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G protein-coupled receptor 176 (GPR176)
- Target
- GPR176
- Molecular classification
- G protein-coupled receptor, Orphan receptor, Class A (rhodopsin-like) GPCR
01
Overview
G protein-coupled receptor 176 (GPR176) is an orphan class A GPCR highly expressed in the suprachiasmatic nucleus of the hypothalamus, where it sets the pace of circadian behavior by negatively regulating cAMP production through coupling with the unique Gz subclass of heterotrimeric G proteins. Unlike many GPCRs, GPR176 exhibits constitutive (agonist-independent) repression of adenylyl cyclase. It is glycosylated at several N-terminal sites, a post-translational modification essential for its expression and function. Beyond its role in circadian regulation, altered GPR176 expression is implicated in several cancers, including breast cancer, influencing tumor cell proliferation, migration, and prognosis, making it a potential biomarker and therapeutic target in oncology and chronotherapy[1][2][3][4].
- Other names
- GPR176Gm1012HB-954probable G-protein coupled receptor 176Gpr176
02
Mechanism of action
For potential drugs: Negative regulation of cAMP via Gz-protein coupling. Agonist-independent (constitutive) inhibition of adenylyl cyclase activity.
03
Biological functions
Regulation of circadian rhythmSignal transductioncAMP repressionBrain function modulationCell proliferation and migration (cancer context)
04
Disease associations
Cancer (including breast cancer and mesothelioma)Circadian rhythm disorders
05
Safety considerations
No specific drug safety concerns reported, but possible impact on circadian rhythm and brain functionPotential off-target risks due to brain expression and role in clock regulation
06
Biomarkers
GPR176 expression level (tumor aggressiveness/prognosis in breast cancer)GPR176 promoter methylation status (correlates with mRNA levels in cancer)N-glycosylation site variants (protein stability and signaling function)
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