Biology:Estrogen-related receptor

From HandWiki
Short description: Orphan nuclear receptor
estrogen-related receptor alpha
Identifiers
SymbolESRRA
Alt. symbolsESRL1
NCBI gene2101
HGNC3471
OMIM601998
RefSeqNM_004451
UniProtP11474
Other data
LocusChr. 11 q12
estrogen-related receptor beta
Identifiers
SymbolESRRB
Alt. symbolsESRL2
NCBI gene2103
HGNC3473
OMIM602167
RefSeqNM_004452
UniProtO95718
Other data
LocusChr. 14 q24.3
estrogen-related receptor gamma
Identifiers
SymbolESRRG
NCBI gene2104
HGNC3474
OMIM602969
RefSeqNM_206595
UniProtP62508
Other data
LocusChr. 1 q41

The ERRs are orphan nuclear receptors, meaning the identity of their endogenous ligand has yet to be unambiguously determined. They are named because of sequence homology with estrogen receptors, but do not appear to bind estrogens or other tested steroid hormones.

There are three human estrogen related receptors:

ERRs bind enhancers throughout the genome where they exert effects on gene regulation. The ERR family exhibit varying transcriptional activation capabilities and physically interact with the transcriptional co-activators PGC1-alpha and PGC1-beta,[1][2][3][4][5] via their AF-2 domains and the leucine-rich nuclear receptor interacting motifs (LxxLL) present in the PGC-1 proteins,[6] The ERR family have been demonstrated to control energy homeostasis,[6][7] oxidative metabolism,[1][8] and mitochondrial biogenesis,[1] while effecting mammalian physiology in the heart,[9][10][11][12] brown adipose tissue,[13][14][15] white adipose tissue,[16] placenta,[17] macrophages,[2] and demonstrated additional roles in diabetes and cancer.[18] The contributions of individual ERRs to physiology continue to be elucidated through the generation of sophisticated tissue-specific gene knockout mouse models.[citation needed]

References

  1. 1.0 1.1 1.2 "The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis". Proceedings of the National Academy of Sciences of the United States of America 101 (17): 6472–7. April 2004. doi:10.1073/pnas.0308686101. PMID 15087503. Bibcode2004PNAS..101.6472S. 
  2. 2.0 2.1 "Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense". Genes & Development 21 (15): 1909–20. August 2007. doi:10.1101/gad.1553007. PMID 17671090. 
  3. "Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) coactivates the cardiac-enriched nuclear receptors estrogen-related receptor-alpha and -gamma. Identification of novel leucine-rich interaction motif within PGC-1alpha". The Journal of Biological Chemistry 277 (43): 40265–74. October 2002. doi:10.1074/jbc.M206324200. PMID 12181319. 
  4. "A polymorphic autoregulatory hormone response element in the human estrogen-related receptor alpha (ERRalpha) promoter dictates peroxisome proliferator-activated receptor gamma coactivator-1alpha control of ERRalpha expression". The Journal of Biological Chemistry 279 (18): 18504–10. April 2004. doi:10.1074/jbc.M313543200. PMID 14978033. 
  5. "The transcriptional coactivator PGC-1 regulates the expression and activity of the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha)". The Journal of Biological Chemistry 278 (11): 9013–8. March 2003. doi:10.1074/jbc.M212923200. PMID 12522104. 
  6. 6.0 6.1 "Transcriptional control of energy homeostasis by the estrogen-related receptors". Endocrine Reviews 29 (6): 677–96. October 2008. doi:10.1210/er.2008-0017. PMID 18664618. 
  7. "The orphan nuclear receptor estrogen-related receptor alpha is a transcriptional regulator of the human medium-chain acyl coenzyme A dehydrogenase gene". Molecular and Cellular Biology 17 (9): 5400–9. September 1997. doi:10.1128/mcb.17.9.5400. PMID 9271417. 
  8. "Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle". Proceedings of the National Academy of Sciences of the United States of America 101 (17): 6570–5. April 2004. doi:10.1073/pnas.0401401101. PMID 15100410. Bibcode2004PNAS..101.6570M. 
  9. "The nuclear receptor ERRalpha is required for the bioenergetic and functional adaptation to cardiac pressure overload". Cell Metabolism 6 (1): 25–37. July 2007. doi:10.1016/j.cmet.2007.06.005. PMID 17618854. 
  10. "ERRgamma directs and maintains the transition to oxidative metabolism in the postnatal heart". Cell Metabolism 6 (1): 13–24. July 2007. doi:10.1016/j.cmet.2007.06.007. PMID 17618853. 
  11. "Estrogen-related receptor α (ERRα) and ERRγ are essential coordinators of cardiac metabolism and function". Molecular and Cellular Biology 35 (7): 1281–98. April 2015. doi:10.1128/MCB.01156-14. PMID 25624346. 
  12. "Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma". Cell Metabolism 5 (5): 345–56. May 2007. doi:10.1016/j.cmet.2007.03.007. PMID 17488637. 
  13. "Orphan nuclear receptor estrogen-related receptor alpha is essential for adaptive thermogenesis". Proceedings of the National Academy of Sciences of the United States of America 104 (4): 1418–23. January 2007. doi:10.1073/pnas.0607696104. PMID 17229846. Bibcode2007PNAS..104.1418V. 
  14. "Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge". Nature 546 (7659): 544–548. June 2017. doi:10.1038/nature22819. PMID 28614293. Bibcode2017Natur.546..544E. 
  15. "ERRγ enhances UCP1 expression and fatty acid oxidation in brown adipocytes". Obesity 21 (3): 516–24. March 2013. doi:10.1002/oby.20067. PMID 23404793. 
  16. "Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor alpha". Molecular and Cellular Biology 23 (22): 7947–56. November 2003. doi:10.1128/MCB.23.22.7947-7956.2003. PMID 14585956. 
  17. "Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-beta". Nature 388 (6644): 778–82. August 1997. doi:10.1038/42022. PMID 9285590. Bibcode1997Natur.388..778L. 
  18. "Estrogen-related receptors as emerging targets in cancer and metabolic disorders". Current Topics in Medicinal Chemistry 6 (3): 203–15. 2006. doi:10.2174/156802606776173483. PMID 16515477. 

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