Estrogen-related receptor gamma
{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
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.{{cite web | title = Entrez Gene: ESRRG estrogen-related receptor gamma| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2104}}{{cite journal | vauthors = Eudy JD, Yao S, Weston MD, Ma-Edmonds M, Talmadge CB, Cheng JJ, Kimberling WJ, Sumegi J | title = Isolation of a gene encoding a novel member of the nuclear receptor superfamily from the critical region of Usher syndrome type IIa at 1q41 | journal = Genomics | volume = 50 | issue = 3 | pages = 382–4 | date = Jun 1998 | pmid = 9676434 | doi = 10.1006/geno.1998.5345 }}{{cite journal | vauthors = Chen F, Zhang Q, McDonald T, Davidoff MJ, Bailey W, Bai C, Liu Q, Caskey CT | title = Identification of two hERR2-related novel nuclear receptors utilizing bioinformatics and inverse PCR | journal = Gene | volume = 228 | issue = 1–2 | pages = 101–9 | date = Mar 1999 | pmid = 10072763 | doi = 10.1016/S0378-1119(98)00619-2 }} It behaves as a constitutive activator of transcription.
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.{{cite journal | vauthors = Huppunen J, Aarnisalo P | title = Dimerization modulates the activity of the orphan nuclear receptor ERRgamma | journal = Biochemical and Biophysical Research Communications | volume = 314 | issue = 4 | pages = 964–70 | date = Feb 2004 | pmid = 14751226 | doi = 10.1016/j.bbrc.2003.12.194 }} It also seems to be the target of bisphenol A (see below).
Bisphenol A binding
{{Further|Bisphenol A}}
There is evidence that bisphenol A functions as a xenoestrogen by binding strongly to ERR-γ. 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).,{{cite journal | vauthors = Babu S, Vellore NA, Kasibotla AV, Dwayne HJ, Stubblefield MA, Uppu RM | title = Molecular docking of bisphenol A and its nitrated and chlorinated metabolites onto human estrogen-related receptor-gamma | journal = Biochemical and Biophysical Research Communications | volume = 426 | issue = 2 | pages = 215–20 | date = Sep 2012 | pmid = 22935422 | doi = 10.1016/j.bbrc.2012.08.065 }} BPA binding to ERR-γ preserves its basal constitutive activity. It can also protect it from deactivation from the selective estrogen receptor modulator 4-hydroxytamoxifen.{{cite journal | vauthors = Matsushima A, Kakuta Y, Teramoto T, Koshiba T, Liu X, Okada H, Tokunaga T, Kawabata S, Kimura M, Shimohigashi Y | title = Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERR gamma | journal = Journal of Biochemistry | volume = 142 | issue = 4 | pages = 517–24 | date = Oct 2007 | pmid = 17761695 | doi = 10.1093/jb/mvm158 }}
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.{{cite journal | vauthors = Takeda Y, Liu X, Sumiyoshi M, Matsushima A, Shimohigashi M, Shimohigashi Y | title = Placenta expressing the greatest quantity of bisphenol A receptor ERR{gamma} among the human reproductive tissues: Predominant expression of type-1 ERRgamma isoform | journal = Journal of Biochemistry | volume = 146 | issue = 1 | pages = 113–22 | date = Jul 2009 | pmid = 19304792 | doi = 10.1093/jb/mvp049 }}
References
{{Reflist}}
Further reading
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- {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = Sep 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 | doi-access = free }}
- {{cite journal | vauthors = Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro | journal = DNA Research | volume = 5 | issue = 6 | pages = 355–64 | date = Dec 1998 | pmid = 10048485 | doi = 10.1093/dnares/5.6.355 | doi-access = free }}
- {{cite journal | vauthors = Hong H, Yang L, Stallcup MR | title = Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERR3 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 32 | pages = 22618–26 | date = Aug 1999 | pmid = 10428842 | doi = 10.1074/jbc.274.32.22618 | doi-access = free }}
- {{cite journal | vauthors = Heard DJ, Norby PL, Holloway J, Vissing H | title = Human ERRgamma, a third member of the estrogen receptor-related receptor (ERR) subfamily of orphan nuclear receptors: tissue-specific isoforms are expressed during development and in the adult | journal = Molecular Endocrinology | volume = 14 | issue = 3 | pages = 382–92 | date = Mar 2000 | doi = 10.1210/mend.14.3.0431 | pmid = 10707956 | doi-access = free }}
- {{cite journal | vauthors = Greschik H, Wurtz JM, Sanglier S, Bourguet W, van Dorsselaer A, Moras D, Renaud JP | title = Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3 | journal = Molecular Cell | volume = 9 | issue = 2 | pages = 303–13 | date = Feb 2002 | pmid = 11864604 | doi = 10.1016/S1097-2765(02)00444-6 | doi-access = free }}
- {{cite journal | vauthors = Wistow G, Bernstein SL, Wyatt MK, Fariss RN, Behal A, Touchman JW, Bouffard G, Smith D, Peterson K | title = Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: over 6000 non-redundant transcripts, novel genes and splice variants | journal = Molecular Vision | volume = 8 | pages = 205–20 | date = Jun 2002 | pmid = 12107410 }}
- {{cite journal | vauthors = Hentschke M, Süsens U, Borgmeyer U | title = Domains of ERRgamma that mediate homodimerization and interaction with factors stimulating DNA binding | journal = European Journal of Biochemistry | volume = 269 | issue = 16 | pages = 4086–97 | date = Aug 2002 | pmid = 12180985 | doi = 10.1046/j.1432-1033.2002.03102.x }}
- {{cite journal | vauthors = Hentschke M, Süsens U, Borgmeyer U | title = PGC-1 and PERC, coactivators of the estrogen receptor-related receptor gamma | journal = Biochemical and Biophysical Research Communications | volume = 299 | issue = 5 | pages = 872–9 | date = Dec 2002 | pmid = 12470660 | doi = 10.1016/S0006-291X(02)02753-5 }}
- {{cite journal | vauthors = Hentschke M, Schulze C, Süsens U, Borgmeyer U | title = Characterization of calmodulin binding to the orphan nuclear receptor Errgamma | journal = Biological Chemistry | volume = 384 | issue = 3 | pages = 473–82 | date = Mar 2003 | pmid = 12715898 | doi = 10.1515/BC.2003.053 | s2cid = 41163978 }}
- {{cite journal | vauthors = Hentschke M, Borgmeyer U | title = Identification of PNRC2 and TLE1 as activation function-1 cofactors of the orphan nuclear receptor ERRgamma | journal = Biochemical and Biophysical Research Communications | volume = 312 | issue = 4 | pages = 975–82 | date = Dec 2003 | pmid = 14651967 | doi = 10.1016/j.bbrc.2003.11.025 }}
- {{cite journal | vauthors = Cheung CP, Yu S, Wong KB, Chan LW, Lai FM, Wang X, Suetsugi M, Chen S, Chan FL | title = Expression and functional study of estrogen receptor-related receptors in human prostatic cells and tissues | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 90 | issue = 3 | pages = 1830–44 | date = Mar 2005 | pmid = 15598686 | doi = 10.1210/jc.2004-1421 | doi-access = free }}
- {{cite journal | vauthors = Liu D, Zhang Z, Teng CT | title = Estrogen-related receptor-gamma and peroxisome proliferator-activated receptor-gamma coactivator-1alpha regulate estrogen-related receptor-alpha gene expression via a conserved multi-hormone response element | journal = Journal of Molecular Endocrinology | volume = 34 | issue = 2 | pages = 473–87 | date = Apr 2005 | pmid = 15821111 | doi = 10.1677/jme.1.01586 | doi-access = free }}
- {{cite journal | vauthors = Gao M, Sun P, Wang J, Zhao D, Wei L | title = Expression of estrogen receptor-related receptor isoforms and clinical significance in endometrial adenocarcinoma | journal = International Journal of Gynecological Cancer | volume = 16 | issue = 2 | pages = 827–33 | year = 2006 | pmid = 16681769 | doi = 10.1111/j.1525-1438.2006.00527.x | s2cid = 37213476 }}
- {{cite journal | vauthors = Wang L, Zuercher WJ, Consler TG, Lambert MH, Miller AB, Orband-Miller LA, McKee DD, Willson TM, Nolte RT | title = X-ray crystal structures of the estrogen-related receptor-gamma ligand binding domain in three functional states reveal the molecular basis of small molecule regulation | journal = The Journal of Biological Chemistry | volume = 281 | issue = 49 | pages = 37773–81 | date = Dec 2006 | pmid = 16990259 | doi = 10.1074/jbc.M608410200 | doi-access = free }}
- {{cite journal | vauthors = Babu S, Vellore NA, Kasibotla AV, Dwayne HJ, Stubblefield MA, Uppu RM | title = Molecular docking of bisphenol A and its nitrated and chlorinated metabolites onto human estrogen-related receptor-gamma | journal = Biochemical and Biophysical Research Communications | volume = 426 | issue = 2 | pages = 215–20 | date = Sep 2012 | pmid = 22935422 | doi = 10.1016/j.bbrc.2012.08.065 }}
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{{PDB Gallery|geneid=2104}}
{{Transcription factors|g2}}
{{Estrogen-related receptor modulators}}
Category:Intracellular receptors