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Protein

Steroid hormone receptor ERR2

Gene

Esrrb

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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:27601327, PubMed:23169531, PubMed:23508100, PubMed:26206133, PubMed:20534447, PubMed:18662995, PubMed:18957414, PubMed:27723719, PubMed:23019124). 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:26206133, PubMed:20534447, PubMed:23040478, PubMed:23040477, PubMed:23019124, PubMed:23169531). 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:23508100, PubMed:18957414). 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:23019124, PubMed:23169531, PubMed:18662995, 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:9285590, PubMed:17765677).By similarity13 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei185Important for stabilizing DNA-bindingBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi100 – 186Nuclear receptorPROSITE-ProRule annotationAdd BLAST87
Zinc fingeri103 – 123NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri139 – 163NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

  • core promoter binding Source: UniProtKB
  • enhancer binding Source: UniProtKB
  • enhancer sequence-specific DNA binding Source: UniProtKB
  • RNA polymerase II core binding Source: UniProtKB
  • RNA polymerase II distal enhancer sequence-specific DNA binding Source: BHF-UCL
  • sequence-specific DNA binding Source: UniProtKB
  • steroid binding Source: InterPro
  • steroid hormone receptor activity Source: InterPro
  • transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding Source: UniProtKB
  • transcriptional repressor activity, RNA polymerase II transcription factor binding Source: UniProtKB
  • transcription coactivator activity Source: BHF-UCL
  • transcription coactivator binding Source: UniProtKB
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • cell dedifferentiation Source: UniProtKB
  • cell proliferation Source: UniProtKB
  • embryonic placenta development Source: MGI
  • inner ear development Source: UniProtKB
  • in utero embryonic development Source: MGI
  • negative regulation of stem cell differentiation Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • photoreceptor cell maintenance Source: UniProtKB
  • positive regulation of stem cell population maintenance Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of transcription involved in G1/S transition of mitotic cell cycle Source: UniProtKB
  • positive regulation of transcription involved in G2/M transition of mitotic cell cycle Source: UniProtKB
  • regulation of stem cell division Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • stem cell division Source: UniProtKB
  • stem cell population maintenance Source: UniProtKB
  • trophectodermal cell proliferation Source: MGI
  • trophectodermal cellular morphogenesis Source: MGI

Keywordsi

Molecular functionDNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-383280. Nuclear Receptor transcription pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Steroid hormone receptor ERR2Curated
Alternative name(s):
Estrogen receptor-like 2
Estrogen-related receptor betaBy similarity
Short name:
ERR-beta
Nuclear receptor subfamily 3 group B member 2
Gene namesi
Name:EsrrbImported
Synonyms:Err-2, Err2, Nr3b2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1346832. Esrrb.

Subcellular locationi

GO - Cellular componenti

  • condensed chromosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Homozygote Esrrb mutant embryos die at E10.5. 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).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi259K → A: Loss of self-renewal in embryonic stem cells in absence of LIF. Does not interact with NCOA3. 1 Publication1
Mutagenesisi424L → A: 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. 1 Publication1
Mutagenesisi425F → A: 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. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000536631 – 433Steroid hormone receptor ERR2Add BLAST433

Post-translational modificationi

Acetylated by PCAF/KAT2 (in vitro).By similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiQ61539.
PaxDbiQ61539.
PRIDEiQ61539.

PTM databases

iPTMnetiQ61539.
PhosphoSitePlusiQ61539.

Expressioni

Tissue specificityi

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).3 Publications

Developmental stagei

Found in the extra-embryonic ectoderm at E5.5, E6 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.1 Publication

Inductioni

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).3 Publications

Gene expression databases

BgeeiENSMUSG00000021255.
CleanExiMM_ESRRB.
ExpressionAtlasiQ61539. baseline and differential.
GenevisibleiQ61539. MM.

Interactioni

Subunit structurei

Binds DNA as a monomer (By similarity). Interacts with NR0B1; represses ESRRB activity at the GATA6 promoter (PubMed:27601327, PubMed:23508100). 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 intercaction is DNA independent (PubMed:18662995).By similarity7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • RNA polymerase II core binding Source: UniProtKB
  • transcription coactivator binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi204938. 105 interactors.
DIPiDIP-46110N.
IntActiQ61539. 24 interactors.
STRINGi10090.ENSMUSP00000105833.

Structurei

3D structure databases

ProteinModelPortaliQ61539.
SMRiQ61539.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni93 – 211Interaction with NANOG1 PublicationAdd BLAST119
Regioni203 – 433Essential for ESRRB transcriptional activity and interaction with NCOA31 PublicationAdd BLAST231

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri103 – 123NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri139 – 163NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00760000118887.
HOGENOMiHOG000233467.
HOVERGENiHBG108344.
InParanoidiQ61539.
KOiK08553.

Family and domain databases

Gene3Di3.30.50.10. 1 hit.
InterProiView protein in InterPro
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR027289. Oest-rel_rcp.
IPR024178. Oest_rcpt/oest-rel_rcp.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
PfamiView protein in Pfam
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
PIRSFiPIRSF002527. ER-like_NR. 1 hit.
PIRSF500939. ERR1-2-3. 1 hit.
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiView protein in SMART
SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiView protein in PROSITE
PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Q61539-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSEDRHLGS SCGSFIKTEP SSPSSGIDAL SHHSPSGSSD ASGGFGIALS
60 70 80 90 100
THANGLDSPP MFAGAGLGGN PCRKSYEDCT SGIMEDSAIK CEYMLNAIPK
110 120 130 140 150
RLCLVCGDIA SGYHYGVASC EACKAFFKRT IQGNIEYNCP ATNECEITKR
160 170 180 190 200
RRKSCQACRF MKCLKVGMLK EGVRLDRVRG GRQKYKRRLD SENSPYLNLP
210 220 230 240 250
ISPPAKKPLT KIVSNLLGVE QDKLYAMPPN DIPEGDIKAL TTLCELADRE
260 270 280 290 300
LVFLINWAKH IPGFPSLTLG DQMSLLQSAW MEILILGIVY RSLPYDDKLA
310 320 330 340 350
YAEDYIMDEE HSRLVGLLDL YRAILQLVRR YKKLKVEKEE FMILKALALA
360 370 380 390 400
NSDSMYIENL EAVQKLQDLL HEALQDYELS QRHEEPRRAG KLLLTLPLLR
410 420 430
QTAAKAVQHF YSVKLQGKVP MHKLFLEMLE AKV
Length:433
Mass (Da):48,328
Last modified:October 3, 2012 - v2
Checksum:i1A0383E7E2ED8BF3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti394L → W in CAA61755 (PubMed:8652414).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X89594 mRNA. Translation: CAA61755.1.
S82458 mRNA. Translation: AAB37687.1.
AK052256 mRNA. Translation: BAC34898.1.
AC126685 Genomic DNA. No translation available.
AC132189 Genomic DNA. No translation available.
BC132595 mRNA. Translation: AAI32596.2.
BC132597 mRNA. Translation: AAI32598.2.
PIRiS58087.
RefSeqiNP_001152972.1. NM_001159500.1.
NP_036064.3. NM_011934.4.
UniGeneiMm.235550.

Genome annotation databases

EnsembliENSMUST00000021680; ENSMUSP00000021680; ENSMUSG00000021255.
ENSMUST00000167891; ENSMUSP00000131335; ENSMUSG00000021255.
GeneIDi26380.
KEGGimmu:26380.
UCSCiuc007ohw.2. mouse.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiERR2_MOUSE
AccessioniPrimary (citable) accession number: Q61539
Secondary accession number(s): A2RTQ7
, O09067, O09146, Q8C7A6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: October 3, 2012
Last modified: July 5, 2017
This is version 147 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families