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Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 337 | Xq21.1 | CYSLTR1 | cysteinyl leukotriene receptor 1 | 42,78 |
| Mouse | 7 | 352 | X D | Cysltr1 | cysteinyl leukotriene receptor 1 | |
| Rat | 7 | 339 | Xq22 | Cysltr1 | cysteinyl leukotriene receptor 1 | |
| Previous and Unofficial Names |
| HG55 | LTD4 | CYSLT1R | leukotriene D4 receptor |
| Database Links |
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| Specialist databases | |
| GPCRdb | cltr1_human (Hs), cltr1_mouse (Mm), cltr1_rat (Rn) |
| Other databases | |
| Alphafold | Q9Y271 (Hs), Q99JA4 (Mm), Q924T8 (Rn) |
| ChEMBL Target | CHEMBL1798 (Hs), CHEMBL3808269 (Mm), CHEMBL1075218 (Rn) |
| DrugBank Target | Q9Y271 (Hs) |
| Ensembl Gene | ENSG00000173198 (Hs), ENSMUSG00000052821 (Mm), ENSRNOG00000037845 (Rn) |
| Entrez Gene | 10800 (Hs), 58861 (Mm), 114099 (Rn) |
| Human Protein Atlas | ENSG00000173198 (Hs) |
| KEGG Gene | hsa:10800 (Hs), mmu:58861 (Mm), rno:114099 (Rn) |
| OMIM | 300201 (Hs) |
| Pharos | Q9Y271 (Hs) |
| RefSeq Nucleotide | NM_006639 (Hs), NM_021476 (Mm), NM_053641 (Rn) |
| RefSeq Protein | NP_006630 (Hs), NP_067451 (Mm), NP_446093 (Rn) |
| UniProtKB | Q9Y271 (Hs), Q99JA4 (Mm), Q924T8 (Rn) |
| Wikipedia | CYSLTR1 (Hs) |
| Selected 3D Structures |
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| Natural/Endogenous Ligands |
| LTC4 |
| LTD4 |
| LTE4 |
| Comments: LTD4 is the most potent endogenous agonist |
| Potency order of endogenous ligands |
| LTD4 > LTC4 > LTE4 [42,78] |
Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immunopharmacology Comments |
| CysLT1 is a receptor for cysteinyl-leukotrienes. Both CysLT1 and CysLT2 mediate cysteinyl-leukotriene-induced modulation of smooth muscle cell contraction, regulation of vascular permeability, and leukocyte activation. Selective inhibition of CysLT1 receptor blocks the pro-inflammatory responses associated with allergic disorders that are mediated by this receptor. This pharmacological approach has been used for treating asthma and associated diseases for a considerable period of time, with several CysLT1-selective antagonists in clinical use. |
| Immuno Process Associations | ||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gq/G11 family | Phospholipase C stimulation |
| Comments: PI turnover and Ca2+ mobilisation. A number of different groups have reported a Gq/G11-dependent Ca2+ mobilization in monocytic leukemia U937 [10,68,92] or THP-1 cells [16,33], mast cells [54] or monocyte-derived macrophages [43] | |
| References: 42,78 | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
| Gi/Go family | Phospholipase C stimulation |
| Comments: Other different cellular responses have been reported to be Gi/G0 coupled [2,4,14,21,33,38,63,65,74,76,79,82,93]. | |
| References: 10,68,81 | |
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| Physiological Functions
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| Physiological Functions Comments | ||||||||
| Some physiological functions in cells expressing both CysLT1 and CysLT2 (e.g. eosinophils chemotaxis and adhesion) have been attributed to CysLT1 on the base of antagonist effect [55-56,77,88] However, most leukotriene receptor antagonist, but montelukast and MK-571, are also active at the CysLT2 and, thus, preclude unambiguous identification. | ||||||||
| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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| General Comments |
| LTE4 may be the only selective agonist as LTC4 and LTD4 also activate CysLT2 receptors. However, when Ca2+ mobilisation is studied in transfected cells, LTE4 is much less potent than LTD4. |
1. Adelroth E, Morris MM, Hargreave FE, O'Byrne PM. (1986) Airway responsiveness to leukotrienes C4 and D4 and to methacholine in patients with asthma and normal controls. N Engl J Med, 315 (8): 480-4. [PMID:3526153]
2. Bandeira-Melo C, Hall JC, Penrose JF, Weller PF. (2002) Cysteinyl leukotrienes induce IL-4 release from cord blood-derived human eosinophils. J Allergy Clin Immunol, 109 (6): 975-9. [PMID:12063527]
3. Barnes NC, Piper PJ, Costello JF. (1984) Comparative effects of inhaled leukotriene C4, leukotriene D4, and histamine in normal human subjects. Thorax, 39 (7): 500-4. [PMID:6463929]
4. Bautz F, Denzlinger C, Kanz L, Möhle R. (2001) Chemotaxis and transendothelial migration of CD34(+) hematopoietic progenitor cells induced by the inflammatory mediator leukotriene D4 are mediated by the 7-transmembrane receptor CysLT1. Blood, 97 (11): 3433-40. [PMID:11369634]
5. Beller TC, Friend DS, Maekawa A, Lam BK, Austen KF, Kanaoka Y. (2004) Cysteinyl leukotriene 1 receptor controls the severity of chronic pulmonary inflammation and fibrosis. Proc Natl Acad Sci USA, 101 (9): 3047-52. [PMID:14970333]
6. Bengtsson AM, Massoumi R, Sjölander A. (2008) Leukotriene D(4) induces AP-1 but not NFkappaB signaling in intestinal epithelial cells. Prostaglandins Other Lipid Mediat, 85 (3-4): 100-6. [PMID:18083053]
7. Boehmler AM, Drost A, Jaggy L, Seitz G, Wiesner T, Denzlinger C, Kanz L, Möhle R. (2009) The CysLT1 ligand leukotriene D4 supports alpha4beta1- and alpha5beta1-mediated adhesion and proliferation of CD34+ hematopoietic progenitor cells. J Immunol, 182 (11): 6789-98. [PMID:19454674]
8. Bossé Y, Thompson C, McMahon S, Dubois CM, Stankova J, Rola-Pleszczynski M. (2008) Leukotriene D4-induced, epithelial cell-derived transforming growth factor beta1 in human bronchial smooth muscle cell proliferation. Clin Exp Allergy, 38 (1): 113-21. [PMID:18028462]
9. Braccioni F, Dorman SC, O'byrne PM, Inman MD, Denburg JA, Parameswaran K, Baatjes AJ, Foley R, Gauvreau GM. (2002) The effect of cysteinyl leukotrienes on growth of eosinophil progenitors from peripheral blood and bone marrow of atopic subjects. J Allergy Clin Immunol, 110 (1): 96-101. [PMID:12110827]
10. Capra V, Accomazzo MR, Ravasi S, Parenti M, Macchia M, Nicosia S, Rovati GE. (2003) Involvement of prenylated proteins in calcium signaling induced by LTD4 in differentiated U937 cells. Prostaglandins Other Lipid Mediat, 71 (3-4): 235-51. [PMID:14518564]
11. Capra V, Bolla M, Belloni PA, Mezzetti M, Folco GC, Nicosia S, Rovati GE. (1998) Pharmacological characterization of the cysteinyl-leukotriene antagonists CGP 45715A (iralukast) and CGP 57698 in human airways in vitro. Br J Pharmacol, 123 (3): 590-8. [PMID:9504401]
12. Capra V, Nicosia S, Ragnini D, Mezzetti M, Keppler D, Rovati GE. (1998) Identification and characterization of two cysteinyl-leukotriene high affinity binding sites with receptor characteristics in human lung parenchyma. Mol Pharmacol, 53 (4): 750-8. [PMID:9547367]
13. Capra V, Ravasi S, Accomazzo MR, Citro S, Grimoldi M, Abbracchio MP, Rovati GE. (2005) CysLT1 receptor is a target for extracellular nucleotide-induced heterologous desensitization: a possible feedback mechanism in inflammation. J Cell Sci, 118 (Pt 23): 5625-36. [PMID:16306225]
14. Capra V, Ravasi S, Accomazzo MR, Parenti M, Rovati GE. (2004) CysLT1 signal transduction in differentiated U937 cells involves the activation of the small GTP-binding protein Ras. Biochem Pharmacol, 67 (8): 1569-77. [PMID:15041474]
15. Carnini C, Accomazzo MR, Borroni E, Vitellaro-Zuccarello L, Durand T, Folco G, Rovati GE, Capra V, Sala A. (2011) Synthesis of cysteinyl leukotrienes in human endothelial cells: subcellular localization and autocrine signaling through the CysLT2 receptor. FASEB J, 25 (10): 3519-28. [PMID:21753081]
16. Chan CC, Ecclestone P, Nicholson DW, Metters KM, Pon DJ, Rodger IW. (1994) Leukotriene D4-induced increases in cytosolic calcium in THP-1 cells: dependence on extracellular calcium and inhibition with selective leukotriene D4 receptor antagonists. J Pharmacol Exp Ther, 269 (3): 891-6. [PMID:8014876]
17. Chao SS, Graham SM, Brown CL, Kline JN, Hussain I. (2006) Cysteinyl leukotriene 1 receptor expression in nasal polyps. Ann Otol Rhinol Laryngol, 115 (5): 394-7. [PMID:16739673]
18. Ciccarelli R, D'Alimonte I, Santavenere C, D'Auro M, Ballerini P, Nargi E, Buccella S, Nicosia S, Folco G, Caciagli F et al.. (2004) Cysteinyl-leukotrienes are released from astrocytes and increase astrocyte proliferation and glial fibrillary acidic protein via cys-LT1 receptors and mitogen-activated protein kinase pathway. Eur J Neurosci, 20 (6): 1514-24. [PMID:15355318]
19. Davidson AB, Lee TH, Scanlon PD, Solway J, McFadden Jr ER, Ingram Jr RH, Corey EJ, Austen KF, Drazen JM. (1987) Bronchoconstrictor effects of leukotriene E4 in normal and asthmatic subjects. Am Rev Respir Dis, 135 (2): 333-7. [PMID:3028218]
20. Drazen JM, Austen KF, Lewis RA, Clark DA, Goto G, Marfat A, Corey EJ. (1980) Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro. Proc Natl Acad Sci USA, 77 (7): 4354-8. [PMID:6933488]
21. Drost AC, Seitz G, Boehmler A, Funk M, Norz KP, Zipfel A, Xue X, Kanz L, Möhle R. (2012) The G protein-coupled receptor CysLT1 mediates chemokine-like effects and prolongs survival in chronic lymphocytic leukemia. Leuk Lymphoma, 53 (4): 665-73. [PMID:21936770]
22. Eap R, Jacques E, Semlali A, Plante S, Chakir J. (2012) Cysteinyl leukotrienes regulate TGF-β(1) and collagen production by bronchial fibroblasts obtained from asthmatic subjects. Prostaglandins Leukot Essent Fatty Acids, 86 (3): 127-33. [PMID:22316690]
23. Eaton A, Nagy E, Pacault M, Fauconnier J, Bäck M. (2012) Cysteinyl leukotriene signaling through perinuclear CysLT(1) receptors on vascular smooth muscle cells transduces nuclear calcium signaling and alterations of gene expression. J Mol Med, 90 (10): 1223-31. [PMID:22527886]
24. Espinosa K, Bossé Y, Stankova J, Rola-Pleszczynski M. (2003) CysLT1 receptor upregulation by TGF-beta and IL-13 is associated with bronchial smooth muscle cell proliferation in response to LTD4. J Allergy Clin Immunol, 111 (5): 1032-40. [PMID:12743568]
25. Figueroa DJ, Breyer RM, Defoe SK, Kargman S, Daugherty BL, Waldburger K, Liu Q, Clements M, Zeng Z, O'Neill GP et al.. (2001) Expression of the cysteinyl leukotriene 1 receptor in normal human lung and peripheral blood leukocytes. Am J Respir Crit Care Med, 163 (1): 226-33. [PMID:11208650]
26. Fregonese L, Silvestri M, Sabatini F, Rossi GA. (2002) Cysteinyl leukotrienes induce human eosinophil locomotion and adhesion molecule expression via a CysLT1 receptor-mediated mechanism. Clin Exp Allergy, 32 (5): 745-50. [PMID:11994100]
27. Frieri M, Therattil J, Wang SF, Huang CY, Wang YC. (2003) Montelukast inhibits interleukin-5 mRNA expression and cysteinyl leukotriene production in ragweed and mite-stimulated peripheral blood mononuclear cells from patients with asthma. Allergy Asthma Proc, 24 (5): 359-66. [PMID:14619337]
28. Galemmo RA Jr, Johnson WH Jr, Learn KS, Lee TD, Huang FC, Campbell HF, Youssefyeh R, O'Rourke SV, Schuessler G, Sweeney DM et al.. (1990) The development of a novel series of (quinolin-2-ylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 3. Structural variation of the acidic side chain to give antagonists of enhanced potency. J Med Chem, 33 (10): 2828-41. [PMID:2170649]
29. Griffin M, Weiss JW, Leitch AG, McFadden Jr ER, Corey EJ, Austen KF, Drazen JM. (1983) Effects of leukotriene D on the airways in asthma. N Engl J Med, 308 (8): 436-9. [PMID:6823253]
30. Gusach A, Luginina A, Marin E, Brouillette RL, Besserer-Offroy É, Longpré JM, Ishchenko A, Popov P, Patel N, Fujimoto T et al.. (2019) Structural basis of ligand selectivity and disease mutations in cysteinyl leukotriene receptors. Nat Commun, 10 (1): 5573. DOI: 10.1038/s41467-019-13348-2 [PMID:31811124]
31. Hasegawa S, Ichiyama T, Hashimoto K, Suzuki Y, Hirano R, Fukano R, Furukawa S. (2010) Functional expression of cysteinyl leukotriene receptors on human platelets. Platelets, 21 (4): 253-9. [PMID:20433311]
32. Hashimoto K, Ichiyama T, Hasegawa M, Hasegawa S, Matsubara T, Furukawa S. (2009) Cysteinyl leukotrienes induce monocyte chemoattractant protein-1 in human monocyte/macrophages via mitogen-activated protein kinase and nuclear factor-kappaB pathways. Int Arch Allergy Immunol, 149 (3): 275-82. [PMID:19218821]
33. Hoshino M, Izumi T, Shimizu T. (1998) Leukotriene D4 activates mitogen-activated protein kinase through a protein kinase Calpha-Raf-1-dependent pathway in human monocytic leukemia THP-1 cells. J Biol Chem, 273 (9): 4878-82. [PMID:9478929]
34. Huang XJ, Zhang WP, Li CT, Shi WZ, Fang SH, Lu YB, Chen Z, Wei EQ. (2008) Activation of CysLT receptors induces astrocyte proliferation and death after oxygen-glucose deprivation. Glia, 56 (1): 27-37. [PMID:17910051]
35. Ichiyama T, Hasegawa M, Hashimoto K, Matsushige T, Hirano R, Furukawa S. (2009) Cysteinyl leukotrienes induce macrophage inflammatory protein-1 in human monocytes/macrophages. Int Arch Allergy Immunol, 148 (2): 147-53. [PMID:18802359]
36. Ichiyama T, Hasegawa M, Ueno Y, Makata H, Matsubara T, Furukawa S. (2005) Cysteinyl leukotrienes induce monocyte chemoattractant protein 1 in human monocytes/macrophages. Clin Exp Allergy, 35 (9): 1214-9. [PMID:16164450]
37. Ichiyama T, Kajimoto M, Hasegawa M, Hashimoto K, Matsubara T, Furukawa S. (2007) Cysteinyl leukotrienes enhance tumour necrosis factor-alpha-induced matrix metalloproteinase-9 in human monocytes/macrophages. Clin Exp Allergy, 37 (4): 608-14. [PMID:17430359]
38. Jiang Y, Kanaoka Y, Feng C, Nocka K, Rao S, Boyce JA. (2006) Cutting edge: Interleukin 4-dependent mast cell proliferation requires autocrine/intracrine cysteinyl leukotriene-induced signaling. J Immunol, 177 (5): 2755-9. [PMID:16920908]
39. Jones TR, Zamboni R, Belley M, Champion E, Charette L, Ford-Hutchinson AW, Gauthier JY, Leger S, Lord A, Masson P et al.. (1991) Pharmacology of the leukotriene antagonist verlukast: the (R)-enantiomer of MK-571. Can J Physiol Pharmacol, 69 (12): 1847-54. [PMID:1666333]
40. Kern R, Smith LJ, Patterson R, Krell RD, Bernstein PR. (1986) Characterization of the airway response to inhaled leukotriene D4 in normal subjects. Am Rev Respir Dis, 133 (6): 1127-32. [PMID:3521417]
41. Kushiya M, Saito K, Kikuchi I, Kobayashi T, Hagiwara K, Kanazawa M, Nagata M. (2006) Differential effects of salbutamol and montelukast on eosinophil adhesion and superoxide anion generation. Int Arch Allergy Immunol, 140 Suppl 1: 17-22. [PMID:16772722]
42. Lynch KR, O'Neill GP, Liu Q, Im DS, Sawyer N, Metters KM, Coulombe N, Abramovitz M, Figueroa DJ, Zeng Z et al.. (1999) Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature, 399 (6738): 789-93. [PMID:10391245]
43. Lötzer K, Spanbroek R, Hildner M, Urbach A, Heller R, Bretschneider E, Galczenski H, Evans JF, Habenicht AJ. (2003) Differential leukotriene receptor expression and calcium responses in endothelial cells and macrophages indicate 5-lipoxygenase-dependent circuits of inflammation and atherogenesis. Arterioscler Thromb Vasc Biol, 23 (8): e32-6. [PMID:12816882]
44. Maekawa A, Austen KF, Kanaoka Y. (2002) Targeted gene disruption reveals the role of cysteinyl leukotriene 1 receptor in the enhanced vascular permeability of mice undergoing acute inflammatory responses. J Biol Chem, 277 (23): 20820-4. [PMID:11932261]
45. Massoumi R, Larsson C, Sjölander A. (2002) Leukotriene D(4) induces stress-fibre formation in intestinal epithelial cells via activation of RhoA and PKCdelta. J Cell Sci, 115 (Pt 17): 3509-15. [PMID:12154081]
46. Massoumi R, Nielsen CK, Azemovic D, Sjölander A. (2003) Leukotriene D4-induced adhesion of Caco-2 cells is mediated by prostaglandin E2 and upregulation of alpha2beta1-integrin. Exp Cell Res, 289 (2): 342-51. [PMID:14499635]
47. Massoumi R, Sjölander A. (1998) The inflammatory mediator leukotriene D4 triggers a rapid reorganisation of the actin cytoskeleton in human intestinal epithelial cells. Eur J Cell Biol, 76 (3): 185-91. [PMID:9716265]
48. Massoumi R, Sjölander A. (2001) Leukotriene D(4) affects localisation of vinculin in intestinal epithelial cells via distinct tyrosine kinase and protein kinase C controlled events. J Cell Sci, 114 (Pt 10): 1925-34. [PMID:11329379]
49. Matsuyama M, Hayama T, Funao K, Kawahito Y, Sano H, Takemoto Y, Nakatani T, Yoshimura R. (2007) Overexpression of cysteinyl LT1 receptor in prostate cancer and CysLT1R antagonist inhibits prostate cancer cell growth through apoptosis. Oncol Rep, 18 (1): 99-104. [PMID:17549353]
50. Mattern MR, Mong S, Mong SM, Bartus JO, Sarau HM, Clark MA, Foley JJ, Crooke ST. (1990) Transient activation of topoisomerase I in leukotriene D4 signal transduction in human cells. Biochem J, 265 (1): 101-7. [PMID:2154178]
51. Mechiche H, Candenas L, Pinto FM, Nazeyrollas P, Clément C, Devillier P. (2004) Characterization of cysteinyl leukotriene receptors on human saphenous veins: antagonist activity of montelukast and its metabolites. J Cardiovasc Pharmacol, 43 (1): 113-20. [PMID:14668576]
52. Meliton AY, Munoz NM, Leff AR. (2007) Blockade of avidity and focal clustering of beta 2-integrin by cysteinyl leukotriene antagonism attenuates eosinophil adhesion. J Allergy Clin Immunol, 120 (6): 1316-23. [PMID:17904626]
53. Meliton AY, Muñoz NM, Osan CM, Meliton LN, Leff AR. (2010) Leukotriene D4 activates {beta}2-integrin adhesion in human polymorphonuclear leukocytes. Eur Respir J, 35 (2): 402-9. [PMID:19679609]
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target has curated data in GtoImmuPdb
