ESRRG
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesESRRG, ERR3, ERRgamma, NR3B3, estrogen related receptor gamma, ERRg, ERR-gamma
External IDsOMIM: 602969 MGI: 1347056 HomoloGene: 55581 GeneCards: ESRRG
Orthologs
SpeciesHumanMouse
Entrez

2104

26381

Ensembl

ENSG00000196482

ENSMUSG00000026610

UniProt

P62508

P62509

RefSeq (mRNA)

NM_001243792
NM_011935
NM_001357534
NM_001357535
NM_001357536

RefSeq (protein)

NP_001230721
NP_036065
NP_001344463
NP_001344464
NP_001344465

Location (UCSC)Chr 1: 216.5 – 217.14 MbChr 1: 187.34 – 187.95 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

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).

Bisphenol A binding

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]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000196482 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026610 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "Entrez Gene: ESRRG estrogen-related receptor gamma".
  6. ↑ Eudy JD, Yao S, Weston MD, Ma-Edmonds M, Talmadge CB, Cheng JJ, Kimberling WJ, Sumegi J (Jun 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.
  7. ↑ Chen F, Zhang Q, McDonald T, Davidoff MJ, Bailey W, Bai C, Liu Q, Caskey CT (Mar 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.
  8. 1 2 3 4 5 Matsushima A, Kakuta Y, Teramoto T, Koshiba T, Liu X, Okada H, Tokunaga T, Kawabata S, Kimura M, Shimohigashi Y (Oct 2007). "Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERR gamma". Journal of Biochemistry. 142 (4): 517–24. doi:10.1093/jb/mvm158. PMID 17761695.
  9. ↑ Huppunen J, Aarnisalo P (Feb 2004). "Dimerization modulates the activity of the orphan nuclear receptor ERRgamma". Biochemical and Biophysical Research Communications. 314 (4): 964–70. doi:10.1016/j.bbrc.2003.12.194. PMID 14751226.
  10. ↑ Babu S, Vellore NA, Kasibotla AV, Dwayne HJ, Stubblefield MA, Uppu RM (Sep 2012). "Molecular docking of bisphenol A and its nitrated and chlorinated metabolites onto human estrogen-related receptor-gamma". Biochemical and Biophysical Research Communications. 426 (2): 215–20. doi:10.1016/j.bbrc.2012.08.065. PMID 22935422.
  11. ↑ Takeda Y, Liu X, Sumiyoshi M, Matsushima A, Shimohigashi M, Shimohigashi Y (Jul 2009). "Placenta expressing the greatest quantity of bisphenol A receptor ERR{gamma} among the human reproductive tissues: Predominant expression of type-1 ERRgamma isoform". Journal of Biochemistry. 146 (1): 113–22. doi:10.1093/jb/mvp049. PMID 19304792.

Further reading

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