Coagulation factor II receptor

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

Coagulation factor II (thrombin) receptor

Rendering of F2R from PDB 1NRN

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1NRN, 1NRO, 1NRP, 1NRQ, 1NRR, 3BEF, 3HKI, 3HKJ, 3LU9, 3VW7

Identifiers

Symbols

F2R ; CF2R; HTR; PAR-1; PAR1; TR

External IDs

OMIM: 187930 MGI: 101802 HomoloGene: 1510 IUPHAR: 347 ChEMBL: 3974 GeneCards: F2R Gene

Gene ontology
Molecular function	• G-protein alpha-subunit binding • G-protein coupled receptor activity • receptor binding • protein binding • thrombin receptor activity • G-protein beta-subunit binding
Cellular component	• extracellular region • early endosome • late endosome • Golgi apparatus • cytosol • plasma membrane • integral component of plasma membrane • caveola • cell surface • platelet dense tubular network • neuromuscular junction • postsynaptic membrane
Biological process	• activation of MAPKK activity • connective tissue replacement involved in inflammatory response wound healing • negative regulation of glomerular filtration • activation of cysteine-type endopeptidase activity involved in apoptotic process • inflammatory response • G-protein coupled receptor signaling pathway • phospholipase C-activating G-protein coupled receptor signaling pathway • positive regulation of cytosolic calcium ion concentration • protein kinase C-activating G-protein coupled receptor signaling pathway • tyrosine phosphorylation of STAT protein • STAT protein import into nucleus • establishment of synaptic specificity at neuromuscular junction • blood coagulation • positive regulation of cell proliferation • negative regulation of cell proliferation • response to wounding • anatomical structure morphogenesis • positive regulation of phosphatidylinositol 3-kinase signaling • platelet activation • regulation of blood coagulation • positive regulation of blood coagulation • positive regulation of cell migration • response to lipopolysaccharide • regulation of interleukin-1 beta production • positive regulation of collagen biosynthetic process • positive regulation of Rho protein signal transduction • positive regulation of I-kappaB kinase/NF-kappaB signaling • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • positive regulation of MAPK cascade • negative regulation of neuron apoptotic process • positive regulation of transcription, DNA-templated • positive regulation of vasoconstriction • positive regulation of smooth muscle contraction • positive regulation of JAK-STAT cascade • homeostasis of number of cells within a tissue • release of sequestered calcium ion into cytosol • positive regulation of release of sequestered calcium ion into cytosol • positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway • positive regulation of calcium ion transport • regulation of sensory perception of pain • platelet dense granule organization • positive regulation of ERK1 and ERK2 cascade • thrombin receptor signaling pathway • negative regulation of renin secretion into blood stream • positive regulation of interleukin-8 secretion • positive regulation of interleukin-6 secretion
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 5:
76.72 – 76.74 Mb

Chr 13:
95.6 – 95.62 Mb

PubMed search

Proteinase-activated receptor 1 (PAR1) also known as the coagulation factor II (thrombin) receptor is a protein that in humans is encoded by the F2R gene.^[1] PAR1 is a G protein-coupled receptor involved in the regulation of thrombotic response. Proteolytic cleavage leads to the activation of the receptor.^[2] 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.^[3]

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.^[4]

References

↑ Bahou WF, Nierman WC, Durkin AS, Potter CL, Demetrick DJ (Sep 1993). "Chromosomal assignment of the human thrombin receptor gene: localization to region q13 of chromosome 5". Blood 82 (5): 1532–7. PMID 8395910.
↑ "Entrez Gene: F2R coagulation factor II (thrombin) receptor".
↑ "José RJ, Williams AE, Chambers RC (Feb 2014). "Proteinase-activated receptors in fibroproliferative lung disease". Thorax 69 (2): 190–2. doi:10.1136/thoraxjnl-2013-204367. PMID 24186921.
↑ José RJ, Williams AE, Mercer PF, Sulikowski MG, Brown JS, Chambers RC (Jun 2015). "Regulation of neutrophilic inflammation by proteinase-activated receptor 1 during bacterial pulmonary infection". Journal of Immunology 194 (12): 6024–34. doi:10.4049/jimmunol.1500124. PMID 25948816.

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.
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.
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.
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.
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.

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

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

Adhesion	ADGRG (1 2 3 4 5 6 7)

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 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60)

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

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Coagulation factor II receptor

Ligands

See also

References

Further reading