Biology:GPR139
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
G-protein coupled receptor 139 (GPC139) is a protein that in humans is encoded by the GPR139 gene.[1][2] Research has shown that mice with loss of GCP139 experience schizophrenia-like symptomatology that is rescued with the dopamine receptor antagonist haloperidol and the μ-opioid receptor antagonist naltrexone.[3][4]
GPR139 is activated by L-tryptophan and L-phenylalanine, though only at relatively high concentrations,[5] but in 2025, GPR139 was identified as a novel opioid receptor, specifically of dynorphins.[6]
Ligands
Agonists
- JNJ-63533054
- Zelatriazin (TAK-41), (NBI-1065846) a potent, and GPR139 receptor selective agonist [7] which was in clinical trials to gauge the efficacy for treating psychiatric conditions such as major depressive disorder and the negative symptoms of schizophrenia, but was later dropped from development.
- TC-O 9311 [444932-31-4]
Antagonists
References
- ↑ "The G protein-coupled receptor repertoires of human and mouse". Proceedings of the National Academy of Sciences of the United States of America 100 (8): 4903–4908. April 2003. doi:10.1073/pnas.0230374100. PMID 12679517. Bibcode: 2003PNAS..100.4903V.
- ↑ "Entrez Gene: GPR139 G protein-coupled receptor 139". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=124274.
- ↑ "The role of orphan receptor GPR139 in neuropsychiatric behavior". Neuropsychopharmacology 47 (4): 902–913. March 2022. doi:10.1038/s41386-021-00962-2. PMID 33479510.
- ↑ "Pharmacology and function of the orphan GPR139 G protein-coupled receptor". Basic & Clinical Pharmacology & Toxicology 126 (Suppl 6): 35–46. June 2020. doi:10.1111/bcpt.13263. PMID 31132229.
- ↑ "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. Nov 2015. doi:10.1124/mol.115.100412. PMID 26349500.
- ↑ "Homeostatic scaling of dynorphin signaling by a non-canonical opioid receptor". Nature Communications 16 (1): 6786. July 2025. doi:10.1038/s41467-025-62133-x. PMID 40701991.
- ↑ "Discovery of TAK-041: a Potent and Selective GPR139 Agonist Explored for the Treatment of Negative Symptoms Associated with Schizophrenia". Journal of Medicinal Chemistry 64 (15): 11527–11542. August 2021. doi:10.1021/acs.jmedchem.1c00820. PMID 34260228.
Further reading
- "Novel human G-protein-coupled receptors". Biochemical and Biophysical Research Communications 305 (1): 67–71. May 2003. doi:10.1016/S0006-291X(03)00709-5. PMID 12732197.
- "Novel paralogy relations among human chromosomes support a link between the phylogeny of doublesex-related genes and the evolution of sex determination". Genomics 79 (3): 333–343. March 2002. doi:10.1006/geno.2002.6711. PMID 11863363.
- "Identification of G protein-coupled receptor genes from the human genome sequence". FEBS Letters 520 (1–3): 97–101. June 2002. doi:10.1016/S0014-5793(02)02775-8. PMID 12044878.
- "Nine new human Rhodopsin family G-protein coupled receptors: identification, sequence characterisation and evolutionary relationship". Biochimica et Biophysica Acta (BBA) - General Subjects 1722 (3): 235–246. April 2005. doi:10.1016/j.bbagen.2004.12.001. PMID 15777626.
- "Molecular cloning and characterization of a novel Gq-coupled orphan receptor GPRg1 exclusively expressed in the central nervous system". Biochemical and Biophysical Research Communications 331 (1): 363–369. May 2005. doi:10.1016/j.bbrc.2005.03.174. PMID 15845401.
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