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Target has curated data in GtoImmuPdb
Target id: 120
Nomenclature: GPR84
Family: Class A Orphans
This receptor has a proposed ligand; see the Latest Pairings page for more information.
Gene and Protein Information | ||||||
class A G protein-coupled receptor | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 7 | 396 | 12q13.13 | GPR84 | G protein-coupled receptor 84 | 17 |
Mouse | 7 | 396 | 15 F3 | Gpr84 | G protein-coupled receptor 84 | |
Rat | 7 | 396 | 7q36 | Gpr84 | G protein-coupled receptor 84 |
Previous and Unofficial Names |
GPCR4 | Inflammation-related G-protein coupled receptor EX33 |
Database Links | |
Specialist databases | |
GPCRdb | gpr84_human (Hs), gpr84_mouse (Mm) |
Other databases | |
Alphafold | Q9NQS5 (Hs), Q8CIM5 (Mm) |
ChEMBL Target | CHEMBL3714079 (Hs), CHEMBL4523386 (Mm) |
Ensembl Gene | ENSG00000139572 (Hs), ENSMUSG00000063234 (Mm), ENSRNOG00000036834 (Rn) |
Entrez Gene | 53831 (Hs), 80910 (Mm), 688730 (Rn) |
Human Protein Atlas | ENSG00000139572 (Hs) |
KEGG Gene | hsa:53831 (Hs), mmu:80910 (Mm), rno:688730 (Rn) |
OMIM | 606383 (Hs) |
Pharos | Q9NQS5 (Hs) |
RefSeq Nucleotide | NM_020370 (Hs), NM_030720 (Mm), NM_001109509 (Rn) |
RefSeq Protein | NP_065103 (Hs), NP_109645 (Mm), NP_001102979 (Rn) |
UniProtKB | Q9NQS5 (Hs), Q8CIM5 (Mm) |
Wikipedia | GPR84 (Hs) |
Natural/Endogenous Ligands |
Medium-chain-length fatty acids |
Comments: Medium chain free fatty acids with carbon chain lengths of 9-14 have been shown by several groups to activate GPR84 [11-12,14]. A surrogate ligand for GPR84, 6-n-octylaminouracil, has also been proposed [12]. |
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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Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Medium chain free fatty acids with carbon chain lengths of 9-14 activate GPR84 [12,14]. A surrogate ligand for GPR84, 6-n-octylaminouracil, has also been proposed [12]. |
Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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Immunopharmacology Comments |
GPR84 is proposed as a receptor for free fatty acids. It is predominantly expressed in immune system-related tissues and cells [4] and appears to play an important role in inflammation, immunity, and cancer. Its expression is upregulated under inflammatory conditions (e.g. in LPS-exposed macrophages). GPR84 regulates the production of the pro-inflammatory cytokine IL-12, and thus is involved in the balance of T helper cell responses, and pathological processes in inflammatory diseases [13]. This receptor may provide a direct link between fatty acid metabolism and immune responses [3]. GPR84 agonists are proposed as novel immune response activators as immuno-oncology agents, or could have anti-inflammatory effects mediated via agonist-induced receptor desensitization (functional blockade). Studies in Gpr84 knockout mice indicate that it plays a deleterious role in fibrotic kidney disease models [2]. |
Immuno Process Associations | ||
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Primary Transduction Mechanisms | |
Transducer | Effector/Response |
Gi/Go family | |
References: 14 |
Tissue Distribution | ||||||||
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Expression Datasets | |
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Physiological Functions | ||||||||
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Physiological Consequences of Altering Gene Expression | ||||||||||
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Gene Expression and Pathophysiology Comments | |
In mice suffering from endotoxemia and experimental autoimmune encephalomyelitis (model of multiple sclerosis), microglia express GPR84 in a strong and sustained manner, induced by TNF [1]. |
Biologically Significant Variants | ||||||||||||||||||
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General Comments |
GPR84 expression is induced in macrophages and microglia by LPS [1,14]. The receptor is important for eye development in Xenopus laevis [8]. |
1. Bouchard C, Pagé J, Bédard A, Tremblay P, Vallières L. (2007) G protein-coupled receptor 84, a microglia-associated protein expressed in neuroinflammatory conditions. Glia, 55 (8): 790-800. [PMID:17390309]
2. Gagnon L, Leduc M, Thibodeau JF, Zhang MZ, Grouix B, Sarra-Bournet F, Gagnon W, Hince K, Tremblay M, Geerts L et al.. (2018) A Newly Discovered Antifibrotic Pathway Regulated by Two Fatty Acid Receptors: GPR40 and GPR84. Am J Pathol, 188 (5): 1132-1148. [PMID:29454750]
3. Huang Q, Feng D, Liu K, Wang P, Xiao H, Wang Y, Zhang S, Liu Z. (2014) A medium-chain fatty acid receptor Gpr84 in zebrafish: expression pattern and roles in immune regulation. Dev Comp Immunol, 45 (2): 252-8. [PMID:24704214]
4. Ichimura A, Hirasawa A, Hara T, Tsujimoto G. (2009) Free fatty acid receptors act as nutrient sensors to regulate energy homeostasis. Prostaglandins Other Lipid Mediat, 89 (3-4): 82-8. [PMID:19460454]
5. Labeguere FG, Nwesome GJR, Alvey LJ, Saniere LRM, Fletcher SR. (2013) Novel dihydropyrimidinoisoquinolinones and pharmaceutical compositions thereof for the treatment of inflammatory disorders. Patent number: WO2013092791A1. Assignee: Galapagos Nv. Priority date: 22/12/2011. Publication date: 27/06/2013.
6. Lattin JE, Schroder K, Su AI, Walker JR, Zhang J, Wiltshire T, Saijo K, Glass CK, Hume DA, Kellie S, Sweet MJ. (2008) Expression analysis of G Protein-Coupled Receptors in mouse macrophages. Immunome Res, 4: 5. [PMID:18442421]
7. Marsango S, Barki N, Jenkins L, Tobin AB, Milligan G. (2022) Therapeutic validation of an orphan G protein-coupled receptor: The case of GPR84. Br J Pharmacol, 179 (14): 3529-3541. [PMID:32869860]
8. Perry KJ, Johnson VR, Malloch EL, Fukui L, Wever J, Thomas AG, Hamilton PW, Henry JJ. (2010) The G-protein-coupled receptor, GPR84, is important for eye development in Xenopus laevis. Dev Dyn, 239 (11): 3024-37. [PMID:20925114]
9. Pillaiyar T, Köse M, Namasivayam V, Sylvester K, Borges G, Thimm D, von Kügelgen I, Müller CE. (2018) 6-(Ar)Alkylamino-Substituted Uracil Derivatives: Lipid Mimetics with Potent Activity at the Orphan G Protein-Coupled Receptor 84 (GPR84). ACS Omega, 3 (3): 3365-3383. [PMID:30023867]
10. Simard JC, Thibodeau JF, Leduc M, Tremblay M, Laverdure A, Sarra-Bournet F, Gagnon W, Ouboudinar J, Gervais L, Felton A et al.. (2020) Fatty acid mimetic PBI-4547 restores metabolic homeostasis via GPR84 in mice with non-alcoholic fatty liver disease. Sci Rep, 10 (1): 12778. [PMID:32728158]
11. Southern C, Cook JM, Neetoo-Isseljee Z, Taylor DL, Kettleborough CA, Merritt A, Bassoni DL, Raab WJ, Quinn E, Wehrman TS et al.. (2013) Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors. J Biomol Screen, 18 (5): 599-609. [PMID:23396314]
12. Suzuki M, Takaishi S, Nagasaki M, Onozawa Y, Iino I, Maeda H, Komai T, Oda T. (2013) Medium-chain Fatty Acid-sensing Receptor, GPR84, Is a Proinflammatory Receptor. J Biol Chem, 288 (15): 10684-91. [PMID:23449982]
13. Venkataraman C, Kuo F. (2005) The G-protein coupled receptor, GPR84 regulates IL-4 production by T lymphocytes in response to CD3 crosslinking. Immunol Lett, 101 (2): 144-53. [PMID:15993493]
14. Wang J, Wu X, Simonavicius N, Tian H, Ling L. (2006) Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84. J Biol Chem, 281 (45): 34457-64. [PMID:16966319]
15. Wang P, Raja A, Luscombe VB, Bataille CJR, Lucy D, Rogga VV, Greaves DR, Russell AJ. (2024) Development of Highly Potent, G-Protein Pathway Biased, Selective, and Orally Bioavailable GPR84 Agonists. J Med Chem, 67 (1): 110-137. [PMID:38146625]
16. Wittenberger T, Schaller HC, Hellebrand S. (2001) An expressed sequence tag (EST) data mining strategy succeeding in the discovery of new G-protein coupled receptors. J Mol Biol, 307 (3): 799-813. [PMID:11273702]
17. Yousefi S, Cooper PR, Potter SL, Mueck B, Jarai G. (2001) Cloning and expression analysis of a novel G-protein-coupled receptor selectively expressed on granulocytes. J Leukoc Biol, 69 (6): 1045-52. [PMID:11404393]