Estrogen-related receptor gamma (ERR-gamma), also known as NR3B3 (nuclear receptor subfamily 3, group B, member 3), is a nuclear receptor that in humans is encoded by the ESRRG (EStrogen Related Receptor Gamma) gene.[5][6][7] It behaves as a constitutive activator of transcription.[8]
ESRRG | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | ESRRG, ERR3, ERRgamma, NR3B3, estrogen related receptor gamma, ERRg, ERR-gamma | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 602969 MGI: 1347056 HomoloGene: 55581 GeneCards: ESRRG | ||||||||||||||||||||||||||||||||||||||||||||||||||
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This protein is a member of nuclear hormone receptor family of steroid hormone receptors. No physiological activating ligand is known for this orphan receptor, but 4-hydroxytamoxifen and diethylstilbestrol act as inverse agonists and deactivate ESRRG.[9] It also seems to be the target of bisphenol A (see below).
There is evidence that bisphenol A functions as a xenoestrogen by binding strongly to ERR-γ.[8] BPA as well as its nitrated and chlorinated metabolites seems to binds strongly to ERR-γ (dissociation constant = 5.5 nM), but not to the estrogen receptor (ER).,[8][10] BPA binding to ERR-γ preserves its basal constitutive activity.[8] It can also protect it from deactivation from the selective estrogen receptor modulator 4-hydroxytamoxifen.[8]
Different expression of ERR-γ in different parts of the body may account for variations in bisphenol A effects. For instance, ERR-γ has been found in high concentration in the placenta, explaining reports of high bisphenol A accumulation there.[11]