GPR84

Target id: 120

Nomenclature: GPR84

Family: Class A Orphans

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

This receptor has a proposed ligand; see the Latest Pairings page for more information.

   GtoImmuPdb view: OFF :     Currently no data for GPR84 in GtoImmuPdb

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 10
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
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
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 [5-6,8]. A surrogate ligand for GPR84, 6-n-octylaminouracil, has also been proposed [6].

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
Ligand Sp. Action Affinity Units Reference
6-n-octylaminouracil Hs Full agonist 7.0 pEC50 6
pEC50 7.0 (EC50 1.05x10-7 M) [6]
decanoic acid Hs Full agonist 5.0 – 5.4 pEC50 5,8
pEC50 5.0 – 5.4 [5,8]
undecanoic acid Hs Agonist 5.1 pEC50 8
pEC50 5.1 (EC50 8x10-6 M) [8]
lauric acid Hs Agonist 5.1 pEC50 8
pEC50 5.1 (EC50 9x10-6 M) [8]
2-hydroxylauric acid Hs Full agonist 5.0 pEC50 6
pEC50 5.0 (EC50 9.9x10-6 M) [6]
3-hydroxylauric acid Hs Full agonist 4.9 pEC50 6
pEC50 4.9 (EC50 1.3x10-5 M) [6]
2-hydroxy capric acid Hs Full agonist 4.5 pEC50 6
pEC50 4.5 (EC50 3.1x10-5 M) [6]
3-hydroxy capric acid Hs Full agonist 3.6 pEC50 6
pEC50 3.6 (EC50 2.3x10-4 M) [6]
Agonist Comments
Medium chain free fatty acids with carbon chain lengths of 9-14 activate GPR84 [6,8]. A surrogate ligand for GPR84, 6-n-octylaminouracil, has also been proposed [6].
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
References:  8
Tissue Distribution
Bone marrow, lung, peripheral blood leukocytes
Species:  Human
Technique:  Northern blot
References:  10
Neutrophils, eosinophils
Species:  Human
Technique:  RT-PCR
References:  10
Brain (medulla, substantia nigra, thalamus, corpus callosum), spinal cord, heart, colon, thymus, spleen, kidney, liver, intestine, placenta, lung, leukocytes
Species:  Human
Technique:  Northern blot
References:  9
Bone marrow, spleen, lung, testis, peritoneal macrophages
Species:  Mouse
Technique:  RT-PCR
References:  7-8
Spleen, liver
Species:  Mouse
Technique:  Northern blot
References:  9
Primary non-inflammatory macrophages
Species:  Mouse
Technique:  Microarray analysis
References:  3
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Physiological Functions
Medium chain free fatty acids amplify lipopolysaccharide-stimulated production of IL-12 p40 through GPR84
Species:  Human
Tissue:  Leukocytes
References:  2,7
Physiological Consequences of Altering Gene Expression
Primary stimulation of T cells with anti-CD3 resulted in increased IL-4 production in GPR84 knockout mice. Th2 effector cells from knockout mice produce higher levels of IL-4, IL-5 and IL-13
Species:  Mouse
Tissue:  T cells
Technique:  Gene knockouts
References:  7
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
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  G37D
Global MAF (%):  1
Subpopulation MAF (%):  ASN: 4
Minor allele count:  T=0.011/25
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  1000 Genomes, HapMap
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  W370H
Global MAF (%):  1
Subpopulation MAF (%):  ASN: 4
Minor allele count:  G=0.011/23
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  1000 Genomes, Frequency
General Comments
GPR84 expression is induced in macrophages and microglia by LPS [1,8]. The receptor is important for eye development in Xenopus laevis [4].

References

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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. Glia55 (8): 790-800. [PMID:17390309]

2. 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]

3. 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 Res4: 5. [PMID:18442421]

4. 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]

5. 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 Screen18 (5): 599-609. [PMID:23396314]

6. 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]

7. 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]

8. 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 Chem281: 34457-34464. [PMID:16966319]

9. 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]

10. 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]

Contributors

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How to cite this page

Anthony P. Davenport, Stephen Alexander, Joanna L. Sharman, Adam J. Pawson, Helen E. Benson, Amy E. Monaghan, Wen Chiy Liew, Chido Mpamhanga, Jim Battey, Richard V. Benya, Robert T. Jensen, Sadashiva Karnik, Evi Kostenis, Eliot Spindel, Laura Storjohann, Kalyan Tirupula, Tom I. Bonner, Richard Neubig, Jean-Philippe Pin, Michael Spedding, Anthony Harmar.
Class A Orphans: GPR84. Last modified on 30/07/2015. Accessed on 19/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=120.