GPR139

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

   GtoImmuPdb view: OFF :     Currently no data for GPR139 in GtoImmuPdb

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
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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
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 Affinity Units Reference
NCRW0005-F05 Hs Antagonist 6.7 pIC50 8
pIC50 6.7 (IC50 2.1x10-7 M) [8]
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

Show »

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]

There should be a chart of expression data here, you may need to enable JavaScript!

References

Show »

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. Acta1722 (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 Screen14 (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 Model54 (6): 1553-7. [PMID:24826842]

4. Liu C, Bonaventure P, Lee G, Nepomuceno D, Kuei C, Wu J, Li Q, Joseph V, Sutton S, 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.,  [Epub ahead of print]. [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 Lett2 (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. Neuropharmacology50 (4): 512-20. [PMID:16378626]

8. 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

Show »

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: GPR139. Last modified on 16/09/2015. Accessed on 22/11/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=130.