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GPR83

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Target id: 119

Nomenclature: GPR83

Family: Class A Orphans with emerging pharmacology

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 423 11q21 GPR83 G protein-coupled receptor 83 3,15
Mouse 7 423 9 4.4 cM Gpr83 G protein-coupled receptor 83 3,10
Rat 7 422 8q11 Gpr83 G protein-coupled receptor 83 21
Previous and Unofficial Names Click here for help
GIR | GPR72 | glucocorticoid induced receptor | G protein-coupled receptor 72 | JP05 [2]
Database Links Click here for help
Specialist databases
GPCRdb gpr83_human (Hs), gpr83_mouse (Mm)
Other databases
Alphafold Q9NYM4 (Hs), P30731 (Mm)
ChEMBL Target CHEMBL4523924 (Hs)
Ensembl Gene ENSG00000123901 (Hs), ENSMUSG00000031932 (Mm), ENSRNOG00000030318 (Rn)
Entrez Gene 10888 (Hs), 14608 (Mm), 140595 (Rn)
Human Protein Atlas ENSG00000123901 (Hs)
KEGG Gene hsa:10888 (Hs), mmu:14608 (Mm), rno:140595 (Rn)
OMIM 605569 (Hs)
Pharos Q9NYM4 (Hs)
RefSeq Nucleotide NM_016540 (Hs), NM_010287 (Mm), NM_080411 (Rn)
RefSeq Protein NP_057624 (Hs), NP_034417 (Mm)
UniProtKB Q9NYM4 (Hs), P30731 (Mm)
Wikipedia GPR83 (Hs)

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PEN {Sp: Rat} Peptide Mm Agonist 8.1 pKd 7
⤷ pKd 8.1 (Kd 8x10-9 M) [7]
Description: N-terminally tyrosinated radioidodinated rPEN binding to mouse GPR83 in hypothalamic membrane preparations.
PEN {Sp: Mouse} Peptide Mm Agonist 7.0 – 10.7 pEC50 7
⤷ pEC50 10.7 (EC50 1.8x10-11 M) [7]
Description: High affinity binding site of mouse GPR83
pEC50 7.0 (EC50 1.1x10-7 M) [7]
Description: Low affinity binding site of mouse GPR83
Zn2+ Click here for species-specific activity table Mm Full agonist 5.0 pEC50 14
⤷ pEC50 5.0 (EC50 1.02x10-5 M) [14]
Agonist Comments
It is reported that rat GPR83 can bind to neuropeptide Y fragments [17].
Tissue Distribution Click here for help
High expression was detected in the cerebral cortex (layer II), hippocampus (pyramidal CA3 neurons and granule cells), amygdala (basal and periamygdaloid cortical nuclei), in the endopiriform nucleus, diagonal band of Broca, thalamus (nucleus reuniens, parafascicular nucleus) and hypothalamus (posterior, dorsal and around the medial mammillary nuclei). Low expression was detected in the deeper cortical layers, raphe and throughout the striatum.
Species:  Human
Technique:  In situ hybridisation
References:  2
Lymphoid cells
Species:  Mouse
Technique:  RNase protection assay
References:  10
Brain
Species:  Mouse
Technique:  Northern blot
References:  2,15
CD8+Foxp3+T cells
Species:  Mouse
Technique:  Microarray analysis
References:  6
Extensively distributed throughout the rostrocaudal extention of the brain and spinal cord, with high to moderate level of GPR83 mRNA localised in the forebrain (primarily within limbic system structures, the dorsal and ventral striatum and in some hypothalamic nuclei)
Species:  Mouse
Technique:  In situ hybridisation
References:  20
Highly expressed in the olfactory tubercle, nucleus accumbens, striatum, amygdala, hippocampus, hypothalamus and, to a lesser extent, areas of the cerebral cortex.
Species:  Mouse
Technique:  In situ hybridisation
References:  1,16
CD4+ and CD25+ regulatory T cells in spleen and lymph node cells
Species:  Mouse
Technique:  Immunohistochemistry
References:  19
Warm sensitive neurons of the preoptic areas of the anterior hypothalamus
Species:  Mouse
Technique:  Microarray analysis
References:  5
Highly expressed in scattered hippocampal neurons, the nucleus of the lateral olfactory tract and midline thalamic nuclei. Positive signal was also observed in the dorsolateral septum and tenia tecta, all regions of neocortex, limbic cortical regions, olfactory bulbs, posterior divisions of the bed of nucleus of the stria terminalis, and the ventromedial and ventrobasal complexes of the thalamus. Low level of mRNA was detected in neuroendocrine regulatory regions of the hypothalamus and nucleus accumbens shell.
Species:  Rat
Technique:  In situ hybridisation
References:  21
Brain. High levels of GPR83 mRNA were observed in forebrain limbic and thalamic structures, including layers 2 and 3 of the nucleus of the lateral olfactory tract, hippocampal interneurons, nucleus reunions of the thalamus and the medial mammillary nuclei. Moderate to lower levels of GPR83 mRNA is observed in neocortical mantle, striatum, multiple amygdaloid nuclei, ventromedial hypothalamic nucleus, arcuate nucleus, lateral hypothalamus and some cranial nerve nuclei of the brainstem.
Species:  Rat
Technique:  In situ hybridisation
References:  18
Brain. Not detected in heart, spleen, lung, liver, skeletal muscle, kidney and testis
Species:  Rat
Technique:  Northern blot
References:  21
Tissue Distribution Comments
A notable difference in GPR83 expression is observed in mouse and rat, especially the differential distribution of GPR83 in striatum and cortex [21].

GPR83 mRNA levels are upregulated persistently in rat prefrontal cortex following chronic amphetamine asministration, suggesting a role for GPR83 in dopaminergic neuroadaptation [21].

Significant decrease of GPR83 expression is found in striatum, nucleus accumbens, olfactory tubercle, CA2 sub-region of the hippocampus and hypothalamic nuclei following acute dexamethasone treatment [1].

GPR83 is upregulated in AGS cells by Helicobacter pylori adhesion [12].

Upon n-3 PUFA-depletion in rat, the expression of GPR83 mRNA in olfactory bulb decreased significantly, whereas no change in GPR83 expression was observed in neocortex and piriform cortex [11]. Rats that were not deprived of n-3 PUFA showed a significant increase in GPR83 mRNA expression in neocortex and olfactory bulb [11].
Expression Datasets Click here for help

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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 Comments
A study by Hansen et al. showed that GPR83 overexpression in naïve Foxp3- regulatory T cells led to the induction of Foxp3+ cells during inflammatory conditions in vivo [8]. However, two studies demonstrated that GPR83 is dispensable for regulatory T cell development and function [13,20]. Hansen et al. later reported that mouse GPR83 isoform-4 is involved in the induction of regulatory T cells during inflammation [9].
Physiological Consequences of Altering Gene Expression Click here for help
GPR83-transduced T cells inhibit the effector phase of a severe contact hypersensitivity reaction of the skin.
Species:  Mouse
Tissue:  T cells
Technique:  Retroviral transduction
References:  8
Mice with GPR83 knockdown show a small but significant reduction of core body temperature (0.15°C) during the dark/active cycle of the day, increased body weight and increased level of circulating adiponectin. This suggests that GPR83 may involve in central thermoregulation and the control of circulating adiponectin.
Species:  Mouse
Tissue:  Hypothalamic preoptic area
Technique:  RNA interference (RNAi)
References:  4
Physiological Consequences of Altering Gene Expression Comments
It is reported that mice deficient in GPR83 expression were normal and did not have signs of inflammatory disease [20].
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Gpr83tm1.1Fpow Gpr83tm1.1Fpow/Gpr83tm1.1Fpow
C.129-Gpr83		 MGI:95712  MP:0008075 decreased CD4-positive T cell number PMID: 18479351 
Gpr83tm1.1Ayr Gpr83tm1.1Ayr/Gpr83tm1.1Ayr
involves: 129 * BALB/c		 MGI:95712  MP:0002169 no abnormal phenotype detected PMID: 17893329 
Gpr83tm1.1Fpow Gpr83tm1.1Fpow/Gpr83tm1.1Fpow
C.129-Gpr83		 MGI:95712  MP:0000693 spleen hyperplasia PMID: 18479351 
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  P374Q
Global MAF (%):  8
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 3|7|10|9
Minor allele count:  T=0.077/168
SNP accession:  VAR_047079, rs3740868
Validation:  1000 Genomes, HapMap
General Comments
Four different GPR83 isoforms have been described in mice but only isoform-1 has been described in humans [4].

References

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1. Adams F, Grassie M, Shahid M, Hill DR, Henry B. (2003) Acute oral dexamethasone administration reduces levels of orphan GPCR glucocorticoid-induced receptor (GIR) mRNA in rodent brain: potential role in HPA-axis function. Brain Res Mol Brain Res, 117 (1): 39-46. [PMID:14499479]

2. Brézillon S, Detheux M, Parmentier M, Hökfelt T, Hurd YL. (2001) Distribution of an orphan G-protein coupled receptor (JP05) mRNA in the human brain. Brain Res, 921 (1-2): 21-30. [PMID:11720708]

3. De Moerlooze L, Williamson J, Liners F, Perret J, Parmentier M. (2000) Cloning and chromosomal mapping of the mouse and human genes encoding the orphan glucocorticoid-induced receptor (GPR83). Cytogenet Cell Genet, 90 (1-2): 146-50. [PMID:11060465]

4. Dubins JS, Sanchez-Alavez M, Zhukov V, Sanchez-Gonzalez A, Moroncini G, Carvajal-Gonzalez S, Hadcock JR, Bartfai T, Conti B. (2012) Downregulation of GPR83 in the hypothalamic preoptic area reduces core body temperature and elevates circulating levels of adiponectin. Metab Clin Exp, 61 (10): 1486-93. [PMID:22560055]

5. Eberwine J, Bartfai T. (2011) Single cell transcriptomics of hypothalamic warm sensitive neurons that control core body temperature and fever response Signaling asymmetry and an extension of chemical neuroanatomy. Pharmacol Ther, 129 (3): 241-59. [PMID:20970451]

6. Fleissner D, Frede A, Knott M, Knuschke T, Geffers R, Hansen W, Dobos G, Langhorst J, Buer J, Westendorf AM. (2011) Generation and function of immunosuppressive human and murine CD8+ T cells by transforming growth factor-β and retinoic acid. Immunology, 134 (1): 82-92. [PMID:21711349]

7. Gomes I, Bobeck EN, Margolis EB, Gupta A, Sierra S, Fakira AK, Fujita W, Müller TD, Müller A, Tschöp MH et al.. (2016) Identification of GPR83 as the receptor for the neuroendocrine peptide PEN. Sci Signal, 9 (425): ra43. [PMID:27117253]

8. Hansen W, Loser K, Westendorf AM, Bruder D, Pfoertner S, Siewert C, Huehn J, Beissert S, Buer J. (2006) G protein-coupled receptor 83 overexpression in naive CD4+CD25- T cells leads to the induction of Foxp3+ regulatory T cells in vivo. J Immunol, 177 (1): 209-15. [PMID:16785516]

9. Hansen W, Westendorf AM, Toepfer T, Mauel S, Geffers R, Gruber AD, Buer J. (2010) Inflammation in vivo is modulated by GPR83 isoform-4 but not GPR83 isoform-1 expression in regulatory T cells. Genes Immun, 11 (4): 357-61. [PMID:20200545]

10. Harrigan MT, Campbell NF, Bourgeois S. (1991) Identification of a gene induced by glucocorticoids in murine T-cells: a potential G protein-coupled receptor. Mol Endocrinol, 5 (9): 1331-8. [PMID:1663214]

11. Hichami A, Datiche F, Ullah S, Liénard F, Chardigny JM, Cattarelli M, Khan NA. (2007) Olfactory discrimination ability and brain expression of c-fos, Gir and Glut1 mRNA are altered in n-3 fatty acid-depleted rats. Behav Brain Res, 184 (1): 1-10. [PMID:17686536]

12. Kim N, Park WY, Kim JM, Park YS, Lee DH, Park JH, Kim JS, Jung HC, Song IS. (2007) Analysis of Gene Expression Profile of AGS Cells Stimulated by Helicobacter pylori Adhesion. Gut Liver, 1 (1): 40-8. [PMID:20485657]

13. Lu LF, Gavin MA, Rasmussen JP, Rudensky AY. (2007) G protein-coupled receptor 83 is dispensable for the development and function of regulatory T cells. Mol Cell Biol, 27 (23): 8065-72. [PMID:17893329]

14. Müller A, Kleinau G, Piechowski CL, Müller TD, Finan B, Pratzka J, Grüters A, Krude H, Tschöp M, Biebermann H. (2013) G-protein coupled receptor 83 (GPR83) signaling determined by constitutive and zinc(II)-induced activity. PLoS ONE, 8 (1): e53347. [PMID:23335960]

15. Parker R, Liu M, Eyre HJ, Copeland NG, Gilbert DJ, Crawford J, Sutherland GR, Jenkins NA, Herzog H. (2000) Y-receptor-like genes GPR72 and GPR73: molecular cloning, genomic organisation and assignment to human chromosome 11q21.1 and 2p14 and mouse chromosome 9 and 6. Biochim Biophys Acta, 1491 (1-3): 369-75. [PMID:10760605]

16. Pesini P, Detheux M, Parmentier M, Hökfelt T. (1998) Distribution of a glucocorticoid-induced orphan receptor (JP05) mRNA in the central nervous system of the mouse. Brain Res Mol Brain Res, 57 (2): 281-300. [PMID:9675427]

17. Sah R, Parker SL, Sheriff S, Eaton K, Balasubramaniam A, Sallee FR. (2007) Interaction of NPY compounds with the rat glucocorticoid-induced receptor (GIR) reveals similarity to the NPY-Y2 receptor. Peptides, 28 (2): 302-9. [PMID:17240481]

18. Sah R, Pritchard LM, Richtand NM, Ahlbrand R, Eaton K, Sallee FR, Herman JP. (2005) Expression of the glucocorticoid-induced receptor mRNA in rat brain. Neuroscience, 133 (1): 281-92. [PMID:15893650]

19. Sugimoto N, Oida T, Hirota K, Nakamura K, Nomura T, Uchiyama T, Sakaguchi S. (2006) Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis. Int Immunol, 18 (8): 1197-209. [PMID:16772372]

20. Toms C, Jessup H, Thompson C, Baban D, Davies K, Powrie F. (2008) Gpr83 expression is not required for the maintenance of intestinal immune homeostasis and regulation of T-cell-dependent colitis. Immunology, 125 (3): 302-12. [PMID:18479351]

21. Wang D, Herman JP, Pritchard LM, Spitzer RH, Ahlbrand RL, Kramer GL, Petty F, Sallee FR, Richtand NM. (2001) Cloning, expression, and regulation of a glucocorticoid-induced receptor in rat brain: effect of repetitive amphetamine. J Neurosci, 21 (22): 9027-35. [PMID:11698613]

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