, Zhang Y, Wang Z, Fredriksson R, Schioth HB. Annu. Rev. Pharmacol. Toxicol. 53, 127-46, (2013). PMID: 23020293

9.Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse. Bjarnadottir TK, Gloriam DE, Hellstrand SH, Kristiansson H, Fredriksson R, Schioth HB. Genomics 88, 263-73, (2006). View articlePMID: 16753280

10.The G protein-coupled receptor repertoires of human and mouse. Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, Brown A, Rodriguez SS, Weller JR, Wright AC, Bergmann JE, Gaitanaris GA. Proc. Natl. Acad. Sci. U.S.A. 100, 4903-8, (2003). View articlePMID: 12679517

11.IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. Harmar AJ, Hills RA, Rosser EM, Jones M, Buneman OP, Dunbar DR, Greenhill SD, Hale VA, Sharman JL, Bonner TI, Catterall WA, Davenport AP, Delagrange P, Dollery CT, Foord SM, Gutman GA, Laudet V, Neubig RR, Ohlstein EH, Olsen RW, Peters J, Pin JP, Ruffolo RR, Searls DB, Wright MW, Spedding M. Nucleic Acids Res. 37, D680-5, (2009). View articlePMID: 18948278

12.International Union of Pharmacology. XLVI. G protein-coupled receptor list. Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, Spedding M, Harmar AJ. Pharmacol. Rev. 57, 279-88, (2005). View articlePMID: 15914470

13.GCRDb: a G-protein-coupled receptor database. Kolakowski LF Jr. Recept. Channels 2, 1-7, (1994). PMID: 8081729

Supplementary References

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