Target has curated data in GtoImmuPdb
Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Natural/Endogenous Ligands
- Rank order lists
- Agonists
- Antagonists
- Immunopharmacology Comments
- Immuno Process Associations
- Immuno Disease Associations
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Biologically Significant Variants
- General Comments
- References
- Contributors
- How to cite this page
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 | 352 | 14q12 | LTB4R | leukotriene B4 receptor | 3,69 |
| Mouse | 7 | 351 | 14 28.19 cM | Ltb4r1 | leukotriene B4 receptor 1 | 27 |
| Rat | 7 | 351 | 15p13 | Ltb4r | leukotriene B4 receptor | 65 |
| Previous and Unofficial Names |
| BLTR | GPR16 |
| Database Links |
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| Specialist databases | |
| GPCRdb | lt4r1_human (Hs), lt4r1_mouse (Mm), lt4r1_rat (Rn) |
| Other databases | |
| Alphafold | Q15722 (Hs), O88855 (Mm), Q9R0Q2 (Rn) |
| ChEMBL Target | CHEMBL3911 (Hs), CHEMBL2657 (Mm), CHEMBL2126 (Rn) |
| Ensembl Gene | ENSG00000213903 (Hs), ENSMUSG00000046908 (Mm), ENSRNOG00000020399 (Rn) |
| Entrez Gene | 1241 (Hs), 16995 (Mm), 59264 (Rn) |
| Human Protein Atlas | ENSG00000213903 (Hs) |
| KEGG Gene | hsa:1241 (Hs), mmu:16995 (Mm), rno:59264 (Rn) |
| OMIM | 601531 (Hs) |
| Pharos | Q15722 (Hs) |
| RefSeq Nucleotide | NM_181657 (Hs), NM_008519 (Mm), NM_021656 (Rn) |
| RefSeq Protein | NP_858043 (Hs), NP_032545 (Mm), NP_067688 (Rn) |
| UniProtKB | Q15722 (Hs), O88855 (Mm), Q9R0Q2 (Rn) |
| Wikipedia | LTB4R (Hs) |
| Natural/Endogenous Ligands |
| 20-hydroxy-LTB4 |
| LTB4 |
| 12R-HETE |
| Comments: LTB4 is the most potent endogenous agonist |
| Potency order of endogenous ligands |
| LTB4 >20-hydroxy-LTB4 >>12R-HETE [71] |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immunopharmacology Comments |
| The human BLT1 receptor is the high affinity leukotriene B4 receptor, involved in mediating chemotaxis and activation of several leukocyte populations, including granulocytes, monocytes/macrophages, and lymphocytes [52]. |
| Immuno Process Associations | ||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
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Gi/Go family Gq/G11 family |
Adenylyl cyclase inhibition Phospholipase C stimulation Other - See Comments |
| Comments: Mitogen-activated protein kinase activation. In CHO cells, LTB4-elicited activation of phospholipase C is mediated via BLT1/Gα16 pathway. | |
| References: 8,11,16,20,50,69 | |
| Tissue Distribution
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| Expression Datasets |
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| Physiological Functions Comments | ||||||||
| Implicated in chemotaxis and leukocyte activation. Real-time imaging of BLT1/β-arrestin interaction and LTB4-induced cell migration is described by [33]. | ||||||||
| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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| Biologically Significant Variants
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| General Comments |
| Helix 8 of C-terminal tail is important for the inactivation of BLT1 [46] and inhibits ligand-induced receptor internalization [4]. |
References
1. Ahluwalia N, Lin AY, Tager AM, Pruitt IE, Anderson TJ, Kristo F, Shen D, Cruz AR, Aikawa M, Luster AD et al.. (2007) Inhibited aortic aneurysm formation in BLT1-deficient mice. J Immunol, 179 (1): 691-7. [PMID:17579092]
2. Aiello RJ, Bourassa PA, Lindsey S, Weng W, Freeman A, Showell HJ. (2002) Leukotriene B4 receptor antagonism reduces monocytic foam cells in mice. Arterioscler Thromb Vasc Biol, 22 (3): 443-9. [PMID:11884288]
3. Akbar GK, Dasari VR, Webb TE, Ayyanathan K, Pillarisetti K, Sandhu AK, Athwal RS, Daniel JL, Ashby B, Barnard EA et al.. (1996) Molecular cloning of a novel P2 purinoceptor from human erythroleukemia cells. J Biol Chem, 271 (31): 18363-7. [PMID:8702478]
4. Aratake Y, Okuno T, Matsunobu T, Saeki K, Takayanagi R, Furuya S, Yokomizo T. (2012) Helix 8 of leukotriene B4 receptor 1 inhibits ligand-induced internalization. FASEB J, 26 (10): 4068-78. [PMID:22707565]
5. Bevan S, Dichgans M, Wiechmann HE, Gschwendtner A, Meitinger T, Markus HS. (2008) Genetic variation in members of the leukotriene biosynthesis pathway confer an increased risk of ischemic stroke: a replication study in two independent populations. Stroke, 39 (4): 1109-14. [PMID:18323512]
6. Birke FW, Meade CJ, Anderskewitz R, Speck GA, Jennewein HM. (2001) In vitro and in vivo pharmacological characterization of BIIL 284, a novel and potent leukotriene B(4) receptor antagonist. J Pharmacol Exp Ther, 297 (1): 458-66. [PMID:11259574]
7. Boie Y, Stocco R, Sawyer N, Greig GM, Kargman S, Slipetz DM, O'Neill GP, Shimizu T, Yokomizo T, Metters KM et al.. (1999) Characterization of the cloned guinea pig leukotriene B4 receptor: comparison to its human orthologue. Eur J Pharmacol, 380 (2-3): 203-13. [PMID:10513580]
8. Brink C, Dahlén SE, Drazen J, Evans JF, Hay DW, Nicosia S, Serhan CN, Shimizu T, Yokomizo T. (2003) International Union of Pharmacology XXXVII. Nomenclature for leukotriene and lipoxin receptors. Pharmacol Rev, 55 (1): 195-227. [PMID:12615958]
9. Bäck M, Bu DX, Bränström R, Sheikine Y, Yan ZQ, Hansson GK. (2005) Leukotriene B4 signaling through NF-kappaB-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia. Proc Natl Acad Sci USA, 102 (48): 17501-6. [PMID:16293697]
10. Bäck M, Hansson GK. (2006) Leukotriene receptors in atherosclerosis. Ann Med, 38 (7): 493-502. [PMID:17101540]
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. Chiang N, Gronert K, Clish CB, O'Brien JA, Freeman MW, Serhan CN. (1999) Leukotriene B4 receptor transgenic mice reveal novel protective roles for lipoxins and aspirin-triggered lipoxins in reperfusion. J Clin Invest, 104 (3): 309-16. [PMID:10430612]
13. Chou RC, Kim ND, Sadik CD, Seung E, Lan Y, Byrne MH, Haribabu B, Iwakura Y, Luster AD. (2010) Lipid-cytokine-chemokine cascade drives neutrophil recruitment in a murine model of inflammatory arthritis. Immunity, 33 (2): 266-78. [PMID:20727790]
14. Díaz-González F, Alten RH, Bensen WG, Brown JP, Sibley JT, Dougados M, Bombardieri S, Durez P, Ortiz P, de-Miquel G et al.. (2007) Clinical trial of a leucotriene B4 receptor antagonist, BIIL 284, in patients with rheumatoid arthritis. Ann Rheum Dis, 66 (5): 628-32. [PMID:17170051]
15. Friedrich EB, Tager AM, Liu E, Pettersson A, Owman C, Munn L, Luster AD, Gerszten RE. (2003) Mechanisms of leukotriene B4--triggered monocyte adhesion. Arterioscler Thromb Vasc Biol, 23 (10): 1761-7. [PMID:12947016]
16. Gaudreau R, Le Gouill C, Métaoui S, Lemire S, Stankovà J, Rola-Pleszczynski M. (1998) Signalling through the leukotriene B4 receptor involves both alphai and alpha16, but not alphaq or alpha11 G-protein subunits. Biochem J, 335 ( Pt 1): 15-8. [PMID:9742207]
17. Goodarzi K, Goodarzi M, Tager AM, Luster AD, von Andrian UH. (2003) Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues. Nat Immunol, 4 (10): 965-73. [PMID:12949533]
18. Griffiths RJ, Pettipher ER, Koch K, Farrell CA, Breslow R, Conklyn MJ, Smith MA, Hackman BC, Wimberly DJ, Milici AJ et al.. (1995) Leukotriene B4 plays a critical role in the progression of collagen-induced arthritis. Proc Natl Acad Sci USA, 92 (2): 517-21. [PMID:7831322]
19. Haribabu B, Verghese MW, Steeber DA, Sellars DD, Bock CB, Snyderman R. (2000) Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis. J Exp Med, 192 (3): 433-8. [PMID:10934231]
20. Haribabu B, Zhelev DV, Pridgen BC, Richardson RM, Ali H, Snyderman R. (1999) Chemoattractant receptors activate distinct pathways for chemotaxis and secretion. Role of G-protein usage. J Biol Chem, 274 (52): 37087-92. [PMID:10601267]
21. Hashimoto A, Endo H, Hayashi I, Murakami Y, Kitasato H, Kono S, Matsui T, Tanaka S, Nishimura A, Urabe K et al.. (2003) Differential expression of leukotriene B4 receptor subtypes (BLT1 and BLT2) in human synovial tissues and synovial fluid leukocytes of patients with rheumatoid arthritis. J Rheumatol, 30 (8): 1712-8. [PMID:12913925]
22. Heller EA, Liu E, Tager AM, Sinha S, Roberts JD, Koehn SL, Libby P, Aikawa ER, Chen JQ, Huang P et al.. (2005) Inhibition of atherogenesis in BLT1-deficient mice reveals a role for LTB4 and BLT1 in smooth muscle cell recruitment. Circulation, 112 (4): 578-86. [PMID:16043658]
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24. Hicks A, Goodnow Jr R, Cavallo G, Tannu SA, Ventre JD, Lavelle D, Lora JM, Satjawatcharaphong J, Brovarney M, Dabbagh K et al.. (2010) Effects of LTB4 receptor antagonism on pulmonary inflammation in rodents and non-human primates. Prostaglandins Other Lipid Mediat, 92 (1-4): 33-43. [PMID:20214997]
25. Hikiji H, Ishii S, Yokomizo T, Takato T, Shimizu T. (2009) A distinctive role of the leukotriene B4 receptor BLT1 in osteoclastic activity during bone loss. Proc Natl Acad Sci USA, 106 (50): 21294-9. [PMID:19965376]
26. Houard X, Ollivier V, Louedec L, Michel JB, Bäck M. (2009) Differential inflammatory activity across human abdominal aortic aneurysms reveals neutrophil-derived leukotriene B4 as a major chemotactic factor released from the intraluminal thrombus. FASEB J, 23 (5): 1376-83. [PMID:19136615]
27. Huang WW, Garcia-Zepeda EA, Sauty A, Oettgen HC, Rothenberg ME, Luster AD. (1998) Molecular and biological characterization of the murine leukotriene B4 receptor expressed on eosinophils. J Exp Med, 188 (6): 1063-74. [PMID:9743525]
28. Ihara A, Wada K, Yoneda M, Fujisawa N, Takahashi H, Nakajima A. (2007) Blockade of leukotriene B4 signaling pathway induces apoptosis and suppresses cell proliferation in colon cancer. J Pharmacol Sci, 103 (1): 24-32. [PMID:17220595]
29. Islam SA, Thomas SY, Hess C, Medoff BD, Means TK, Brander C, Lilly CM, Tager AM, Luster AD. (2006) The leukotriene B4 lipid chemoattractant receptor BLT1 defines antigen-primed T cells in humans. Blood, 107 (2): 444-53. [PMID:16179368]
30. Ito S, Ito Y, Katagiri H, Suzuki T, Hoka S, Yokomizo T, Shimizu T, Majima M. (2008) Leukotriene B4/leukotriene B4 receptor pathway is involved in hepatic microcirculatory dysfunction elicited by endotoxin. Shock, 30 (1): 87-91. [PMID:18004232]
31. Jackson RH, Morrissey MM, Sills MA, Jarvis MF. (1992) Comparison of antagonist and agonist binding to the leukotriene B4 receptor intact human polymorphonuclear neutrophils (PMN). J Pharmacol Exp Ther, 262 (1): 80-9. [PMID:1320692]
32. Jackson WT, Froelich LL, Boyd RJ, Schrementi JP, Saussy Jr DL, Schultz RM, Sawyer JS, Sofia MJ, Herron DK, Goodson Jr T et al.. (1999) Pharmacologic actions of the second-generation leukotriene B4 receptor antagonist LY293111: in vitro studies. J Pharmacol Exp Ther, 288 (1): 286-94. [PMID:9862783]
33. Jala VR, Haribabu B. (2010) Real-time imaging of leukotriene B₄ mediated cell migration and BLT1 interactions with β-arrestin. J Vis Exp, (46). [PMID:21206474]
34. Kihara Y, Yokomizo T, Kunita A, Morishita Y, Fukayama M, Ishii S, Shimizu T. (2010) The leukotriene B4 receptor, BLT1, is required for the induction of experimental autoimmune encephalomyelitis. Biochem Biophys Res Commun, 394 (3): 673-8. [PMID:20226760]
35. Kim ND, Chou RC, Seung E, Tager AM, Luster AD. (2006) A unique requirement for the leukotriene B4 receptor BLT1 for neutrophil recruitment in inflammatory arthritis. J Exp Med, 203 (4): 829-35. [PMID:16567386]
36. Kishikawa K, Tateishi N, Maruyama T, Seo R, Toda M, Miyamoto T. (1992) ONO-4057, a novel, orally active leukotriene B4 antagonist: effects on LTB4-induced neutrophil functions. Prostaglandins, 44 (4): 261-75. [PMID:1332129]
37. Li RC, Haribabu B, Mathis SP, Kim J, Gozal D. (2011) Leukotriene B4 receptor-1 mediates intermittent hypoxia-induced atherogenesis. Am J Respir Crit Care Med, 184 (1): 124-31. [PMID:21493735]
38. Marcinkiewicz J, Grabowska A, Bryniarski K, Chain BM. (1997) Enhancement of CD4+ T-cell-dependent interleukin-2 production in vitro by murine alveolar macrophages: the role of leukotriene B4. Immunology, 91 (3): 369-74. [PMID:9301525]
39. Marder P, Sawyer JS, Froelich LL, Mann LL, Spaethe SM. (1995) Blockade of human neutrophil activation by 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5- hydroxyphenoxy]propoxy]phenoxy]benzoic acid (LY293111), a novel leukotriene B4 receptor antagonist. Biochem Pharmacol, 49 (11): 1683-90. [PMID:7786309]
40. Mathis SP, Jala VR, Lee DM, Haribabu B. (2010) Nonredundant roles for leukotriene B4 receptors BLT1 and BLT2 in inflammatory arthritis. J Immunol, 185 (5): 3049-56. [PMID:20656922]
41. Miyahara N, Ohnishi H, Matsuda H, Miyahara S, Takeda K, Koya T, Matsubara S, Okamoto M, Dakhama A, Haribabu B et al.. (2008) Leukotriene B4 receptor 1 expression on dendritic cells is required for the development of Th2 responses and allergen-induced airway hyperresponsiveness. J Immunol, 181 (2): 1170-8. [PMID:18606670]
42. Miyahara N, Takeda K, Miyahara S, Matsubara S, Koya T, Joetham A, Krishnan E, Dakhama A, Haribabu B, Gelfand EW. (2005) Requirement for leukotriene B4 receptor 1 in allergen-induced airway hyperresponsiveness. Am J Respir Crit Care Med, 172 (2): 161-7. [PMID:15849325]
43. Miyahara N, Takeda K, Miyahara S, Taube C, Joetham A, Koya T, Matsubara S, Dakhama A, Tager AM, Luster AD et al.. (2005) Leukotriene B4 receptor-1 is essential for allergen-mediated recruitment of CD8+ T cells and airway hyperresponsiveness. J Immunol, 174 (8): 4979-84. [PMID:15814727]
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45. Okamoto F, Saeki K, Sumimoto H, Yamasaki S, Yokomizo T. (2010) Leukotriene B4 augments and restores Fc gammaRs-dependent phagocytosis in macrophages. J Biol Chem, 285 (52): 41113-21. [PMID:20959460]
46. Okuno T, Ago H, Terawaki K, Miyano M, Shimizu T, Yokomizo T. (2003) Helix 8 of the leukotriene B4 receptor is required for the conformational change to the low affinity state after G-protein activation. J Biol Chem, 278 (42): 41500-9. [PMID:12902330]
47. Oyoshi MK, He R, Li Y, Mondal S, Yoon J, Afshar R, Chen M, Lee DM, Luo HR, Luster AD et al.. (2012) Leukotriene B4-driven neutrophil recruitment to the skin is essential for allergic skin inflammation. Immunity, 37 (4): 747-58. [PMID:23063331]
48. Richards IM, Sun FF, Taylor BM, Shields SK, Griffin RL, Morris J, Wishka DG, Smith HW, Johnson RA, Dunn CJ. (1991) Contribution of leukotriene B4 to airway inflammation and the effect of antagonists. Ann N Y Acad Sci, 629: 274-87. [PMID:1659282]
49. Runarsson G, Liu A, Mahshid Y, Feltenmark S, Pettersson A, Klein E, Björkholm M, Claesson HE. (2005) Leukotriene B4 plays a pivotal role in CD40-dependent activation of chronic B lymphocytic leukemia cells. Blood, 105 (3): 1274-9. [PMID:15454480]
50. Sabirsh A, Bristulf J, Owman C. (2004) Exploring the pharmacology of the leukotriene B4 receptor BLT1, without the confounding effects of BLT2. Eur J Pharmacol, 499 (1-2): 53-65. [PMID:15363951]
51. Sadik CD, Kim ND, Iwakura Y, Luster AD. (2012) Neutrophils orchestrate their own recruitment in murine arthritis through C5aR and FcγR signaling. Proc Natl Acad Sci USA, 109 (46): E3177-85. [PMID:23112187]
52. Saeki K, Yokomizo T. (2017) Identification, signaling, and functions of LTB4 receptors. Semin Immunol, 33: 30-36. [PMID:29042026]
53. Serezani CH, Aronoff DM, Sitrin RG, Peters-Golden M. (2009) FcgammaRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions. Blood, 114 (15): 3316-24. [PMID:19657115]
54. Shao WH, Del Prete A, Bock CB, Haribabu B. (2006) Targeted disruption of leukotriene B4 receptors BLT1 and BLT2: a critical role for BLT1 in collagen-induced arthritis in mice. J Immunol, 176 (10): 6254-61. [PMID:16670336]
55. Showell HJ, Conklyn MJ, Alpert R, Hingorani GP, Wright KF, Smith MA, Stam E, Salter ED, Scampoli DN, Meltzer S et al.. (1998) The preclinical pharmacological profile of the potent and selective leukotriene B4 antagonist CP-195543. J Pharmacol Exp Ther, 285 (3): 946-54. [PMID:9618393]
56. Showell HJ, Pettipher ER, Cheng JB, Breslow R, Conklyn MJ, Farrell CA, Hingorani GP, Salter ED, Hackman BC, Wimberly DJ. (1995) The in vitro and in vivo pharmacologic activity of the potent and selective leukotriene B4 receptor antagonist CP-105696. J Pharmacol Exp Ther, 273 (1): 176-84. [PMID:7714764]
57. Stanke-Labesque F, Pépin JL, de Jouvencel T, Arnaud C, Baguet JP, Petri MH, Tamisier R, Jourdil JF, Lévy P, Bäck M. (2012) Leukotriene B4 pathway activation and atherosclerosis in obstructive sleep apnea. J Lipid Res, 53 (9): 1944-51. [PMID:22761257]
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