Estrogen-related receptor-β

Target id: 623

Nomenclature: Estrogen-related receptor-β

Systematic Nomenclature: NR3B2

Family: 3B. Estrogen-related receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for Estrogen-related receptor-β in GtoImmuPdb

Gene and Protein Information
Species AA Chromosomal Location Gene Symbol Gene Name Reference
Human 508 14q24.3 ESRRB estrogen related receptor beta 1
Mouse 433 12E Esrrb estrogen related receptor, beta 5
Rat 433 6q31 Esrrb estrogen-related receptor beta 5
Previous and Unofficial Names
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
Database Links
Specialist databases
NURSA Receptor 10.1621/KPUFMIYQ99 (Hs)
Other databases
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
Comments: Orphan

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
genistein Hs Agonist - - 6
[6]
daidzein Hs Agonist - - 6
[6]
biochanin A Hs Agonist - - 6
[6]
DY131 Hs Agonist - - 9
[9]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
diethylstilbestrol Hs Antagonist 4.8 – 5.3 pIC50 7
pIC50 4.8 – 5.3 [7]
DNA Binding
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
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
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
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
ERRβ Null Mice: show severely impaired placental formation.
Species:  Mouse
Tissue: 
Technique:  Knock Out
References:  3
Phenotypes, Alleles and Disease Models 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
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
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. Gene228 (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. Nature331 (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. Nature388 (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 17/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=623.