Proteinase-activated receptor 1

"F2R" redirects here. For the Navy fighter, see Ryan XF2R Dark Shark.

F2R
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1NRN, 1NRO, 1NRP, 1NRQ, 1NRR, 3BEF, 3HKI, 3HKJ, 3LU9, 3VW7
Identifiers
Aliases	F2R, CHTR, PAR-1, PAR1, TR, Coagulation factor II receptor, coagulation factor II thrombin receptor
External IDs	OMIM: 187930; MGI: 101802; HomoloGene: 1510; GeneCards: F2R; OMA:F2R - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q13.3 Start 76,716,126 bp End 76,735,770 bp
Gene location (Mouse) Chr. Chromosome 13 (mouse) Band 13 D1|13 50.21 cM Start 95,738,311 bp End 95,754,995 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium ventricular zone decidua ganglionic eminence right lung gallbladder skin of hip right coronary artery lower lobe of lung Descending thoracic aorta Top expressed in molar gastrula renal corpuscle endothelial cell of lymphatic vessel epithelium of lens external carotid artery internal carotid artery ciliary body decidua conjunctival fornix More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity signal transducer activity thrombin-activated receptor activity G-protein beta-subunit binding protein binding G-protein alpha-subunit binding signaling receptor binding Cellular component integral component of membrane platelet dense tubular network late endosome Golgi apparatus postsynaptic membrane membrane neuromuscular junction plasma membrane integral component of plasma membrane extracellular region cell surface early endosome caveola Biological process negative regulation of neuron apoptotic process positive regulation of collagen biosynthetic process hemostasis establishment of synaptic specificity at neuromuscular junction release of sequestered calcium ion into cytosol platelet dense granule organization regulation of sensory perception of pain thrombin-activated receptor signaling pathway positive regulation of cell migration positive regulation of cytosolic calcium ion concentration anatomical structure morphogenesis blood coagulation positive regulation of release of sequestered calcium ion into cytosol platelet activation phospholipase C-activating G protein-coupled receptor signaling pathway positive regulation of cysteine-type endopeptidase activity involved in apoptotic process response to lipopolysaccharide positive regulation of transcription, DNA-templated protein kinase C-activating G protein-coupled receptor signaling pathway positive regulation of blood coagulation response to wounding positive regulation of vasoconstriction positive regulation of cell population proliferation connective tissue replacement involved in inflammatory response wound healing positive regulation of ERK1 and ERK2 cascade regulation of interleukin-1 beta production positive regulation of I-kappaB kinase/NF-kappaB signaling homeostasis of number of cells within a tissue positive regulation of phosphatidylinositol 3-kinase signaling regulation of blood coagulation inflammatory response negative regulation of glomerular filtration activation of cysteine-type endopeptidase activity involved in apoptotic process positive regulation of smooth muscle contraction positive regulation of MAPK cascade negative regulation of cell population proliferation negative regulation of renin secretion into blood stream signal transduction positive regulation of calcium ion transport positive regulation of Rho protein signal transduction positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway trans-synaptic signaling by endocannabinoid, modulating synaptic transmission positive regulation of GTPase activity cell-cell junction maintenance G protein-coupled receptor signaling pathway positive regulation of receptor signaling pathway via JAK-STAT Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2149 14062 Ensembl ENSG00000181104 ENSMUSG00000048376 UniProt P25116 P30558 RefSeq (mRNA) NM_001992 NM_001311313 NM_010169 RefSeq (protein) NP_001298242 NP_001983 NP_034299 Location (UCSC) Chr 5: 76.72 – 76.74 Mb Chr 13: 95.74 – 95.75 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Proteinase-activated receptor 1 (PAR1) also known as Protease-activated receptor 1 or coagulation factor II (thrombin) receptor is a protein that in humans is encoded by the F2R gene. PAR1 is a G protein-coupled receptor involved in the regulation of thrombotic response. Proteolytic cleavage leads to the activation of the receptor.

PAR-1 has multifaceted effects and plays a key role in mediating the interplay between coagulation and inflammation, which is important in the pathogenesis of inflammatory and fibrotic lung diseases. It is involved both in disruption and maintaining of endothelial barrier integrity, through interaction with either thrombin or activated protein C, respectively.

Ligands

Several selective antagonists for the PAR1 receptor have been developed, for use as anti-clotting agents for the treatment of heart disease.

• SCH-530,348

SCH530348 has been recently shown to attenuate the neutrophilic inflammatory response to Streptococcus pneumoniae by reducing levels of pro-inflamamtory cytokines such as IL-1β and chemokines CXCL1, CCL2 and CCL7.

See also

• Protease-activated receptor

Further reading

• Coughlin SR, Vu TK, Hung DT, Wheaton VI (Feb 1992). "Characterization of a functional thrombin receptor. Issues and opportunities". The Journal of Clinical Investigation. 89 (2): 351–5. doi:10.1172/JCI115592. PMC 442859. PMID 1310691.
• Wu H, Zhang Z, Li Y, Zhao R, Li H, Song Y, Qi J, Wang J (Oct 2010). "Time course of upregulation of inflammatory mediators in the hemorrhagic brain in rats: correlation with brain edema". Neurochemistry International. 57 (3): 248–53. doi:10.1016/j.neuint.2010.06.002. PMID 20541575.
• Howell DC, Laurent GJ, Chambers RC (Apr 2002). "Role of thrombin and its major cellular receptor, protease-activated receptor-1, in pulmonary fibrosis". Biochemical Society Transactions. 30 (2): 211–6. doi:10.1042/BST0300211. PMID 12023853.
• Tellez C, Bar-Eli M (May 2003). "Role and regulation of the thrombin receptor (PAR-1) in human melanoma". Oncogene. 22 (20): 3130–7. doi:10.1038/sj.onc.1206453. PMID 12789289.
• Remillard CV, Yuan JX (May 2005). "PGE2 and PAR-1 in pulmonary fibrosis: a case of biting the hand that feeds you?". American Journal of Physiology. Lung Cellular and Molecular Physiology. 288 (5): L789-92. doi:10.1152/ajplung.00016.2005. PMID 15821019.
• Leger AJ, Covic L, Kuliopulos A (Sep 2006). "Protease-activated receptors in cardiovascular diseases". Circulation. 114 (10): 1070–7. doi:10.1161/CIRCULATIONAHA.105.574830. PMID 16952995.
• Traynelis SF, Trejo J (May 2007). "Protease-activated receptor signaling: new roles and regulatory mechanisms". Current Opinion in Hematology. 14 (3): 230–5. doi:10.1097/MOH.0b013e3280dce568. PMID 17414212.
• Vu TK, Hung DT, Wheaton VI, Coughlin SR (Mar 1991). "Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation". Cell. 64 (6): 1057–68. doi:10.1016/0092-8674(91)90261-V. PMID 1672265.
• Wojtukiewicz MZ, Tang DG, Ben-Josef E, Renaud C, Walz DA, Honn KV (Feb 1995). "Solid tumor cells express functional "tethered ligand" thrombin receptor". Cancer Research. 55 (3): 698–704. PMID 7834643.
• Hein L, Ishii K, Coughlin SR, Kobilka BK (Nov 1994). "Intracellular targeting and trafficking of thrombin receptors. A novel mechanism for resensitization of a G protein-coupled receptor". The Journal of Biological Chemistry. 269 (44): 27719–26. PMID 7961693.
• Mathews II, Padmanabhan KP, Ganesh V, Tulinsky A, Ishii M, Chen J, Turck CW, Coughlin SR, Fenton JW (Mar 1994). "Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and novel binding modes". Biochemistry. 33 (11): 3266–79. doi:10.1021/bi00177a018. PMID 8136362.
• Offermanns S, Laugwitz KL, Spicher K, Schultz G (Jan 1994). "G proteins of the G12 family are activated via thromboxane A2 and thrombin receptors in human platelets". Proceedings of the National Academy of Sciences of the United States of America. 91 (2): 504–8. doi:10.1073/pnas.91.2.504. PMC 42977. PMID 8290554.
• Hoffman M, Church FC (Aug 1993). "Response of blood leukocytes to thrombin receptor peptides". Journal of Leukocyte Biology. 54 (2): 145–51. PMID 8395550.
• Schmidt VA, Vitale E, Bahou WF (Apr 1996). "Genomic cloning and characterization of the human thrombin receptor gene. Structural similarity to the proteinase activated receptor-2 gene". The Journal of Biological Chemistry. 271 (16): 9307–12. doi:10.1074/jbc.271.16.9809. PMID 8621593.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Li F, Baykal D, Horaist C, Yan CN, Carr BN, Rao GN, Runge MS (Oct 1996). "Cloning and identification of regulatory sequences of the human thrombin receptor gene". The Journal of Biological Chemistry. 271 (42): 26320–8. doi:10.1074/jbc.271.42.26320. PMID 8824285.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Shapiro MJ, Trejo J, Zeng D, Coughlin SR (Dec 1996). "Role of the thrombin receptor's cytoplasmic tail in intracellular trafficking. Distinct determinants for agonist-triggered versus tonic internalization and intracellular localization". The Journal of Biological Chemistry. 271 (51): 32874–80. doi:10.1074/jbc.271.51.32874. PMID 8955127.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Ogino Y, Tanaka K, Shimizu N (Nov 1996). "Direct evidence for two distinct G proteins coupling with thrombin receptors in human neuroblastoma SH-EP cells". European Journal of Pharmacology. 316 (1): 105–9. doi:10.1016/S0014-2999(96)00653-X. PMID 8982657.
• Molino M, Bainton DF, Hoxie JA, Coughlin SR, Brass LF (Feb 1997). "Thrombin receptors on human platelets. Initial localization and subsequent redistribution during platelet activation". The Journal of Biological Chemistry. 272 (9): 6011–7. doi:10.1074/jbc.272.9.6011. PMID 9038223.{{cite journal}}: CS1 maint: unflagged free DOI (link)
• Renesto P, Si-Tahar M, Moniatte M, Balloy V, Van Dorsselaer A, Pidard D, Chignard M (Mar 1997). "Specific inhibition of thrombin-induced cell activation by the neutrophil proteinases elastase, cathepsin G, and proteinase 3: evidence for distinct cleavage sites within the aminoterminal domain of the thrombin receptor". Blood. 89 (6): 1944–53. PMID 9058715.

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