Q61539 · ERR2_MOUSE
- ProteinSteroid hormone receptor ERR2
- GeneEsrrb
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids433 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
DNA binding | 100-186 | Nuclear receptor | ||||
Sequence: KRLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYNCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDRVRGGRQKYK | ||||||
Site | 185 | Important for stabilizing DNA-binding | ||||
Sequence: Y |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSteroid hormone receptor ERR2
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ61539
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
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).
Conditional knockdown mice exhibit head bobbing and spinning and running in circles and have hearing impairment (PubMed:17765677).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 259 | Loss of self-renewal in embryonic stem cells in absence of LIF. Does not interact with NCOA3. | ||||
Sequence: K → A | ||||||
Mutagenesis | 424 | Loss 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. | ||||
Sequence: L → A | ||||||
Mutagenesis | 425 | Loss 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. | ||||
Sequence: F → A |
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.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000053663 | 1-433 | Steroid hormone receptor ERR2 | |||
Sequence: MSSEDRHLGSSCGSFIKTEPSSPSSGIDALSHHSPSGSSDASGGFGIALSTHANGLDSPPMFAGAGLGGNPCRKSYEDCTSGIMEDSAIKCEYMLNAIPKRLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYNCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDRVRGGRQKYKRRLDSENSPYLNLPISPPAKKPLTKIVSNLLGVEQDKLYAMPPNDIPEGDIKALTTLCELADRELVFLINWAKHIPGFPSLTLGDQMSLLQSAWMEILILGIVYRSLPYDDKLAYAEDYIMDEEHSRLVGLLDLYRAILQLVRRYKKLKVEKEEFMILKALALANSDSMYIENLEAVQKLQDLLHEALQDYELSQRHEEPRRAGKLLLTLPLLRQTAAKAVQHFYSVKLQGKVPMHKLFLEMLEAKV |
Post-translational modification
Acetylated by PCAF/KAT2 (in vitro).
Keywords
- PTM
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).
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).
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).
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
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | Q61539 | HIF1A Q16665 | 2 | EBI-2312731, EBI-447269 | |
BINARY | Q61539 | Mta2 Q9R190 | 3 | EBI-2312731, EBI-904134 | |
BINARY | Q61539 | Nr0b1 Q61066 | 3 | EBI-2312731, EBI-2312665 | |
BINARY | Q61539 | Tfcp2l1 Q3UNW5 | 4 | EBI-2312731, EBI-5691372 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, zinc finger, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-38 | Disordered | ||||
Sequence: MSSEDRHLGSSCGSFIKTEPSSPSSGIDALSHHSPSGS | ||||||
Region | 93-211 | Interaction with NANOG | ||||
Sequence: YMLNAIPKRLCLVCGDIASGYHYGVASCEACKAFFKRTIQGNIEYNCPATNECEITKRRRKSCQACRFMKCLKVGMLKEGVRLDRVRGGRQKYKRRLDSENSPYLNLPISPPAKKPLTK | ||||||
Zinc finger | 103-123 | NR C4-type | ||||
Sequence: CLVCGDIASGYHYGVASCEAC | ||||||
Zinc finger | 139-163 | NR C4-type | ||||
Sequence: CPATNECEITKRRRKSCQACRFMKC | ||||||
Region | 203-433 | Essential for ESRRB transcriptional activity and interaction with NCOA3 | ||||
Sequence: PPAKKPLTKIVSNLLGVEQDKLYAMPPNDIPEGDIKALTTLCELADRELVFLINWAKHIPGFPSLTLGDQMSLLQSAWMEILILGIVYRSLPYDDKLAYAEDYIMDEEHSRLVGLLDLYRAILQLVRRYKKLKVEKEEFMILKALALANSDSMYIENLEAVQKLQDLLHEALQDYELSQRHEEPRRAGKLLLTLPLLRQTAAKAVQHFYSVKLQGKVPMHKLFLEMLEAKV | ||||||
Domain | 208-432 | NR LBD | ||||
Sequence: PLTKIVSNLLGVEQDKLYAMPPNDIPEGDIKALTTLCELADRELVFLINWAKHIPGFPSLTLGDQMSLLQSAWMEILILGIVYRSLPYDDKLAYAEDYIMDEEHSRLVGLLDLYRAILQLVRRYKKLKVEKEEFMILKALALANSDSMYIENLEAVQKLQDLLHEALQDYELSQRHEEPRRAGKLLLTLPLLRQTAAKAVQHFYSVKLQGKVPMHKLFLEMLEAK |
Sequence similarities
Belongs to the nuclear hormone receptor family. NR3 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length433
- Mass (Da)48,328
- Last updated2012-10-03 v2
- Checksum1A0383E7E2ED8BF3
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 394 | in Ref. 1; CAA61755 | ||||
Sequence: L → W |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |