Estrogen-related receptor gamma

Estrogen-related receptor gamma
Estrogen-related receptor gamma

PDB rendering based on 1kv6.
Symbols ESRRG; DKFZp781L1617; ERR3; ERRgamma; FLJ16023; KIAA0832; NR3B3
External IDs OMIM602969 MGI1347056 HomoloGene55581 IUPHAR: NR3B3 GeneCards: ESRRG Gene
RNA expression pattern
PBB GE ESRRG 207981 s at tn.png
PBB GE ESRRG 209966 x at tn.png
More reference expression data
Species Human Mouse
Entrez 2104 26381
Ensembl ENSG00000196482 ENSMUSG00000026610
UniProt P62508 Q3US92
RefSeq (mRNA) NM_001134285.1 NM_011935.2
RefSeq (protein) NP_001127757.1 NP_036065.1
Location (UCSC) Chr 1:
216.68 – 217.31 Mb
Chr 1:
189.43 – 190.04 Mb
PubMed search [1] [2]

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.[1][2][3] It behaves as a constitutive activator of transcription.[4]

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.[5] It also seems to be the target of bisphenol A (see below).

Bisphenol A binding

There is evidence that bisphenol A functions as an endocrine disruptor by binding strongly to ERR-γ.[4] BPA seems to binds strongly to ERR-γ (dissociation constant = 5.5 nM), but not to the estrogen receptor (ER).[4] BPA binding to ERR-γ preserves its basal constitutive activity.[4] It can also protect it from deactivation from the selective estrogen receptor modulator 4-hydroxytamoxifen.[4]

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.[6]


  1. ^ "Entrez Gene: ESRRG estrogen-related receptor gamma". 
  2. ^ Eudy JD, Yao S, Weston MD, Ma-Edmonds M, Talmadge CB, Cheng JJ, Kimberling WJ, Sumegi J (June 1998). "Isolation of a gene encoding a novel member of the nuclear receptor superfamily from the critical region of Usher syndrome type IIa at 1q41". Genomics 50 (3): 382–4. doi:10.1006/geno.1998.5345. PMID 9676434. 
  3. ^ Chen F, Zhang Q, McDonald T, Davidoff MJ, Bailey W, Bai C, Liu Q, Caskey CT (March 1999). "Identification of two hERR2-related novel nuclear receptors utilizing bioinformatics and inverse PCR". Gene 228 (1–2): 101–9. doi:10.1016/S0378-1119(98)00619-2. PMID 10072763. 
  4. ^ a b c d e Matsushima A, Kakuta Y, Teramoto T, Koshiba T, Liu X, Okada H, Tokunaga T, Kawabata S, Kimura M, Shimohigashi Y (October 2007). "Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERR gamma". J. Biochem. 142 (4): 517–24. doi:10.1093/jb/mvm158. PMID 17761695. 
  5. ^ Huppunen J, Aarnisalo P (February 2004). "Dimerization modulates the activity of the orphan nuclear receptor ERRgamma". Biochem. Biophys. Res. Commun. 314 (4): 964–70. doi:10.1016/j.bbrc.2003.12.194. PMID 14751226. 
  6. ^ Takeda Y, Liu X, Sumiyoshi M, Matsushima A, Shimohigashi M, Shimohigashi Y (July 2009). "Placenta expressing the greatest quantity of bisphenol A receptor ER-γ among the human reproductive tissues: Predominant expression of type-1 ERRgamma isoform". J. Biochem. 146 (1): 113–22. doi:10.1093/jb/mvp049. PMID 19304792. 

Further reading

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