protease-activated receptor 1

• プロテアーゼ活性化受容体1

関

PAR-1、PAR-1 receptor、proteinase-activated receptor 1

WordNet

1. aerate (sewage) so as to favor the growth of organisms that decompose organic matter (同)aerate
2. make (substances) radioactive
3. make active or more active; "activate an old file"
4. make more adsorptive; "activate a metal"
5. rendered active; e.g. rendered radioactive or luminescent or photosensitive or conductive
6. (of e.g. a molecule) made reactive or more reactive (同)excited
7. (military) set up and placed on active assignment; "a newly activated unit"
8. (of sewage) treated with aeration and bacteria to aid decomposition
9. a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
10. any enzyme that catalyzes the splitting of proteins into smaller peptide fractions and amino acids by a process known as proteolysis (同)peptidase, proteinase, proteolytic_enzyme
11. any tropical African shrub of the genus Protea having alternate rigid leaves and dense colorful flower heads resembling cones

PrepTutorEJDIC

1. …'を'活動的にする / …‘に'放射能を与える / 〈物質〉'を'活性化する
2. =sense organ / 受信装置

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/04/02 10:09:01」(JST)

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[Wiki en表示]

"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 PDB 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
Entrez	2149	14062
Ensembl	ENSG00000181104	ENSMUSG00000048376
UniProt	P25116	P30558
RefSeq (mRNA)	NM_001311313	NM_010169
RefSeq (protein)	NP_001298242	NP_034299
Location (UCSC)	Chr 5: 76.72 – 76.74 Mb	Chr 13: 95.6 – 95.62 Mb
PubMed search	[1]	[2]

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. 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.

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

References

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. 
• 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.

UpToDate Contents

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English Journal

• Thrombin induces slug-mediated E-cadherin transcriptional repression and the parallel Up-regulation of N-cadherin by a transcription-independent mechanism in RPE cells.

• Palma-Nicolás JP, López-Colomé AM.SourceDivisión de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Mexico, D.F., Mexico.
• Journal of cellular physiology.J Cell Physiol.2013 Mar;228(3):581-9. doi: 10.1002/jcp.24165.
• The proliferation, directional migration to the vitreous and epithelial-mesenchymal transition (EMT) of quiescent, differentiated retinal pigment epithelium (RPE) cells is a major feature in the development of proliferative vitreoretinopathy (PVR) following exposure of the immuno-privileged eye nich
• PMID 22833386

• Inhibition of Protease-activated Receptor 1 Ameliorates Intestinal Radiation Mucositis in a Preclinical Rat Model.

• Wang J, Kulkarni A, Chintala M, Fink LM, Hauer-Jensen M.SourceDivision of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
• International journal of radiation oncology, biology, physics.Int J Radiat Oncol Biol Phys.2013 Jan 1;85(1):208-14. doi: 10.1016/j.ijrobp.2012.02.007. Epub 2012 May 12.
• PURPOSE: To determine, using a specific small-molecule inhibitor of protease-activated receptor 1 (PAR1) signaling, whether the beneficial effect of thrombin inhibition on radiation enteropathy development is due to inhibition of blood clotting or to cellular (PAR1-mediated) thrombin effects.METHODS
• PMID 22580123

Japanese Journal

• トロンビン受容体PAR1の立体構造

• 千々岩 崇仁,武谷 浩之
• 日本血栓止血学会誌 24(4), 454-459, 2013
• … ❖Points❖①PAR1（protease activated receptor 1）とそのアンタゴニストであるボラパクサール（vorapaxar）の複合体の結晶構造が決定された．②PAR1のリガンド結合ポケットは，他のG蛋白共役型受容体とは異なり，閉じている．③ボラパクサールはPAR1分子の表面近傍において，洞窟の中にはまり込むようにして結合しており，ほとんど溶媒に曝されていない．④この特徴的な結合様式は，ボ …
• NAID 130003367371

• Protease-Activated Receptor-Stimulated Interleukin-6 Expression in Endometriosis-Like Lesions in an Experimental Mouse Model of Endometriosis

• Shinohara Akihiro,Kutsukake Masahiko,Takahashi Mirai [他],KYO Satoru,TACHIKAWA Eiichi,TAMURA Kazuhiro
• Journal of pharmacological sciences 119(1), 40-51, 2012-05-20
• … The present study was undertaken to investigate the function of protease-activated receptor (PAR) in endometriotic lesions using a mouse model of endometriosis. … IL-6 expression induced by PAR activation was blocked by the treatment of cells with serine protease inhibitors. …
• NAID 10030760253

• 慢性腎臓病（CKD）における凝固系と凝固第Xa因子の役割

• 小野 孝彦
• YAKUGAKU ZASSHI 132(4), 449-453, 2012
• … Factor Xa activates various cell types through protease-activated receptor 2 (PAR2). …
• NAID 130001872047

Related Links

• 研究1

Protease activated receptor (PAR) の活性化機構： PARは、蛋白質分解酵素により、その細胞外領域の特定の部位が切断されると。新たに生じたN末端領域が受容体に作用し、活性化される。

• Protease activated receptor 2とは - goo Wikipedia (ウィキペディア)

Protease activated receptor 2 (PAR2) also known as coagulation factor II (thrombin) receptor-like 1 (F2RL1) or G-protein coupled receptor 11 (GPR11) is a protein that in humans is encoded by the F2RL1 gene. PAR2 modulates ...

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★リンクテーブル★

リンク元	「PAR-1 receptor」「プロテアーゼ活性化受容体1」「PAR-1」「proteinase-activated receptor 1」
関連記事	「activated」「activate」

「PAR-1 receptor」

　　[★]

• プロテアーゼ活性化受容体1、プロテアーゼ活性化レセプター1、PAR-1受容体、PAR-1レセプター

関

PAR-1、protease-activated receptor 1、proteinase-activated receptor 1

「プロテアーゼ活性化受容体1」

　　[★]

英

protease-activated receptor 1、proteinase-activated receptor 1、PAR-1 receptor、PAR-1

関

PAR-1受容体、プロテアーゼ活性化レセプター1、PAR-1レセプター

「PAR-1」

　　[★]

• プロテアーゼ活性化受容体1

関

PAR-1 receptor、protease-activated receptor 1、proteinase-activated receptor 1

「proteinase-activated receptor 1」

　　[★]

• プロテアーゼ活性化受容体1

関

PAR-1、PAR-1 receptor、protease-activated receptor 1

「activated」

　　[★]

• adj.

• 活性化の、活性化型の、賦活化の

関

activate、activated form、activation、turn on

　 　 　 　

「activate」

　　[★]

• v.

• 活性化する、賦活化する、賦活する

関

activated、activation、turn on