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Estrogen-related receptor-β

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Target not currently curated in GtoImmuPdb

Target id: 623

Nomenclature: Estrogen-related receptor-β

Systematic Nomenclature: NR3B2

Family: 3B. Estrogen-related receptors

Gene and Protein Information Click here for help
Species AA Chromosomal Location Gene Symbol Gene Name Reference
Human 433 14q24.3 ESRRB estrogen related receptor beta 1
Mouse 433 12 40.49 cM Esrrb estrogen related receptor, beta 5
Rat 433 6q31 Esrrb estrogen-related receptor beta 5
Previous and Unofficial Names Click here for help
ERRβ | ESRL2 | estrogen receptor-like 2 | estrogen-related receptor β | DFNB35 | deafness, autosomal recessive 35 | nuclear receptor subfamily 3 group B member 2 | steroid hormone receptor ERR2 | estrogen-related receptor beta | estrogen related receptor, beta | estrogen related receptor
Database Links Click here for help
Alphafold
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
Comments: Orphan

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists Click here for help
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
genistein Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Agonist - - 6
[6]
daidzein Small molecule or natural product Click here for species-specific activity table Hs Agonist - - 6
[6]
biochanin A Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Agonist - - 6
[6]
DY131 Small molecule or natural product Click here for species-specific activity table Hs Agonist - - 9
[9]
Antagonists Click here for help
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
diethylstilbestrol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.8 – 5.3 pIC50 7
pIC50 4.8 – 5.3 [7]
DNA Binding Click here for help
Structure:  Monomer, Homodimer
HRE core sequence:  TNA AGGTCA
Response element:  DR3, ERE, Half site, Other - see comments
DNA Binding Comments
ERRα and β bind SFREs (SF1 Response Elements: TNA AGGTCA) and EREs (Estrogen Responsive Elements) in vitro and that ERRα interact with these elements as a dimer. Interestingly, ERRs recognized only a subset of EREs. For example ERRα recognize EREs presenting the sequence AG AGGTCA NNN TGACCT CT whereas ERRβ recognize (C/A)G AGGTCA NNN TGACCT G(C/A). In vivo data and large scale analysis of promoter binding indicate that ERRβ interact with SFREs (V. Giguère, personal communication).
Co-binding Partners Click here for help
Name Interaction Effect Reference
Hsp90 Physical, Functional DNA Binding: Efficient homodimerization and DNA-binding of ERRβ is dependent on interaction with the heat shock protein 90 (Hsp90) 5
Main Co-regulators Click here for help
Name Activity Specific Ligand dependent AF-2 dependent Comments References
PNRC1 Co-activator No Yes Yes 6
NCOA3 Co-activator No No Yes 8
NCOA2 Co-activator No No Yes 8
NCOA1 Co-activator No No Yes 8
Tissue Distribution Click here for help
Adult tissue (liver, stomach, skeletal muscles, kidney and heart) and embryonic (trophoblast progenitor cells)
Species:  Mouse
Technique:  Northern, in situ, Western, immunohistology, other
References:  1-2,4-5,10
Physiological Consequences of Altering Gene Expression Click here for help
ERRβ Null Mice: show severely impaired placental formation.
Species:  Mouse
Tissue: 
Technique:  Knock Out
References:  3
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0002836 abnormal chorion morphology PMID: 9285590 
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0002086 abnormal extraembryonic tissue morphology PMID: 9285590 
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0001711 abnormal placenta morphology PMID: 9285590 
Esrrbtm1.1Nat|Esrrbtm1.2Nat|Tg(Sox2-cre)1Amc Esrrbtm1.1Nat/Esrrbtm1.2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL
MGI:1346832  MGI:2656537  MP:0003169 abnormal scala media morphology PMID: 17765677 
Esrrbtm1.1Nat|Esrrbtm1.2Nat|Tg(Sox2-cre)1Amc Esrrbtm1.1Nat/Esrrbtm1.2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL
MGI:1346832  MGI:2656537  MP:0002428 abnormal semicircular canal PMID: 17765677 
Esrrbtm1.1Nat|Esrrbtm1.2Nat|Tg(Sox2-cre)1Amc Esrrbtm1.1Nat/Esrrbtm1.2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL
MGI:1346832  MGI:2656537  MP:0008488 abnormal semicircular canal ampulla morphology PMID: 17765677 
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0004255 abnormal spongiotrophoblast layer morphology PMID: 9285590 
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0005033 abnormal trophoblast giant cells PMID: 9285590 
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0005031 abnormal trophoblast layer morphology PMID: 9285590 
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0009593 absent chorion PMID: 9285590 
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0003403 absent placental labyrinth PMID: 9285590 
Esrrbtm1.1Nat|Esrrbtm1.2Nat|Tg(Sox2-cre)1Amc Esrrbtm1.1Nat/Esrrbtm1.2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL
MGI:1346832  MGI:2656537  MP:0006359 absent startle reflex PMID: 17765677 
Esrrbtm1.1Nat|Esrrbtm1.2Nat|Tg(Nes-cre)1Kln Esrrbtm1.1Nat/Esrrbtm1.2Nat,Tg(Nes-cre)1Kln/0
involves: 129S6/SvEvTac * C57BL/6 * SJL
MGI:1346832  MGI:2176172  MP:0004758 absent strial marginal cells PMID: 17765677 
Esrrbtm1.1Nat|Esrrbtm1.2Nat|Tg(Sox2-cre)1Amc Esrrbtm1.1Nat/Esrrbtm1.2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL
MGI:1346832  MGI:2656537  MP:0001394 circling PMID: 17765677 
Esrrbtm1.1Nat|Esrrbtm1.2Nat|Tg(Nes-cre)1Kln Esrrbtm1.1Nat/Esrrbtm1.2Nat,Tg(Nes-cre)1Kln/0
involves: 129S6/SvEvTac * C57BL/6 * SJL
MGI:1346832  MGI:2176172  MP:0004765 decreased brainstem auditory evoked potential PMID: 17765677 
Esrrbtm1.1Nat|Esrrbtm1.2Nat|Tg(Sox2-cre)1Amc Esrrbtm1.1Nat/Esrrbtm1.2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL
MGI:1346832  MGI:2656537  MP:0004765 decreased brainstem auditory evoked potential PMID: 17765677 
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0001698 decreased embryo size PMID: 9285590 
Esrrbtm1.1Nat|Esrrbtm1.2Nat|Tg(Sox2-cre)1Amc Esrrbtm1.1Nat/Esrrbtm1.2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL
MGI:1346832  MGI:2656537  MP:0004887 decreased endolymph production PMID: 17765677 
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0001713 decreased trophoblast giant cell number PMID: 9285590 
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0003988 disorganized embryonic tissue PMID: 9285590 
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0003984 embryonic growth retardation PMID: 9285590 
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0006207 embryonic lethality during organogenesis PMID: 9285590 
Esrrbtm1Vgi Esrrbtm1Vgi/Esrrbtm1Vgi
involves: 129S1/Sv * 129X1/SvJ
MGI:1346832  MP:0009657 failure of chorioallantoic fusion PMID: 9285590 
Esrrbtm1.1Nat|Esrrbtm1.2Nat|Tg(Sox2-cre)1Amc Esrrbtm1.1Nat/Esrrbtm1.2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL
MGI:1346832  MGI:2656537  MP:0001410 head bobbing PMID: 17765677 
Esrrbtm1.2Nat Esrrbtm1.2Nat/Esrrbtm1.2Nat
involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL
MGI:1346832  MP:0002080 prenatal lethality PMID: 17765677 
Esrrbtm1.1Nat|Esrrbtm1.2Nat|Tg(Sox2-cre)1Amc Esrrbtm1.1Nat/Esrrbtm1.2Nat,Tg(Sox2-cre)1Amc/0
involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL
MGI:1346832  MGI:2656537  MP:0008308 small scala media PMID: 17765677 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Deafness, autosomal recessive 35; DFNB35
Synonyms: Autosomal recessive nonsyndromic deafness [Disease Ontology: DOID:0050565]
Autosomal recessive non-syndromic sensorineural deafness type DFNB [Orphanet: ORPHA90636]
Disease Ontology: DOID:0050565
OMIM: 608565
Orphanet: ORPHA90636
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  hERR β2-δ10: lacks exon 10 present in canonical transcript and encodes a protein isoform only differing in the F domain of the protein. Species: 1Human References:8
References:  10
Type:  Splice variant
Species:  Human
Description:  Short-form hERRβ: This splicing variant lacks the F domain found in hERR β and is the matched homologomouse and rat ERR proteins in humans.
References:  10
Biologically Significant Variant Comments
Short-form hERRβ is widely expressed whereas other isoforms are restricted to testis and kidney.

References

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1. 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]

2. Giguère V, Yang N, Segui P, Evans RM. (1988) Identification of a new class of steroid hormone receptors. Nature, 331 (6151): 91-4. [PMID:3267207]

3. Luo J, Sladek R, Bader JA, Matthyssen A, Rossant J, Giguère V. (1997) Placental abnormalities in mouse embryos lacking the orphan nuclear receptor ERR-beta. Nature, 388 (6644): 778-82. [PMID:9285590]

4. Luo J, Sladek R, Carrier J, Bader JA, Richard D, Giguère V. (2003) Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor alpha. Mol Cell Biol, 23 (22): 7947-56. [PMID:14585956]

5. Pettersson K, Svensson K, Mattsson R, Carlsson B, Ohlsson R, Berkenstam A. (1996) Expression of a novel member of estrogen response element-binding nuclear receptors is restricted to the early stages of chorion formation during mouse embryogenesis. Mech Dev, 54 (2): 211-23. [PMID:8652414]

6. 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]

7. 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]

8. Xie W, Hong H, Yang NN, Lin RJ, Simon CM, Stallcup MR, Evans RM. (1999) Constitutive activation of transcription and binding of coactivator by estrogen-related receptors 1 and 2. Mol Endocrinol, 13 (12): 2151-62. [PMID:10598588]

9. 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]

10. Zhou W, Liu Z, Wu J, Liu JH, Hyder SM, Antoniou E, Lubahn DB. (2006) Identification and characterization of two novel splicing isoforms of human estrogen-related receptor beta. J Clin Endocrinol Metab, 91 (2): 569-79. [PMID:16332939]

How to cite this page

3B. Estrogen-related receptors: Estrogen-related receptor-β. Last modified on 23/10/2014. Accessed on 19/10/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=623.