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Target not currently curated in GtoImmuPdb
Target id: 624
Nomenclature: Estrogen-related receptor-γ
Systematic Nomenclature: NR3B3
Family: 3B. Estrogen-related receptors
Gene and Protein Information  |
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| Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 458 | 1q41 | ESRRG | estrogen related receptor gamma | 4,10 |
| Mouse | 458 | 1 H5-H6 | Esrrg | estrogen-related receptor gamma | 10 |
| Rat | 458 | 13q26 | Esrrg | estrogen-related receptor gamma | 14 |
| Previous and Unofficial Names |
| ERRγ | ESRL3 | estrogen receptor-like 3 | nuclear receptor subfamily 3 group B member 3 | estrogen-related receptor 3 | ERR3 |
| Database Links |
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| Alphafold | P62508 (Hs), P62509 (Mm), P62510 (Rn) |
| CATH/Gene3D | 3.30.50.10 |
| ChEMBL Target | CHEMBL4245 (Hs), CHEMBL3585238 (Mm) |
| DrugBank Target | P62508 (Hs) |
| Ensembl Gene | ENSG00000196482 (Hs), ENSMUSG00000026610 (Mm), ENSRNOG00000002593 (Rn) |
| Entrez Gene | 2104 (Hs), 26381 (Mm), 360896 (Rn) |
| Human Protein Atlas | ENSG00000196482 (Hs) |
| KEGG Gene | hsa:2104 (Hs), mmu:26381 (Mm), rno:360896 (Rn) |
| OMIM | 602969 (Hs) |
| Pharos | P62508 (Hs) |
| RefSeq Nucleotide | NM_206595 (Hs), NM_001243792 (Mm), NM_011935 (Mm), NM_203336 (Rn) |
| RefSeq Protein | NP_001429 (Hs), NP_996318 (Hs), NP_996317 (Hs), NP_036065 (Mm), NP_976081 (Rn) |
| SynPHARM |
6548 (in complex with 4-hydroxytamoxifen) 83095 (in complex with 4-hydroxytamoxifen) 83094 (in complex with GSK5182) |
| UniProtKB | P62508 (Hs), P62509 (Mm), P62510 (Rn) |
| Wikipedia | ESRRG (Hs) |
| Selected 3D Structures |
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| Natural/Endogenous Ligands |
| Comments: Orphan |
Download all structure-activity data for this target as a CSV file 
| Agonists |
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| The identification of the flavinoids compounds as ERRα agonist is based on cell transfection reporter assay and on mammalian two hibryd assays (PNRC2 induced recruitment). DY131 selectively activates ERRβ and γ. GSK4716 and GSK9089 binding affinity were measured by FRET. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonists |
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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| DNA Binding |
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| DNA Binding Comments | |||||||
| ERRγ was shown to bind to the ERE as well as to the SFRE (SF1 Response Elements: TNA AGGTCA) and EREs, in vitro. Data suggest that ERR interaction with EREs does not occur in vivo (V. Giguère, personal communication). Importantly, ERRγ homodimerization seems to enhance its transcriptional activity [11]. | |||||||
| Co-binding Partners |
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| Name | Interaction | Effect | Reference |
| DAX1 | Physical, Functional | DAX-1 inhibited PGC-1α mediated ERRγ transactivation, via competition between these two factors for the AF-2 binding domain. | 13 |
| SHP | Physical, Functional | SHP interaction with ERRγ inhibits its transcriptional activity | 14 |
| Calmodulin | Physical, Functional | Calmodulin and ERRγ interact in vitro in Ca2+ dependent manner and transient transfection analysis revealed a Ca2+-influx-dependent ERRγ-mediated transcriptional activation of a luciferase reporter gene. | 8 |
| Main Co-regulators |
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| Name | Activity | Specific | Ligand dependent | AF-2 dependent | Comments | References |
| PNRC2 | Co-activator | No | Yes | Yes | 7 | |
| PPARGC1A | Co-activator | No | No | Yes | 9 | |
| PPARGC1B | Co-activator | No | No | Yes | 9 | |
| NCOA1 | Co-activator | No | No | Yes | 5 | |
| TLE1 | Co-activator | - | No | - | 7 | |
| Main Co-regulators Comments | ||||||
| TLE1 previously known as a corepressor, interacts with ERRγ AF-1 and acts as a coactivator. | ||||||
| Main Target Genes |
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| Name | Species | Effect | Technique | Comments | References |
| NR3B1 | Human | Activated | ChIP, Transient transfection, EMSA, Other | ERRγ activates ERRα expression via a conserved multi-hormone response element. | 12 |
| MAOA | Human | Activated | ChIP, Transient transfection, EMSA, Other | 20 | |
| MOAB | Human | Activated | ChIP, Transient transfection, EMSA | 20 | |
| Nr0b1 | Mouse | Activated | ChIP, Transient transfection, EMSA | 13 | |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| Similar patterns seen in mice. And different studies are not in accordance for the expression in heart but this may be linked to the differential expression of transcripts coding for specific isoforms. Some studies have reported an absence of expression in 7 days post coitum mouse embryos and a high expression at 11, 15 and 17 days. This suggests that in contrast to ERRα and ERRβ, ERRγ is not expressed during early embryogenesis. | ||||||||
| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Biologically Significant Variants
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1. Chao EY, Collins JL, Gaillard S, Miller AB, Wang L, Orband-Miller LA, Nolte RT, McDonnell DP, Willson TM, Zuercher WJ. (2006) Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRgamma. Bioorg Med Chem Lett, 16 (4): 821-4. [PMID:16307879]
2. Chen F, Zhang Q, McDonald T, Davidoff MJ, Bailey W, Bai C, Liu Q, Caskey CT. (1999) Identification of two hERR2-related novel nuclear receptors utilizing bioinformatics and inverse PCR. Gene, 228 (1-2): 101-9. [PMID:10072763]
3. Coward P, Lee D, Hull MV, Lehmann JM. (2001) 4-Hydroxytamoxifen binds to and deactivates the estrogen-related receptor gamma. Proc Natl Acad Sci USA, 98 (15): 8880-4. [PMID:11447273]
4. Eudy JD, Yao S, Weston MD, Ma-Edmonds M, Talmadge CB, Cheng JJ, Kimberling WJ, Sumegi J. (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. [PMID:9676434]
5. Greschik H, Wurtz JM, Sanglier S, Bourguet W, van Dorsselaer A, Moras D, Renaud JP. (2002) Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3. Mol Cell, 9 (2): 303-13. [PMID:11864604]
6. Heard DJ, Norby PL, Holloway J, Vissing H. (2000) 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. Mol Endocrinol, 14 (3): 382-92. [PMID:10707956]
7. Hentschke M, Borgmeyer U. (2003) Identification of PNRC2 and TLE1 as activation function-1 cofactors of the orphan nuclear receptor ERRgamma. Biochem Biophys Res Commun, 312 (4): 975-82. [PMID:14651967]
8. Hentschke M, Schulze C, Süsens U, Borgmeyer U. (2003) Characterization of calmodulin binding to the orphan nuclear receptor Errgamma. Biol Chem, 384 (3): 473-82. [PMID:12715898]
9. Hentschke M, Süsens U, Borgmeyer U. (2002) PGC-1 and PERC, coactivators of the estrogen receptor-related receptor gamma. Biochem Biophys Res Commun, 299 (5): 872-9. [PMID:12470660]
10. Hong H, Yang L, Stallcup MR. (1999) Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERR3. J Biol Chem, 274 (32): 22618-26. [PMID:10428842]
11. Huppunen J, Aarnisalo P. (2004) Dimerization modulates the activity of the orphan nuclear receptor ERRgamma. Biochem Biophys Res Commun, 314 (4): 964-70. [PMID:14751226]
12. Liu D, Zhang Z, Teng CT. (2005) 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. J Mol Endocrinol, 34 (2): 473-87. [PMID:15821111]
13. Park YY, Ahn SW, Kim HJ, Kim JM, Lee IK, Kang H, Choi HS. (2005) An autoregulatory loop controlling orphan nuclear receptor DAX-1 gene expression by orphan nuclear receptor ERRgamma. Nucleic Acids Res, 33 (21): 6756-68. [PMID:16314306]
14. Razzaque MA, Masuda N, Maeda Y, Endo Y, Tsukamoto T, Osumi T. (2004) Estrogen receptor-related receptor gamma has an exceptionally broad specificity of DNA sequence recognition. Gene, 340 (2): 275-82. [PMID:15475169]
15. Suetsugi M, Su L, Karlsberg K, Yuan YC, Chen S. (2003) Flavone and isoflavone phytoestrogens are agonists of estrogen-related receptors. Mol Cancer Res, 1 (13): 981-91. [PMID:14638870]
16. Süsens U, Hermans-Borgmeyer I, Borgmeyer U. (2000) Alternative splicing and expression of the mouse estrogen receptor-related receptor gamma. Biochem Biophys Res Commun, 267 (2): 532-5. [PMID:10631096]
17. Tremblay GB, Kunath T, Bergeron D, Lapointe L, Champigny C, Bader JA, Rossant J, Giguère V. (2001) Diethylstilbestrol regulates trophoblast stem cell differentiation as a ligand of orphan nuclear receptor ERR beta. Genes Dev, 15 (7): 833-8. [PMID:11297507]
18. Wang L, Zuercher WJ, Consler TG, Lambert MH, Miller AB, Orband-Miller LA, McKee DD, Willson TM, Nolte RT. (2006) 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, 281 (49): 37773-81. [PMID:16990259]
19. Yu DD, Forman BM. (2005) Identification of an agonist ligand for estrogen-related receptors ERRbeta/gamma. Bioorg Med Chem Lett, 15 (5): 1311-3. [PMID:15713377]
20. Zhang Z, Chen K, Shih JC, Teng CT. (2006) Estrogen-related receptors-stimulated monoamine oxidase B promoter activity is down-regulated by estrogen receptors. Mol Endocrinol, 20 (7): 1547-61. [PMID:16484337]
21. Zuercher WJ, Gaillard S, Orband-Miller LA, Chao EY, Shearer BG, Jones DG, Miller AB, Collins JL, McDonnell DP, Willson TM. (2005) Identification and structure-activity relationship of phenolic acyl hydrazones as selective agonists for the estrogen-related orphan nuclear receptors ERRbeta and ERRgamma. J Med Chem, 48 (9): 3107-9. [PMID:15857113]
3B. Estrogen-related receptors: Estrogen-related receptor-γ. Last modified on 06/11/2015. Accessed on 11/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=624.
