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GPR61

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Target not currently curated in GtoImmuPdb

Target id: 110

Nomenclature: GPR61

Family: Class A Orphans

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 7 451 1p13.3 GPR61 G protein-coupled receptor 61 1
Mouse 7 449 3 F2.3 Gpr61 G protein-coupled receptor 61
Rat 7 449 2q34 Gpr61 G protein-coupled receptor 61
Previous and Unofficial Names Click here for help
GPCR3 | BALGR | biogenic amine receptor-like GPCR
Database Links Click here for help
Specialist databases
GPCRdb gpr61_human (Hs), gpr61_mouse (Mm)
Other databases
Alphafold Q9BZJ8 (Hs), Q8C010 (Mm)
ChEMBL Target CHEMBL4523918 (Hs)
Ensembl Gene ENSG00000156097 (Hs), ENSMUSG00000046793 (Mm), ENSRNOG00000019738 (Rn)
Entrez Gene 83873 (Hs), 229714 (Mm), 310780 (Rn)
Human Protein Atlas ENSG00000156097 (Hs)
KEGG Gene hsa:83873 (Hs), mmu:229714 (Mm), rno:310780 (Rn)
OMIM 606916 (Hs)
Pharos Q9BZJ8 (Hs)
RefSeq Nucleotide NM_031936 (Hs), NM_175470 (Mm), NM_001107715 (Rn)
RefSeq Protein NP_114142 (Hs), NP_780679 (Mm), NP_001101185 (Rn)
UniProtKB Q9BZJ8 (Hs), Q8C010 (Mm)
Wikipedia GPR61 (Hs)

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 1 [PMID: 37741852] Small molecule or natural product Ligand has a PDB structure Hs Inverse agonist 8.0 pIC50 2
⤷ pIC50 8.0 (IC50 1x10-8 M) [2]
Description: Determined using a cAMP assay in cells overexpressing hGPR61
Antagonist Comments
Although no endogenous ligands have been identified, 5-(nonyloxy)tryptamine has been reported to be a low affinity inverse agonist [4].
Primary Transduction Mechanisms Click here for help
Comments:  Possibly Gs-coupled. The receptor displays constitutive activity that is abolished by deletion of the N-terminal 25 amino acids [5].
References:  5
Tissue Distribution Click here for help
Brain, testes
Species:  Human
Technique:  Semi-quantitative PCR
References:  1
Cerebral cortex, occipital pole, frontal lobe, temporal lobe, amygdala, hippocampus (lower expression in putamen and caudate nucleus)
Species:  Human
Technique:  Northern blot
References:  1
Dentate gyrus, hippocampus, cerebral cortex (moderate to weak expression in hypothalamus, central amygdala, nucleus accumbens and nucleus tractus solitarius)
Species:  Mouse
Technique:  RT-PCR
References:  3
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 Consequences of Altering Gene Expression Click here for help
GPR61 deficient mice exhibit obesity associated with hyperphagia. Significantly lower mRNA levels of pro-opiomelanocortin and brain-derived neurotropic factor mRNAs in hypothalamus compared to wild type. Phenotype displayed: hyperphagia, increased visceral fat pad weight, increased liver weight and triglyceride content, increased plasma leptin and insulin levels.
Species:  Mouse
Tissue:  Live, adipose, plasma
Technique:  Targeted gene disruption
References:  3
Gene Expression and Pathophysiology Comments
Mouse models of GPR61 disruption indicate a role for the receptor in regulation of appetite and body weight, indicating that the receptor may be a therapeutic target for obesity and eating disorders.
Biologically Significant Variants Click here for help
Type:  Naturally occurring SNP
Species:  Human
Amino acid change:  L218P
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession:  rs75311269
General Comments
Site-directed mutagenesis studies suggest a possible role for the N-terminal 25 amino acids of the receptor in constitutive activity and for membrane translocation of the receptor [5].

References

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1. Cikos S, Gregor P, Koppel J. (2001) Cloning of a novel biogenic amine receptor-like G protein-coupled receptor expressed in human brain. Biochim Biophys Acta, 1521 (1-3): 66-72. [PMID:11690637]

2. Lees JA, Dias JM, Rajamohan F, Fortin JP, O'Connor R, Kong JX, Hughes EAG, Fisher EL, Tuttle JB, Lovett G et al.. (2023) An inverse agonist of orphan receptor GPR61 acts by a G protein-competitive allosteric mechanism. Nat Commun, 14 (1): 5938. [PMID:37741852]

3. Nambu H, Fukushima M, Hikichi H, Inoue T, Nagano N, Tahara Y, Nambu T, Ito J, Ogawa Y, Ozaki S et al.. (2011) Characterization of metabolic phenotypes of mice lacking GPR61, an orphan G-protein coupled receptor. Life Sci, 89 (21-22): 765-72. [PMID:21971119]

4. Takeda S, Okada T, Okamura M, Haga T, Isoyama-Tanaka J, Kuwahara H, Minamino N. (2004) The receptor-Galpha fusion protein as a tool for ligand screening: a model study using a nociceptin receptor-Galphai2 fusion protein. J Biochem, 135 (5): 597-604. [PMID:15173198]

5. Toyooka M, Tujii T, Takeda S. (2009) The N-terminal domain of GPR61, an orphan G-protein-coupled receptor, is essential for its constitutive activity. J Neurosci Res, 87 (6): 1329-33. [PMID:19025769]

Contributors

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