F2RL3

Coagulation factor II (thrombin) receptor-like 3
Identifiers
Symbols	F2RL3; PAR4
External IDs	OMIM: 602779 MGI: 1298207 HomoloGene: 36148 IUPHAR: PAR4 GeneCards: F2RL3 Gene
Gene Ontology Molecular function • receptor activity • G-protein coupled receptor activity • thrombin receptor activity Cellular component • extracellular region • plasma membrane • plasma membrane • integral to plasma membrane Biological process • signal transduction • G-protein coupled receptor protein signaling pathway • activation of phospholipase C activity by G-protein coupled receptor protein signaling pathway coupled to IP3 second messenger • blood coagulation • response to wounding • platelet activation • positive regulation of release of sequestered calcium ion into cytosol • platelet dense granule organization • thrombin receptor signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9002	14065
Ensembl	ENSG00000127533	ENSMUSG00000050147
UniProt	Q96RI0	Q0VDX1
RefSeq (mRNA)	NM_003950	NM_007975.3
RefSeq (protein)	NP_003941	NP_032001.2
Location (UCSC)	Chr 19: 17 – 17 Mb	Chr 8: 75.29 – 75.29 Mb
PubMed search	[1]	[2]

Protease-activated receptor 4 (PAR4), previously known as Coagulation factor II (thrombin) receptor-like 3, is a protein encoded by the F2RL3 gene in humans.^[1]

Coagulation factor II (thrombin) receptor-like 3 (F2RL3) is a member of the large family of 7-transmembrane-region receptors that couple to guanosine-nucleotide-binding proteins. F2RL3 is also a member of the protease-activated receptor family. F2RL3 is activated by proteolytic cleavage of its extracellular amino terminus. The new amino terminus functions as a tethered ligand and activates the receptor. F2RL3 is activated by thrombin and trypsin.^[1]

See also

• Protease-activated receptor

References

1. ^ ^{a b} "Entrez Gene: F2RL3 coagulation factor II (thrombin) receptor-like 3". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9002. 

External links

• "Protease-Activated Receptors: PAR4". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3036. 

Further reading

• Leger AJ, Covic L, Kuliopulos A (2006). "Protease-activated receptors in cardiovascular diseases.". Circulation 114 (10): 1070–7. doi:10.1161/CIRCULATIONAHA.105.574830. PMID 16952995. 
• Xu WF, Andersen H, Whitmore TE, et al. (1998). "Cloning and characterization of human protease-activated receptor 4.". Proc. Natl. Acad. Sci. U.S.A. 95 (12): 6642–6. doi:10.1073/pnas.95.12.6642. PMC 22580. PMID 9618465. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=22580. 
• Kahn ML, Zheng YW, Huang W, et al. (1998). "A dual thrombin receptor system for platelet activation.". Nature 394 (6694): 690–4. doi:10.1038/29325. PMID 9716134. 
• Kahn ML, Hammes SR, Botka C, Coughlin SR (1998). "Gene and locus structure and chromosomal localization of the protease-activated receptor gene family.". J. Biol. Chem. 273 (36): 23290–6. doi:10.1074/jbc.273.36.23290. PMID 9722561. 
• Kahn ML, Nakanishi-Matsui M, Shapiro MJ, et al. (1999). "Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin.". J. Clin. Invest. 103 (6): 879–87. doi:10.1172/JCI6042. PMC 408153. PMID 10079109. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=408153. 
• Andersen H, Greenberg DL, Fujikawa K, et al. (1999). "Protease-activated receptor 1 is the primary mediator of thrombin-stimulated platelet procoagulant activity.". Proc. Natl. Acad. Sci. U.S.A. 96 (20): 11189–93. doi:10.1073/pnas.96.20.11189. PMC 18009. PMID 10500152. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=18009. 
• Sambrano GR, Huang W, Faruqi T, et al. (2000). "Cathepsin G activates protease-activated receptor-4 in human platelets.". J. Biol. Chem. 275 (10): 6819–23. doi:10.1074/jbc.275.10.6819. PMID 10702240. 
• Nakanishi-Matsui M, Zheng YW, Sulciner DJ, et al. (2000). "PAR3 is a cofactor for PAR4 activation by thrombin.". Nature 404 (6778): 609–13. doi:10.1038/35007085. PMID 10766244. 
• Miike S, McWilliam AS, Kita H (2002). "Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2.". J. Immunol. 167 (11): 6615–22. PMID 11714832. 
• Asokananthan N, Graham PT, Fink J, et al. (2002). "Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells.". J. Immunol. 168 (7): 3577–85. PMID 11907122. 
• Henriksen RA, Hanks VK (2002). "PAR-4 agonist AYPGKF stimulates thromboxane production by human platelets.". Arterioscler. Thromb. Vasc. Biol. 22 (5): 861–6. doi:10.1161/01.ATV.0000014742.56572.25. PMID 12006403. 
• Covic L, Singh C, Smith H, Kuliopulos A (2003). "Role of the PAR4 thrombin receptor in stabilizing platelet-platelet aggregates as revealed by a patient with Hermansky-Pudlak syndrome.". Thromb. Haemost. 87 (4): 722–7. PMID 12008957. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Owen WG (2003). "PAR-3 is a low-affinity substrate, high affinity effector of thrombin.". Biochem. Biophys. Res. Commun. 305 (1): 166–8. doi:10.1016/S0006-291X(03)00732-0. PMID 12732212. 
• Adam F, Verbeuren TJ, Fauchère JL, et al. (2003). "Thrombin-induced platelet PAR4 activation: role of glycoprotein Ib and ADP.". J. Thromb. Haemost. 1 (4): 798–804. doi:10.1046/j.1538-7836.2003.00138.x. PMID 12871418. 
• Wu CC, Hwang TL, Liao CH, et al. (2004). "The role of PAR4 in thrombin-induced thromboxane production in human platelets.". Thromb. Haemost. 90 (2): 299–308. doi:10.1267/THRO03020299. PMID 12888878. 
• Kawai T, Akira S, Reed JC (2003). "ZIP kinase triggers apoptosis from nuclear PML oncogenic domains.". Mol. Cell. Biol. 23 (17): 6174–86. doi:10.1128/MCB.23.17.6174-6186.2003. PMC 180930. PMID 12917339. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=180930. 
• Jacques SL, Kuliopulos A (2004). "Protease-activated receptor-4 uses dual prolines and an anionic retention motif for thrombin recognition and cleavage.". Biochem. J. 376 (Pt 3): 733–40. doi:10.1042/BJ20030954. PMC 1223816. PMID 13678420. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1223816. 
• Han Y, Nurden A, Combrié R, Pasquet JM (2004). "Redistribution of glycoprotein Ib within platelets in response to protease-activated receptors 1 and 4: roles of cytoskeleton and calcium.". J. Thromb. Haemost. 1 (10): 2206–15. doi:10.1046/j.1538-7836.2003.00436.x. PMID 14521606. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Metabolites and
signaling molecules

Eicosanoid	CysLT (1, 2) · LTB4 (1, 2) · FPRL1 · OXE · Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) · Prostacyclin · Thromboxane
Other	Bile acid · Cannabinoid (CB1, CB2, GPR (18, 55, 119)) · EBI2 · Estrogen · Free fatty acid (1, 2, 3, 4) · Lactate  · Lysophosphatidic acid (1, 2, 3, 4, 5, 6)  · Lysophospholipid (1, 2, 3, 4, 5, 6, 7, 8) · Niacin (1, 2) · Oxoglutarate · PAF · Sphingosine-1-phosphate (1, 2, 3, 4, 5) · Succinate

Peptide

Neuropeptide	B/W (1, 2) · FF (1, 2) · S · Y (1, 2, 4, 5) · Neuromedin (B, U (1, 2)) · Neurotensin (1, 2)
Other	Anaphylatoxin (C3a, C5a) · Angiotensin (1, 2) · Apelin · Bombesin (BRS3, GRPR, NMBR) · Bradykinin (B1, B2) · Chemokine · Cholecystokinin (A, B) · Endothelin (A, B) · Formyl peptide (1, 2, 3) · FSH · Galanin (1, 2, 3) · GHB receptor · Gonadotropin-releasing hormone (1, 2) · Ghrelin · Kisspeptin · Luteinizing hormone/choriogonadotropin · MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) · Melanocortin (1, 2, 3, 4, 5) · MCHR (1, 2) · Motilin · Opioid (Delta, Kappa, Mu, Nociceptin & Zeta, but not Sigma) · Orexin (1, 2) · Oxytocin · Prokineticin (1, 2) · Prolactin-releasing peptide · Relaxin (1, 2, 3, 4) · Somatostatin (1, 2, 3, 4, 5) · Tachykinin (1, 2, 3) · Thyrotropin · Thyrotropin-releasing hormone · Urotensin-II · Vasopressin (1A, 1B, 2)

Miscellaneous

Orphan	GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Other	Adrenomedullin · Olfactory · Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) · Protease-activated (1, 2, 3, 4) · SREB (1, 2, 3)

Class B: Secretin like

Orphan	GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Other	Brain-specific angiogenesis inhibitor (1, 2, 3) · Cadherin (1, 2, 3) · Calcitonin · CALCRL · CD97 · Corticotropin-releasing hormone (1, 2) · EMR (1, 2, 3) · Glucagon (GR, GIPR, GLP1R, GLP2R) · Growth hormone releasing hormone · PACAPR1 · GPR · Latrophilin (1, 2, 3, ELTD1) · Methuselah-like proteins · Parathyroid hormone (1, 2) · Secretin · Vasoactive intestinal peptide (1, 2)

Class C: Metabotropic
glutamate / pheromone

Taste	TAS1R (1, 2, 3) · TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Other	Calcium-sensing receptor · GABA B (1, 2) · Glutamate receptor (Metabotropic glutamate (1, 2, 3, 4, 5, 6, 7, 8)) · GPRC6A · GPR (156, 158, 179) · RAIG (1, 2, 3, 4)

Class F:
Frizzled / Smoothened

Frizzled	Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Smoothened	Smoothened

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)