Q61539 · ERR2_MOUSE

  • Protein
    Steroid hormone receptor ERR2
  • Gene
    Esrrb
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcriptional activity (PubMed:18662995, PubMed:18957414, PubMed:20534447, PubMed:23019124, PubMed:23169531, PubMed:23508100, PubMed:26206133, PubMed:27601327, PubMed:27723719).
Plays a role, in a LIF-independent manner, in maintainance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF signaling pathway and Wnt signaling pathways (PubMed:18957414, PubMed:20534447, PubMed:23019124, PubMed:23040477, PubMed:23040478, PubMed:23169531, PubMed:26206133).
Upon FGF signaling pathway activation, interacts with KDM1A by directly binding to enhancer site of ELF5 and EOMES and activating their transcription leading to self-renewal of trophoblast stem cells (PubMed:26206133).
Also regulates expression of multiple rod-specific genes and is required for survival of this cell type (PubMed:20534447).
Plays a role as transcription factor activator of GATA6, NR0B1, POU5F1 and PERM1 (PubMed:18662995, PubMed:18957414, PubMed:23508100).
Plays a role as transcription factor repressor of NFE2L2 transcriptional activity and ESR1 transcriptional activity (By similarity).
During mitosis remains bound to a subset of interphase target genes, including pluripotency regulators, through the canonical ESRRB recognition (ERRE) sequence, leading to their transcriptional activation in early G1 phase (PubMed:27723719).
Can coassemble on structured DNA elements with other transcription factors like SOX2, POU5F1, KDM1A and NCOA3 to trigger ESRRB-dependent gene activation (PubMed:18662995, PubMed:23019124, PubMed:23169531, PubMed:26206133).
This mechanism, in the case of SOX2 corecruitment prevents the embryonic stem cells (ESCs) to epiblast stem cells (EpiSC) transition through positive regulation of NR0B1 that inhibits the EpiSC transcriptional program (PubMed:23169531).
Also plays a role inner ear development by controlling expression of ion channels and transporters and in early placentation (PubMed:17765677, PubMed:9285590).

Features

Showing features for dna binding, site.

TypeIDPosition(s)Description
DNA binding100-186Nuclear receptor
Site185Important for stabilizing DNA-binding

GO annotations

AspectTerm
Cellular Componentchromatin
Cellular Componentcondensed chromosome
Cellular Componentcytoplasm
Cellular Componentnucleus
Molecular Functioncis-regulatory region sequence-specific DNA binding
Molecular FunctionDNA-binding transcription activator activity, RNA polymerase II-specific
Molecular FunctionDNA-binding transcription factor activity
Molecular FunctionDNA-binding transcription factor activity, RNA polymerase II-specific
Molecular Functionestrogen response element binding
Molecular Functionnuclear receptor activity
Molecular Functionnuclear steroid receptor activity
Molecular FunctionRNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular FunctionRNA polymerase II complex binding
Molecular FunctionRNA polymerase II-specific DNA-binding transcription factor binding
Molecular Functionsequence-specific DNA binding
Molecular Functionsteroid binding
Molecular Functionzinc ion binding
Biological Processcell dedifferentiation
Biological Processcell population proliferation
Biological Processembryonic placenta development
Biological Processin utero embryonic development
Biological Processinner ear development
Biological Processnegative regulation of DNA-templated transcription
Biological Processnegative regulation of stem cell differentiation
Biological Processnuclear receptor-mediated steroid hormone signaling pathway
Biological Processphotoreceptor cell maintenance
Biological Processpositive regulation of DNA-templated transcription
Biological Processpositive regulation of glycogen biosynthetic process
Biological Processpositive regulation of glycolytic process
Biological Processpositive regulation of stem cell population maintenance
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processregulation of DNA-templated transcription
Biological Processregulation of stem cell division
Biological Processregulation of transcription by RNA polymerase II
Biological Processsomatic stem cell population maintenance
Biological Processstem cell division
Biological Processstem cell population maintenance
Biological Processtrophectodermal cell proliferation
Biological Processtrophectodermal cellular morphogenesis

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Steroid hormone receptor ERR2
  • Alternative names
    • Estrogen receptor-like 2
    • Estrogen-related receptor beta
      (ERR-beta)
    • Nuclear receptor subfamily 3 group B member 2

Gene names

    • Name
      Esrrb
    • Synonyms
      Err-2, Err2, Nr3b2

Organism names

  • Taxonomic identifier
  • Strains
    • 129
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q61539
  • Secondary accessions
    • A2RTQ7
    • O09067
    • O09146
    • Q8C7A6

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Phenotypes & Variants

Disruption phenotype

Homozygote Esrrb mutant embryos die at 10.5 dpc. They have severely impaired placental formation. The mutants display abnormal chorion development associated with an overabundance of trophoblast giant cells and a severe deficiency of diploid trophoblast (PubMed:9285590).
Conditional knockdown mice exhibit head bobbing and spinning and running in circles and have hearing impairment (PubMed:17765677).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis259Loss of self-renewal in embryonic stem cells in absence of LIF. Does not interact with NCOA3.
Mutagenesis424Loss of self-renewal in embryonic stem cells in absence of LIF; when associated with A-425. Does not interact with NCOA3; when associated with A-425.
Mutagenesis425Loss of self-renewal in embryonic stem cells in absence of LIF; when associated with A-424. Does not interact with NCOA3; when associated with A-424.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 18 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00000536631-433Steroid hormone receptor ERR2

Post-translational modification

Acetylated by PCAF/KAT2 (in vitro).

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Highly expressed in undifferentiated ESCs (PubMed:23508100).
Expressed in immature horizontal cells and in rod photoreceptors at intermediate and late stages of differentiation (PubMed:20534447).
Expressed in endolymph-producing epithelial cells (PubMed:17765677).

Induction

Induced by NANOG (PubMed:23040477).
Induced by GSK3 inhibition through inhibition of TCF3 repression. Repressed by TCF3 (PubMed:23040478).
Reduced upon differentiation induced by LIF depletion (PubMed:23508100).

Developmental stage

Found in the extra-embryonic ectoderm at 5.5 dpc, 6 dpc and 6.5 dpc. At 7.5 dpc, is exclusively detected in chorion, and at 8.5 dpc is present only at its free margin. Expression is not detected in the ectoplacental cone at any stage of development, nor is placental expression detected after 8.5 dpc.

Gene expression databases

Interaction

Subunit

Binds DNA as a monomer (By similarity).
Interacts with NR0B1; represses ESRRB activity at the GATA6 promoter (PubMed:23508100, PubMed:27601327).
Interacts with NANOG; reciprocally modulates their transcriptional activities and activates POU5F1 expression (PubMed:18957414).
Interacts with NCOA3; mediates the interaction between ESRRB and RNA polymerase II complexes and allows NCOA3 corecruitment to ESRRB, KLF4, NANOG, and SOX2 enhancer regions to trigger ESRRB-dependent gene activation involved in self-renewal and pluripotency (PubMed:23019124).
Interacts with KDM1A; co-occupes the core set of ESRRB targets including ELF5 and EOMES (PubMed:26206133).
Interacts with the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12; ESRRB is probably not a core component of the integrator complex and associates to integrator via its interaction with INTS1 and INTS9; attracts the transcriptional machinery (PubMed:26206133).
Interacts with JARID2 (PubMed:26523946).
Interacts with POU5F1; recruits ESRRB near the POU5F1-SOX2 element in the NANOG proximal promoter leading to activation of NANOG expression; the interaction is DNA independent (PubMed:18662995).

Binary interactions

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region, zinc finger, domain.

TypeIDPosition(s)Description
Region1-38Disordered
Region93-211Interaction with NANOG
Zinc finger103-123NR C4-type
Zinc finger139-163NR C4-type
Region203-433Essential for ESRRB transcriptional activity and interaction with NCOA3
Domain208-432NR LBD

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    433
  • Mass (Da)
    48,328
  • Last updated
    2012-10-03 v2
  • Checksum
    1A0383E7E2ED8BF3
MSSEDRHLGSSCGSFIKTEPSSPSSGIDALSHHSPSGSSDASGGFGIALSTHANGLDSPPMFAGAGLGGNPCRKSYEDCTSGIMEDSAIKCEYMLNAIPKRLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYNCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDRVRGGRQKYKRRLDSENSPYLNLPISPPAKKPLTKIVSNLLGVEQDKLYAMPPNDIPEGDIKALTTLCELADRELVFLINWAKHIPGFPSLTLGDQMSLLQSAWMEILILGIVYRSLPYDDKLAYAEDYIMDEEHSRLVGLLDLYRAILQLVRRYKKLKVEKEEFMILKALALANSDSMYIENLEAVQKLQDLLHEALQDYELSQRHEEPRRAGKLLLTLPLLRQTAAKAVQHFYSVKLQGKVPMHKLFLEMLEAKV

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
G5E8P8G5E8P8_MOUSEEsrrb454
D3YW03D3YW03_MOUSEEsrrb378
E9QKA2E9QKA2_MOUSEEsrrb438

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict394in Ref. 1; CAA61755

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
X89594
EMBL· GenBank· DDBJ
CAA61755.1
EMBL· GenBank· DDBJ
mRNA
S82458
EMBL· GenBank· DDBJ
AAB37687.1
EMBL· GenBank· DDBJ
mRNA
AK052256
EMBL· GenBank· DDBJ
BAC34898.1
EMBL· GenBank· DDBJ
mRNA
AC126685
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AC132189
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC132595
EMBL· GenBank· DDBJ
AAI32596.2
EMBL· GenBank· DDBJ
mRNA
BC132597
EMBL· GenBank· DDBJ
AAI32598.2
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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