Estrogen-related receptor

Last updated
estrogen-related receptor alpha
Identifiers
Symbol ESRRA
Alt. symbolsESRL1
NCBI gene 2101
HGNC 3471
OMIM 601998
RefSeq NM_004451
UniProt P11474
Other data
Locus Chr. 11 q12
Search for
Structures Swiss-model
Domains InterPro
estrogen-related receptor beta
Identifiers
Symbol ESRRB
Alt. symbolsESRL2
NCBI gene 2103
HGNC 3473
OMIM 602167
RefSeq NM_004452
UniProt O95718
Other data
Locus Chr. 14 q24.3
Search for
Structures Swiss-model
Domains InterPro
estrogen-related receptor gamma
Identifiers
Symbol ESRRG
NCBI gene 2104
HGNC 3474
OMIM 602969
RefSeq NM_206595
UniProt P62508
Other data
Locus Chr. 1 q41
Search for
Structures Swiss-model
Domains InterPro

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 ]

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<span class="mw-page-title-main">RAR-related orphan receptor alpha</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Estrogen-related receptor beta</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Estrogen-related receptor gamma</span> Protein-coding gene in the species Homo sapiens

Estrogen-related receptor gamma (ERR-gamma), also known as NR3B3, is a nuclear receptor that in humans is encoded by the ESRRG gene. It behaves as a constitutive activator of transcription.

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<span class="mw-page-title-main">Estrogen-related receptor alpha</span> Protein-coding gene in the species Homo sapiens

Estrogen-related receptor alpha (ERRα), also known as NR3B1, is a nuclear receptor that in humans is encoded by the ESRRA gene. ERRα was originally cloned by DNA sequence homology to the estrogen receptor alpha, but subsequent ligand binding and reporter-gene transfection experiments demonstrated that estrogens did not regulate ERRα. Currently, ERRα is considered an orphan nuclear receptor.

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<span class="mw-page-title-main">TRIM24</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">MED16</span> Protein-coding gene in the species Homo sapiens

Mediator of RNA polymerase II transcription subunit 16 is an enzyme that in humans is encoded by the MED16 gene.

<span class="mw-page-title-main">PNRC1</span> Protein-coding gene in the species Homo sapiens

Proline-rich nuclear receptor coactivator 1 is a protein that, in humans, is encoded by the PNRC1 gene.

<span class="mw-page-title-main">NCOA5</span> Gene of the species Homo sapiens

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Mitochondrial biogenesis is the process by which cells increase mitochondrial numbers. It was first described by John Holloszy in the 1960s, when it was discovered that physical endurance training induced higher mitochondrial content levels, leading to greater glucose uptake by muscles. Mitochondrial biogenesis is activated by numerous different signals during times of cellular stress or in response to environmental stimuli, such as aerobic exercise.

References

  1. 1 2 3 Schreiber SN, Emter R, Hock MB, Knutti D, Cardenas J, Podvinec M, Oakeley EJ, Kralli A (April 2004). "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. Bibcode:2004PNAS..101.6472S. doi: 10.1073/pnas.0308686101 . PMC   404069 . PMID   15087503.
  2. 1 2 Sonoda J, Laganière J, Mehl IR, Barish GD, Chong LW, Li X, Scheffler IE, Mock DC, Bataille AR, Robert F, Lee CH, Giguère V, Evans RM (August 2007). "Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense". Genes & Development. 21 (15): 1909–20. doi:10.1101/gad.1553007. PMC   1935029 . PMID   17671090.
  3. ↑ Huss JM, Kopp RP, Kelly DP (October 2002). "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. doi: 10.1074/jbc.M206324200 . PMID   12181319.
  4. ↑ Laganière J, Tremblay GB, Dufour CR, Giroux S, Rousseau F, Giguère V (April 2004). "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. doi: 10.1074/jbc.M313543200 . PMID   14978033.
  5. ↑ Schreiber SN, Knutti D, Brogli K, Uhlmann T, Kralli A (March 2003). "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. doi: 10.1074/jbc.M212923200 . PMID   12522104.
  6. 1 2 Giguère V (October 2008). "Transcriptional control of energy homeostasis by the estrogen-related receptors". Endocrine Reviews. 29 (6): 677–96. doi:10.1210/er.2008-0017. PMID   18664618.
  7. ↑ Sladek R, Bader JA, Giguère V (September 1997). "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. doi:10.1128/mcb.17.9.5400. PMC   232390 . PMID   9271417.
  8. ↑ Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D, Puigserver P, Patterson N, Willy PJ, Schulman IG, Heyman RA, Lander ES, Spiegelman BM (April 2004). "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. Bibcode:2004PNAS..101.6570M. doi: 10.1073/pnas.0401401101 . PMC   404086 . PMID   15100410.
  9. ↑ Huss JM, Imahashi K, Dufour CR, Weinheimer CJ, Courtois M, Kovacs A, Giguère V, Murphy E, Kelly DP (July 2007). "The nuclear receptor ERRalpha is required for the bioenergetic and functional adaptation to cardiac pressure overload". Cell Metabolism. 6 (1): 25–37. doi: 10.1016/j.cmet.2007.06.005 . PMID   17618854.
  10. ↑ Alaynick WA, Kondo RP, Xie W, He W, Dufour CR, Downes M, Jonker JW, Giles W, Naviaux RK, Giguère V, Evans RM (July 2007). "ERRgamma directs and maintains the transition to oxidative metabolism in the postnatal heart". Cell Metabolism. 6 (1): 13–24. doi: 10.1016/j.cmet.2007.06.007 . PMID   17618853.
  11. ↑ Wang T, McDonald C, Petrenko NB, Leblanc M, Wang T, Giguere V, Evans RM, Patel VV, Pei L (April 2015). "Estrogen-related receptor α (ERRα) and ERRγ are essential coordinators of cardiac metabolism and function". Molecular and Cellular Biology. 35 (7): 1281–98. doi:10.1128/MCB.01156-14. PMC   4355525 . PMID   25624346.
  12. ↑ Dufour CR, Wilson BJ, Huss JM, Kelly DP, Alaynick WA, Downes M, Evans RM, Blanchette M, Giguère V (May 2007). "Genome-wide orchestration of cardiac functions by the orphan nuclear receptors ERRalpha and gamma". Cell Metabolism. 5 (5): 345–56. doi: 10.1016/j.cmet.2007.03.007 . PMID   17488637.
  13. ↑ Villena JA, Hock MB, Chang WY, Barcas JE, Giguère V, Kralli A (January 2007). "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. Bibcode:2007PNAS..104.1418V. doi: 10.1073/pnas.0607696104 . PMC   1783094 . PMID   17229846.
  14. ↑ Emmett MJ, Lim HW, Jager J, Richter HJ, Adlanmerini M, Peed LC, Briggs ER, Steger DJ, Ma T, Sims CA, Baur JA, Pei L, Won KJ, Seale P, Gerhart-Hines Z, Lazar MA (June 2017). "Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge". Nature. 546 (7659): 544–548. Bibcode:2017Natur.546..544E. doi:10.1038/nature22819. PMC   5826652 . PMID   28614293.
  15. ↑ Dixen K, Basse AL, Murholm M, Isidor MS, Hansen LH, Petersen MC, Madsen L, Petrovic N, Nedergaard J, Quistorff B, Hansen JB (March 2013). "ERRγ enhances UCP1 expression and fatty acid oxidation in brown adipocytes". Obesity. 21 (3): 516–24. doi:10.1002/oby.20067. PMID   23404793. S2CID   206317418.
  16. ↑ Luo J, Sladek R, Carrier J, Bader JA, Richard D, Giguère V (November 2003). "Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor alpha". Molecular and Cellular Biology. 23 (22): 7947–56. doi:10.1128/MCB.23.22.7947-7956.2003. PMC   262360 . PMID   14585956.
  17. ↑ Luo J, Sladek R, Bader JA, Matthyssen A, Rossant J, Giguère V (August 1997). "Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-beta". Nature. 388 (6644): 778–82. Bibcode:1997Natur.388..778L. doi: 10.1038/42022 . PMID   9285590. S2CID   4371787.
  18. ↑ Ariazi EA, Jordan VC (2006). "Estrogen-related receptors as emerging targets in cancer and metabolic disorders". Current Topics in Medicinal Chemistry. 6 (3): 203–15. doi:10.2174/156802606776173483. PMID   16515477.
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