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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 | 423 | 2p21 | OXER1 | oxoeicosanoid receptor 1 | 2 |
| Previous and Unofficial Names |
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| hGPCR48 [14] | R527 [13] | TG1019 [9] | GPR170 | 5-oxo-ETE receptor | oxoeicosanoid (OXE) receptor 1 | |
| Database Links |
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| Specialist databases | |
| GPCRdb | oxer1_human (Hs) |
| Other databases | |
| Alphafold | Q8TDS5 (Hs) |
| ChEMBL Target | CHEMBL1628461 (Hs) |
| Ensembl Gene | ENSG00000162881 (Hs) |
| Entrez Gene | 165140 (Hs) |
| Human Protein Atlas | ENSG00000162881 (Hs) |
| KEGG Gene | hsa:165140 (Hs) |
| Pharos | Q8TDS5 (Hs) |
| RefSeq Nucleotide | NM_148962 (Hs) |
| RefSeq Protein | NP_683765 (Hs) |
| UniProtKB | Q8TDS5 (Hs) |
| Wikipedia | OXER1 (Hs) |
| Natural/Endogenous Ligands |
| 5-oxo-C20:3 |
| 5-oxo-ETE |
| 5-oxo-20-HETE |
| 5-oxo-12-HETE |
| 5-oxo-15-HETE |
| 5-oxo-ODE |
| 5S-HETE |
| 5S-HPETE |
| Comments: 5-Oxo-ETE and 5-oxo-C20:3 are the most potent endogenous agonists |
| Potency order of endogenous ligands |
| 5-oxo-ETE, 5-oxo-C20:3, 5-oxo-ODE > 5-oxo-15-HETE > 5S-HPETE > 5S-HETE [8-9,13,25-26,33,37] |
Download all structure-activity data for this target as a CSV file 
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| There are some discrepancies in the relative potencies of 5-oxo-ETE vs 5-oxo-15-HETE (5-oxo-ETE more potent [21,32]; equipotent [37]). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Allosteric Modulators | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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| Allosteric Modulator Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Gue1654 inhibits most responses to 5-oxo-ETE (mediated by blocking Gβγ signalling) but not Gαi-mediated inhibition of adenylyl cyclase [1]. | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Immunopharmacology Comments |
| Activation of oxoeicosanoid receptor, OXER1, by products of 5-lipoxygenase enzyme activity has downstream effects on inflammation and immunity [8]. The OXER1 agonist 5-oxo-ETE acts as a chemoattractant for eosinophils [35] (e.g. in asthmatic airways [12]) and basophils [40]. OXER1 antagonists are being investigated for potential in eosinophilic diseases such as allergic rhinitis and asthma [27] |
| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gi/Go family | Phospholipase C stimulation |
| References: 1,10 | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
| Gi/Go family |
Adenylyl cyclase inhibition Phospholipase A2 stimulation Other - See Comments |
| Comments: Stimulation of PI3K [10,19], ERK [10,15,22] and p38 [15] MAP kinases. | |
| References: 1,9-10,22 | |
| Tissue Distribution
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| Functional Assays
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| Functional Assay Comments | ||||||||||
| 5-oxo-ETE-induced degranulation is modest unless cells are pretreated with cytokines (G-CSF or GM-CSF). |
| Physiological Functions
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| Physiological Functions Comments | ||||||||
| To undergo the respiratory burst in response to 5-oxo-ETE neutrophils must first be pretreated with cytokines (G-CSF or GM-CSF) [22]. | ||||||||
| Physiological Consequences of Altering Gene Expression Comments | |
| Since there is no ortholog of OXER1 in mice, gene knockout studies cannot be done in this species. |
| Biologically Significant Variants
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| General Comments |
| There are no mouse or rat orthologues of OXER1. |
1. Blättermann S, Peters L, Ottersbach PA, Bock A, Konya V, Weaver CD, Gonzalez A, Schröder R, Tyagi R, Luschnig P et al.. (2012) A biased ligand for OXE-R uncouples Gα and Gβγ signaling within a heterotrimer. Nat Chem Biol, 8 (7): 631-8. [PMID:22634634]
2. Brink C, Dahlén SE, Drazen J, Evans JF, Hay DW, Rovati GE, Serhan CN, Shimizu T, Yokomizo T. (2004) International Union of Pharmacology XLIV. Nomenclature for the oxoeicosanoid receptor. Pharmacol Rev, 56 (1): 149-57. [PMID:15001665]
3. Cooke M, Di Cónsoli H, Maloberti P, Cornejo Maciel F. (2013) Expression and function of OXE receptor, an eicosanoid receptor, in steroidogenic cells. Mol Cell Endocrinol, 371 (1-2): 71-8. [PMID:23159987]
4. Cossette C, Patel P, Anumolu JR, Sivendran S, Lee GJ, Gravel S, Graham FD, Lesimple A, Mamer OA, Rokach J et al.. (2008) Human neutrophils convert the sebum-derived polyunsaturated fatty acid Sebaleic acid to a potent granulocyte chemoattractant. J Biol Chem, 283 (17): 11234-43. [PMID:18287092]
5. Czech W, Barbisch M, Tenscher K, Schöpf E, Schröder JM, Norgauer J. (1997) Chemotactic 5-oxo-eicosatetraenoic acids induce oxygen radical production, Ca2+-mobilization, and actin reorganization in human eosinophils via a pertussis toxin-sensitive G-protein. J Invest Dermatol, 108 (1): 108-12. [PMID:8980298]
6. Dallaire MJ, Ferland C, Pagé N, Lavigne S, Davoine F, Laviolette M. (2003) Endothelial cells modulate eosinophil surface markers and mediator release. Eur Respir J, 21 (6): 918-24. [PMID:12797482]
7. Gore V, Patel P, Chang CT, Sivendran S, Kang N, Ouedraogo YP, Gravel S, Powell WS, Rokach J. (2013) 5-Oxo-ETE receptor antagonists. J Med Chem, 56 (9): 3725-32. [PMID:23581530]
8. Grant GE, Rokach J, Powell WS. (2009) 5-Oxo-ETE and the OXE receptor. Prostaglandins Other Lipid Mediat, 89 (3-4): 98-104. [PMID:19450703]
9. Hosoi T, Koguchi Y, Sugikawa E, Chikada A, Ogawa K, Tsuda N, Suto N, Tsunoda S, Taniguchi T, Ohnuki T. (2002) Identification of a novel human eicosanoid receptor coupled to G(i/o). J Biol Chem, 277 (35): 31459-65. [PMID:12065583]
10. Hosoi T, Sugikawa E, Chikada A, Koguchi Y, Ohnuki T. (2005) TG1019/OXE, a Galpha(i/o)-protein-coupled receptor, mediates 5-oxo-eicosatetraenoic acid-induced chemotaxis. Biochem Biophys Res Commun, 334 (4): 987-95. [PMID:16039985]
11. Iikura M, Suzukawa M, Yamaguchi M, Sekiya T, Komiya A, Yoshimura-Uchiyama C, Nagase H, Matsushima K, Yamamoto K, Hirai K. (2005) 5-Lipoxygenase products regulate basophil functions: 5-Oxo-ETE elicits migration, and leukotriene B(4) induces degranulation. J Allergy Clin Immunol, 116 (3): 578-85. [PMID:16159627]
12. Jones CE. (2005) The OXE receptor: a new therapeutic approach for asthma?. Trends Mol Med, 11 (6): 266-70. [PMID:15949767]
13. Jones CE, Holden S, Tenaillon L, Bhatia U, Seuwen K, Tranter P, Turner J, Kettle R, Bouhelal R, Charlton S, Nirmala NR, Jarai G, Finan P. (2003) Expression and characterization of a 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid receptor highly expressed on human eosinophils and neutrophils. Mol Pharmacol, 63: 471-477. [PMID:12606753]
14. Koike D, Obinata H, Yamamoto A, Takeda S, Komori H, Nara F, Izumi T, Haga T. (2006) 5-Oxo-eicosatetraenoic acid-induced chemotaxis: identification of a responsible receptor hGPCR48 and negative regulation by G protein G(12/13). J Biochem, 139 (3): 543-9. [PMID:16567419]
15. Langlois A, Chouinard F, Flamand N, Ferland C, Rola-Pleszczynski M, Laviolette M. (2009) Crucial implication of protein kinase C (PKC)-delta, PKC-zeta, ERK-1/2, and p38 MAPK in migration of human asthmatic eosinophils. J Leukoc Biol, 85 (4): 656-63. [PMID:19164129]
16. Lasky-Su J, Neale BM, Franke B, Anney RJ, Zhou K, Maller JB, Vasquez AA, Chen W, Asherson P, Buitelaar J et al.. (2008) Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. Am J Med Genet B Neuropsychiatr Genet, 147B (8): 1345-54. [PMID:18821565]
17. Monneret G, Boumiza R, Gravel S, Cossette C, Bienvenu J, Rokach J, Powell WS. (2005) Effects of prostaglandin D(2) and 5-lipoxygenase products on the expression of CD203c and CD11b by basophils. J Pharmacol Exp Ther, 312 (2): 627-34. [PMID:15388786]
18. Muro S, Hamid Q, Olivenstein R, Taha R, Rokach J, Powell WS. (2003) 5-oxo-6,8,11,14-eicosatetraenoic acid induces the infiltration of granulocytes into human skin. J Allergy Clin Immunol, 112 (4): 768-74. [PMID:14564360]
19. Norgauer J, Barbisch M, Czech W, Pareigis J, Schwenk U, Schröder JM. (1996) Chemotactic 5-oxo-icosatetraenoic acids activate a unique pattern of neutrophil responses. Analysis of phospholipid metabolism, intracellular Ca2+ transients, actin reorganization, superoxide-anion production and receptor up-regulation. Eur J Biochem, 236 (3): 1003-9. [PMID:8665888]
20. O'Flaherty JT, Cordes J, Redman J, Thomas MJ. (1993) 5-Oxo-eicosatetraenoate, a potent human neutrophil stimulus. Biochem Biophys Res Commun, 192 (1): 129-34. [PMID:8386504]
21. O'Flaherty JT, Cordes JF, Lee SL, Samuel M, Thomas MJ. (1994) Chemical and biological characterization of oxo-eicosatetraenoic acids. Biochim Biophys Acta, 1201 (3): 505-15. [PMID:7803484]
22. O'Flaherty JT, Kuroki M, Nixon AB, Wijkander J, Yee E, Lee SL, Smitherman PK, Wykle RL, Daniel LW. (1996) 5-Oxo-eicosanoids and hematopoietic cytokines cooperate in stimulating neutrophil function and the mitogen-activated protein kinase pathway. J Biol Chem, 271 (30): 17821-8. [PMID:8663432]
23. O'Flaherty JT, Kuroki M, Nixon AB, Wijkander J, Yee E, Lee SL, Smitherman PK, Wykle RL, Daniel LW. (1996) 5-Oxo-eicosatetraenoate is a broadly active, eosinophil-selective stimulus for human granulocytes. J Immunol, 157 (1): 336-42. [PMID:8683135]
24. O'Flaherty JT, Rogers LC, Paumi CM, Hantgan RR, Thomas LR, Clay CE, High K, Chen YQ, Willingham MC, Smitherman PK et al.. (2005) 5-Oxo-ETE analogs and the proliferation of cancer cells. Biochim Biophys Acta, 1736 (3): 228-36. [PMID:16154383]
25. O'Flaherty JT, Taylor JS, Thomas MJ. (1998) Receptors for the 5-oxo class of eicosanoids in neutrophils. J Biol Chem, 273 (49): 32535-41. [PMID:9829988]
26. Patel P, Cossette C, Anumolu JR, Gravel S, Lesimple A, Mamer OA, Rokach J, Powell WS. (2008) Structural requirements for activation of the 5-oxo-6E,8Z, 11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) receptor: identification of a mead acid metabolite with potent agonist activity. J Pharmacol Exp Ther, 325 (2): 698-707. [PMID:18292294]
27. Patel P, Reddy CN, Gore V, Chourey S, Ye Q, Ouedraogo YP, Gravel S, Powell WS, Rokach J. (2014) Two Potent OXE-R Antagonists: Assignment of Stereochemistry. ACS Med Chem Lett, 5 (7): 815-9. [PMID:25050171]
28. Powell WS, Chung D, Gravel S. (1995) 5-Oxo-6,8,11,14-eicosatetraenoic acid is a potent stimulator of human eosinophil migration. J Immunol, 154 (8): 4123-32. [PMID:7706749]
29. Powell WS, Gravel S, Halwani F. (1999) 5-oxo-6,8,11,14-eicosatetraenoic acid is a potent stimulator of L-selectin shedding, surface expression of CD11b, actin polymerization, and calcium mobilization in human eosinophils. Am J Respir Cell Mol Biol, 20 (1): 163-70. [PMID:9870930]
30. Powell WS, Gravel S, Halwani F, Hii CS, Huang ZH, Tan AM, Ferrante A. (1997) Effects of 5-oxo-6,8,11,14-eicosatetraenoic acid on expression of CD11b, actin polymerization, and adherence in human neutrophils. J Immunol, 159 (6): 2952-9. [PMID:9300719]
31. Powell WS, Gravel S, Khanapure SP, Rokach J. (1999) Biological inactivation of 5-oxo-6,8,11,14-eicosatetraenoic acid by human platelets. Blood, 93 (3): 1086-96. [PMID:9920859]
32. Powell WS, Gravel S, MacLeod RJ, Mills E, Hashefi M. (1993) Stimulation of human neutrophils by 5-oxo-6,8,11,14-eicosatetraenoic acid by a mechanism independent of the leukotriene B4 receptor. J Biol Chem, 268 (13): 9280-6. [PMID:8387490]
33. Powell WS, Gravelle F, Gravel S. (1992) Metabolism of 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid and other 5(S)-hydroxyeicosanoids by a specific dehydrogenase in human polymorphonuclear leukocytes. J Biol Chem, 267 (27): 19233-41. [PMID:1326548]
34. Powell WS, MacLeod RJ, Gravel S, Gravelle F, Bhakar A. (1996) Metabolism and biologic effects of 5-oxoeicosanoids on human neutrophils. J Immunol, 156 (1): 336-42. [PMID:8598482]
35. Powell WS, Rokach J. (2013) The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor. Prog Lipid Res, 52 (4): 651-65. [PMID:24056189]
36. Sarveswaran S, Ghosh J. (2013) OXER1, a G protein-coupled oxoeicosatetraenoid receptor, mediates the survival-promoting effects of arachidonate 5-lipoxygenase in prostate cancer cells. Cancer Lett, 336 (1): 185-95. [PMID:23643940]
37. Schwenk U, Schröder JM. (1995) 5-Oxo-eicosanoids are potent eosinophil chemotactic factors. Functional characterization and structural requirements. J Biol Chem, 270 (25): 15029-36. [PMID:7797484]
38. Sozzani S, Zhou D, Locati M, Bernasconi S, Luini W, Mantovani A, O'Flaherty JT. (1996) Stimulating properties of 5-oxo-eicosanoids for human monocytes: synergism with monocyte chemotactic protein-1 and -3. J Immunol, 157 (10): 4664-71. [PMID:8906847]
39. Stamatiou PB, Chan CC, Monneret G, Ethier D, Rokach J, Powell WS. (2004) 5-oxo-6,8,11,14-eicosatetraenoic acid stimulates the release of the eosinophil survival factor granulocyte/macrophage colony-stimulating factor from monocytes. J Biol Chem, 279 (27): 28159-64. [PMID:15136573]
40. Sturm GJ, Schuligoi R, Sturm EM, Royer JF, Lang-Loidolt D, Stammberger H, Amann R, Peskar BA, Heinemann A. (2005) 5-Oxo-6,8,11,14-eicosatetraenoic acid is a potent chemoattractant for human basophils. J Allergy Clin Immunol, 116 (5): 1014-9. [PMID:16275369]
41. Sundaram S, Ghosh J. (2006) Expression of 5-oxoETE receptor in prostate cancer cells: critical role in survival. Biochem Biophys Res Commun, 339 (1): 93-8. [PMID:16289380]
42. Urasaki T, Takasaki J, Nagasawa T, Ninomiya H. (2001) Pivotal role of 5-lipoxygenase in the activation of human eosinophils: platelet-activating factor and interleukin-5 induce CD69 on eosinophils through the 5-lipoxygenase pathway. J Leukoc Biol, 69 (1): 105-12. [PMID:11200053]
43. Ye Q, Chourey S, Reddy CN, Wang R, Cossette C, Gravel S, Slobodchikova I, Vuckovic D, Rokach J, Powell WS. (2020) Novel highly potent OXE receptor antagonists with prolonged plasma lifetimes that are converted to active metabolites in vivo in monkeys. Br J Pharmacol, 177 (2): 388-401. [PMID:31655025]
target has curated data in GtoImmuPdb
