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Gene and Protein Information ![]() |
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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 | 1,5,9 |
Mouse | 7 | 345 | 7 F2 | Gpr139 | G protein-coupled receptor 139 | 5,9 |
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 ![]() |
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Specialist databases | |
GPCRdb | gp139_human (Hs), gp139_mouse (Mm), gp139_rat (Rn) |
Other databases | |
Alphafold | Q6DWJ6 (Hs), Q80UC8 (Mm), P0C0W8 (Rn) |
ChEMBL Target | CHEMBL3632455 (Hs), CHEMBL4888453 (Rn) |
Ensembl Gene | ENSG00000180269 (Hs), ENSMUSG00000066197 (Mm), ENSRNOG00000023863 (Rn) |
Entrez Gene | 124274 (Hs), 209776 (Mm), 293545 (Rn) |
Human Protein Atlas | ENSG00000180269 (Hs) |
KEGG Gene | hsa:124274 (Hs), mmu:209776 (Mm), rno:293545 (Rn) |
Pharos | Q6DWJ6 (Hs) |
RefSeq Nucleotide | NM_001002911 (Hs), NM_001024138 (Mm), NM_00102424 (Rn) |
RefSeq Protein | NP_001002911 (Hs), NP_001019309 (Mm), NP_001019412 (Rn) |
UniProtKB | Q6DWJ6 (Hs), Q80UC8 (Mm), P0C0W8 (Rn) |
Wikipedia | GPR139 (Hs) |
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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Antagonists | ||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | ||||||||||||||||||||||||||||||||||||
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Primary Transduction Mechanisms ![]() |
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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 [9]. 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 ![]() |
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Expression Datasets ![]() |
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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 [10]. |
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. Pallareti L, Rath TF, Trapkov B, Tsonkov T, Nielsen AT, Harpsøe K, Gentry PR, Bräuner-Osborne H, Gloriam DE, Foster SR. (2023) Pharmacological characterization of novel small molecule agonists and antagonists for the orphan receptor GPR139. Eur J Pharmacol, 943: 175553. [PMID:36736525]
7. Reichard HA, Schiffer HH, Monenschein H, Atienza JM, Corbett G, Skaggs AW, Collia DR, Ray WJ, Serrats J, Bliesath J et al.. (2021) Discovery of TAK-041: a Potent and Selective GPR139 Agonist Explored for the Treatment of Negative Symptoms Associated with Schizophrenia. J Med Chem, 64 (15): 11527-11542. [PMID:34260228]
8. 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]
9. 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]
10. 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]
11. 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]
Alexander SP, Battey J, Benson HE, Benya RV, Bonner TI, Davenport AP, Dhanachandra Singh K, Eguchi S, Harmar A, Holliday N, Irving AJ, Jensen RT, Karnik S, Kostenis E, Liew WC, Monaghan AE, Mpamhanga C, Neubig R, Pawson AJ, Pin JP, Sharman JL, Spedding M, Spindel E, Stoddart L, Storjohann L, Thomas WG, Tirupula K, Vanderheyden P. Class A Orphans in GtoPdb v.2025.2. IUPHAR/BPS Guide to Pharmacology CITE. 2025; 2025(2). Available from: https://doi.org/10.2218/gtopdb/F16/2025.2.