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Estrogen-related receptor-β

Systematic Nomenclature: NR3B2

Family: 3B. Estrogen-related receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
DNA Binding
Co-binding Partners
Main Co-regulators
Tissue Distribution
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
Biologically Significant Variants
References
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
ERR2
ERRb
ESRL2
estrogen-related receptor β
estrogen receptor-like 2
DFNB35
ERRbeta
NR3B2
deafness, autosomal recessive 35
ERR-beta
estrogen-related receptor, beta
nuclear receptor subfamily 3 group B member 2
steroid hormone receptor ERR2
Estrrb
Database Links
ChEMBL Target 11254 (Hs)
Ensembl ENSG00000119715 (Hs), ENSMUSG00000021255 (Mm), ENSRNOG00000010259 (Rn)
Entrez Gene 2103 (Hs), 26380 (Mm), 299210 (Rn)
GeneCards ESRRB (Hs)
GenitoUrinary Development Molecular Anatomy Project Esrrb (Mm)
HomoloGene 69108 (Hs)
Human Protein Reference Database 03700 (Hs)
InterPro O95718 (Hs), Q61539 (Mm), P11475 (Rn)
KEGG Gene hsa:2103 (Hs), mmu:26380 (Mm), rno:299210 (Rn)
NURSA Receptor 3B2
OMIM 602167 (Hs)
Orphanet Gene ORPHA160244 (Hs)
PharmGKB Gene PA27889 (Hs)
PhosphoSitePlus O95718 (Hs), Q61539 (Mm), P11475 (Rn)
RefSeq Nucleotide NM_004452 (Hs), NM_001159500 (Mm), NM_011934 (Mm), NM_001008516 (Rn)
RefSeq Protein NP_004443 (Hs), NP_036064 (Mm), NP_001008516 (Rn)
TreeFam ENSG00000119715 (Hs), ENSMUSG00000021255 (Mm), ENSRNOG00000010259 (Rn)
UniProt O95718 (Hs), Q61539 (Mm), P11475 (Rn)
Orphan nuclear receptors
Search for 3D structures on the PDB
Search by keyword: Estrogen-related receptor-β Search by accession number: O95718, P11475, Q61539
Natural/Endogenous Ligand(s)
Comments: Orphan
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
5,7-dihydroxy-4'-methoxyisoflavone Hs Agonist - - 6
7,4'-dihydroxyisoflavone Hs Agonist - - 6
DY131 Hs Agonist - - 9
genistein Hs Agonist - - 6
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
diethylstilbestrol Hs Antagonist 5.3 – 4.8 pIC50 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

Click here to show/hide data

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:  Autosomal recessive deafness 35
OMIM:  608565
Orphanet:  90636
References: 
Mutations not determined
Biologically Significant Variants
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.
Type:  Splice variant
Species:  Human
References:  10
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
Type:  Splice variant
Species:  Human
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]

To cite this database page, please use the following:

3B. Estrogen-related receptors: Estrogen-related receptor-β. Last modified on 08/05/2012. Accessed on 18/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=623.


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