Estrogen-related receptor

Function

Estrogen-related receptor (ERR) binds to estrogen response elements on DNA and modulates transcription in response to hormone. It is a nuclear receptor. There are 3 classes of ERR : ERRα, ERRβ and ERRγ.

ERR alpha regulates cellular metabolism and function^[1].
ERR betais expressed in the inner ear and controls the development of its endolymph-producing cells^[2].

Relevance

ERR plays a role in energy homeostasis and cancer^[3]. ERRα and ERRγ are overexpressed in breast cancer and can serve as prognostic markers or therapeutic targets.

Structural insights

to human estrogen-related receptor γ. The chemotherapeutic drugs bisphenol and are nestled between 4 alpha helices in the ERR active site ^[4].

3D structures of estrogen-related receptor

Estrogen-related receptor 3D structures

Human estrogen-related receptor γ ligand-binding domain (cyan, grey, green, yellow, pink, purple) complex with nuclear receptor corepressor 2 peptide (dark red, orange) and 4-hydroxytamoxifen (PDB code 2gpv)

Drag the structure with the mouse to rotate

ReferencesReferences

↑ Tripathi M, Yen PM, Singh BK. Estrogen-Related Receptor Alpha: An Under-Appreciated Potential Target for the Treatment of Metabolic Diseases. Int J Mol Sci. 2020 Feb 28;21(5):1645. PMID:32121253 doi:10.3390/ijms21051645
↑ Chen J, Nathans J. Estrogen-related receptor beta/NR3B2 controls epithelial cell fate and endolymph production by the stria vascularis. Dev Cell. 2007 Sep;13(3):325-37. PMID:17765677 doi:10.1016/j.devcel.2007.07.011
↑ Ariazi EA, Jordan VC. Estrogen-related receptors as emerging targets in cancer and metabolic disorders. Curr Top Med Chem. 2006;6(3):203-15. PMID:16515477
↑ Wang L, Zuercher WJ, Consler TG, Lambert MH, Miller AB, Orband-Miller LA, McKee DD, Willson TM, Nolte RT. 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. J Biol Chem. 2006 Dec 8;281(49):37773-81. Epub 2006 Sep 21. PMID:16990259 doi:http://dx.doi.org/10.1074/jbc.M608410200

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Michal Harel, Wayne Decatur, Alexander Berchansky

[1] Tripathi M, Yen PM, Singh BK. Estrogen-Related Receptor Alpha: An Under-Appreciated Potential Target for the Treatment of Metabolic Diseases. Int J Mol Sci. 2020 Feb 28;21(5):1645. PMID:32121253 doi:10.3390/ijms21051645

[2] Chen J, Nathans J. Estrogen-related receptor beta/NR3B2 controls epithelial cell fate and endolymph production by the stria vascularis. Dev Cell. 2007 Sep;13(3):325-37. PMID:17765677 doi:10.1016/j.devcel.2007.07.011

[3] Ariazi EA, Jordan VC. Estrogen-related receptors as emerging targets in cancer and metabolic disorders. Curr Top Med Chem. 2006;6(3):203-15. PMID:16515477

[4] Wang L, Zuercher WJ, Consler TG, Lambert MH, Miller AB, Orband-Miller LA, McKee DD, Willson TM, Nolte RT. 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. J Biol Chem. 2006 Dec 8;281(49):37773-81. Epub 2006 Sep 21. PMID:16990259 doi:http://dx.doi.org/10.1074/jbc.M608410200

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