Coagulation factor II receptor

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

F2R

Available structures

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

MGI: 101802 HomoloGene: 1510 GeneCards: F2R

Targeted by Drug

vorapaxar^[1]

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 • 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	• positive regulation of Rho protein signal transduction • negative regulation of neuron apoptotic process • positive regulation of collagen biosynthetic process • hemostasis • G-protein coupled receptor signaling pathway • establishment of synaptic specificity at neuromuscular junction • release of sequestered calcium ion into cytosol • positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway • platelet dense granule organization • positive regulation of interleukin-6 secretion • regulation of sensory perception of pain • thrombin-activated receptor signaling pathway • activation of MAPKK activity • 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 • STAT protein import into nucleus • tyrosine phosphorylation of STAT protein • 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 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 • positive regulation of interleukin-8 secretion • 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 JAK-STAT cascade • positive regulation of MAPK cascade • negative regulation of cell proliferation • negative regulation of renin secretion into blood stream • signal transduction • positive regulation of calcium ion transport
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


2149


14062

Ensembl


ENSG00000181104


ENSMUSG00000048376

UniProt


P25116


P30558

RefSeq (mRNA)


NM_001992 NM_001311313


NM_010169

RefSeq (protein)


NP_001298242.1 NP_001983.2


NP_034299.2

Location (UCSC)

Chr 5: 76.72 – 76.74 Mb

Chr 13: 95.6 – 95.62 Mb

PubMed search

^[2]

^[3]

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.^[4] PAR1 is a G protein-coupled receptor involved in the regulation of thrombotic response. Proteolytic cleavage leads to the activation of the receptor.^[5]

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.^[6] It is involved both in disruption and maintaining of endothelial barrier integrity, through interaction with either thrombin or activated protein C, respectively.^[7]

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.^[8]

References

↑ "Drugs that physically interact with Proteinase-activated receptor 1 view/edit references on wikidata".
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ 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.
↑ Feistritzer C, Riewald M (Apr 2005). "Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1–phosphate receptor-1 crossactivation". blood. 105 (8): 3178–84. doi:10.1182/blood-2004-10-3985. PMID 15626732.
↑ 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 Vomeronasal receptor)

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