<i>GPR139</i> | Class A Orphans | IUPHAR/BPS Guide to PHARMACOLOGY

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GPR139

Target not currently curated in GtoImmuPdb

Target id: 130

Nomenclature: GPR139

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

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 353 16p12.3 GPR139 G protein-coupled receptor 139 1,5,7
Mouse 7 345 7 F1 Gpr139 G protein-coupled receptor 139 5,7
Rat 7 345 1q35 Gpr139 G protein-coupled receptor 139 1,5
Previous and Unofficial Names
G(q)-coupled orphan receptor GPRg1 | GPRG1 | G-protein-coupled receptor PGR3
Database Links
Specialist databases
GPCRDB gp139_human (Hs), gp139_mouse (Mm), gp139_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
L-phenylalanine
L-tryptophan

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 Value Parameter Reference
JNJ-63533054 Hs Agonist 7.6 pKi 4
pKi 7.6 (Ki 2.4x10-8 M) [4]
L-tryptophan Hs Agonist 3.1 pKi 4
pKi 3.1 (Ki 7.38x10-4 M) [4]
Description: Inhibition equilibrium constant from a radioligand membrane binding assay.
L-phenylalanine Hs Agonist 3.1 pKi 4
pKi 3.1 (Ki 8.72x10-4 M) [4]
Description: Inhibition equilibrium constant from a radioligand membrane binding assay.
compound 1a [PMID: 24900311] Hs Full agonist 7.4 pEC50 6
pEC50 7.4 (EC50 3.9x10-8 M) [6]
L-tryptophan Hs Agonist 3.7 pEC50 3
pEC50 3.7 (EC50 2.2x10-4 M) [3]
L-phenylalanine Hs Agonist 3.5 pEC50 3
pEC50 3.5 (EC50 3.2x10-4 M) [3]
L-tryptophan Hs Agonist 4.6 pIC50 4
pIC50 4.6 (IC50 2.6x10-5 M) [4]
Description: Measured using a GTPγS assay in transfected COS7 cells.
L-phenylalanine Hs Agonist 4.5 pIC50 4
pIC50 4.5 (IC50 3.1x10-5 M) [4]
Description: Measured using a GTPγS assay in transfected COS7 cells.
LP-360924 Hs Agonist - - 2
[2]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
NCRW0005-F05 Hs Antagonist 6.7 pIC50 9
pIC50 6.7 (IC50 2.1x10-7 M) [9]
LP-471756 Hs Antagonist 6.2 pIC50 2
pIC50 6.2 (IC50 6.4x10-7 M) [2]
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Other - See Comments
Comments:  GPR139 is coupled with Gq/11 protein which leads to activation of serum response element (SRE) and cAMP response element (CRE) [5]. However, Susens et al. show that GPR139 signaling does not require Gi and Gq coupling [7]. Instead, it is mediated by an inhibitory G-protein and phospholipase C. Dimer formation may be required for proper signaling function.
References:  5
Tissue Distribution
Central nervous system, mainly in the caudate putamen and hypothalamus
Species:  Human
Technique:  RT-PCR
References:  5
Various brain regions. High expression in putamen, medulla and caudate nucleus. Low expression in thalamus, amygdala and spinal cord.
Species:  Human
Technique:  Northern blot
References:  7
High expression in ventrolateral region of caudate putamen, habenular nucleus, zona incerta and medial mammillary nucleus.
Species:  Mouse
Technique:  in situ hybridisation
References:  5
Median habenular nucleus
Species:  Mouse
Technique:  in situ hybridisation
References:  7
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 Comments
A forward genetic screen in a behavioural model using C. elegans suggests that GPR139 negatively regulates μ opioid receptor signalling [8].

References

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1. Gloriam DE, Schiöth HB, Fredriksson R. (2005) Nine new human Rhodopsin family G-protein coupled receptors: identification, sequence characterisation and evolutionary relationship. Biochim. Biophys. Acta, 1722 (3): 235-46. [PMID:15777626]

2. Hu LA, Tang PM, Eslahi NK, Zhou T, Barbosa J, Liu Q. (2009) Identification of surrogate agonists and antagonists for orphan G-protein-coupled receptor GPR139. J Biomol Screen, 14 (7): 789-97. [PMID:19525486]

3. Isberg V, Andersen KB, Bisig C, Dietz GP, Bräuner-Osborne H, Gloriam DE. (2014) Computer-aided discovery of aromatic l-α-amino acids as agonists of the orphan G protein-coupled receptor GPR139. J Chem Inf Model, 54 (6): 1553-7. [PMID:24826842]

4. Liu C, Bonaventure P, Lee G, Nepomuceno D, Kuei C, Wu J, Li Q, Joseph V, Sutton SW, Eckert W et al.. (2015) GPR139, an Orphan Receptor Highly Enriched in the Habenula and Septum, Is Activated by the Essential Amino Acids L-Tryptophan and L-Phenylalanine. Mol. Pharmacol., 88 (5): 911-25. [PMID:26349500]

5. Matsuo A, Matsumoto S, Nagano M, Masumoto KH, Takasaki J, Matsumoto M, Kobori M, Katoh M, Shigeyoshi Y. (2005) Molecular cloning and characterization of a novel Gq-coupled orphan receptor GPRg1 exclusively expressed in the central nervous system. Biochem. Biophys. Res. Commun., 331 (1): 363-9. [PMID:15845401]

6. Shi F, Shen JK, Chen D, Fog K, Thirstrup K, Hentzer M, Karlsson JJ, Menon V, Jones KA, Smith KE et al.. (2011) Discovery and SAR of a Series of Agonists at Orphan G Protein-Coupled Receptor 139. ACS Med Chem Lett, 2 (4): 303-6. [PMID:24900311]

7. Süsens U, Hermans-Borgmeyer I, Urny J, Schaller HC. (2006) Characterisation and differential expression of two very closely related G-protein-coupled receptors, GPR139 and GPR142, in mouse tissue and during mouse development. Neuropharmacology, 50 (4): 512-20. [PMID:16378626]

8. Wang D, Stoveken HM, Zucca S, Dao M, Orlandi C, Song C, Masuho I, Johnston C, Opperman KJ, Giles AC et al.. (2019) Genetic behavioral screen identifies an orphan anti-opioid system. Science, 365 (6459): 1267-1273. [PMID:31416932]

9. Wang J, Zhu LY, Liu Q, Hentzer M, Smith GP, Wang MW. (2015) High-throughput screening of antagonists for the orphan G-protein coupled receptor GPR139. Acta Pharmacol. Sin., 36 (7): 874-8. [PMID:26027661]

Contributors

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