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UniProtKB - O95718 (ERR2_HUMAN)

Protein

Steroid hormone receptor ERR2

Gene

ESRRB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Isoform 3: 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 transcription activity (PubMed:17920186, PubMed:19755138). 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. 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. Also regulates expression of multiple rod-specific genes and is required for survival of this cell type (By similarity). Plays a role as transcription factor activator of GATA6, NR0B1, POU5F1 and PERM1 (PubMed:23836911). Plays a role as transcription factor repressor of NFE2L2 transcriptional activity and ESR1 transcriptional activity (PubMed:17920186, PubMed:19755138). 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. Can coassemble on structured DNA elements with other transcription factors like SOX2, POU5F1, KDM1A and NCOA3 to trigger ESRRB-dependent gene activation. 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. Also plays a role inner ear development by controlling expression of ion channels and transporters and in early placentation (By similarity).By similarity3 Publications
Isoform 1: 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 transcription activity. Positively regulates ESR1 transcriptional activity upon E2 stimulation.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei185Important for stabilizing DNA-binding1

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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-383280 Nuclear Receptor transcription pathway
SignaLinkiO95718
SIGNORiO95718

Names & Taxonomyi

Protein namesi
Recommended name:
Steroid hormone receptor ERR2Curated
Alternative name(s):
ERR beta-2
Estrogen receptor-like 2
Estrogen-related receptor beta1 Publication
Short name:
ERR-beta
Nuclear receptor subfamily 3 group B member 2
Gene namesi
Name:ESRRBImported
Synonyms:ERRB2, ESRL2, NR3B2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000119715.14
HGNCiHGNC:3473 ESRRB
MIMi602167 gene
neXtProtiNX_O95718

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Deafness, autosomal recessive, 35 (DFNB35)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of non-syndromic deafness characterized by non-progressive, prelingual hearing loss.
See also OMIM:608565
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043503110A → V in DFNB35. 1 PublicationCorresponds to variant dbSNP:rs121909110EnsemblClinVar.1
Natural variantiVAR_043504320L → P in DFNB35. 1 Publication1
Natural variantiVAR_043505342V → L in DFNB35. 1 PublicationCorresponds to variant dbSNP:rs121909111EnsemblClinVar.1
Natural variantiVAR_043506347L → P in DFNB35. 1 Publication1
Natural variantiVAR_043508389T → M in DFNB35; uncertain pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201714970EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi185Y → A: 6-fold decrease in DNA-binding affinity. 1 Publication1

Keywords - Diseasei

Deafness, Disease mutation, Non-syndromic deafness

Organism-specific databases

DisGeNETi2103
GeneReviewsiESRRB
MalaCardsiESRRB
MIMi608565 phenotype
OpenTargetsiENSG00000119715
Orphaneti90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
PharmGKBiPA27889

Chemistry databases

ChEMBLiCHEMBL3751
GuidetoPHARMACOLOGYi623

Polymorphism and mutation databases

BioMutaiESRRB

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000536621 – 433Steroid hormone receptor ERR2Add BLAST433

Post-translational modificationi

Acetylated by PCAF/KAT2 (in vitro).1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

EPDiO95718
PaxDbiO95718
PeptideAtlasiO95718
PRIDEiO95718
ProteomicsDBi51011
51012 [O95718-2]
51013 [O95718-3]

PTM databases

iPTMnetiO95718
PhosphoSitePlusiO95718

Expressioni

Gene expression databases

BgeeiENSG00000119715 Expressed in 82 organ(s), highest expression level in cortex of kidney
CleanExiHS_ESRRB
ExpressionAtlasiO95718 baseline and differential
GenevisibleiO95718 HS

Interactioni

Subunit structurei

Binds DNA as a monomer (PubMed:12654265). Interacts with NR0B1; represses ESRRB activity at the GATA6 promoter. Interacts with NANOG; reciprocally modulates their transcriptional activities and activates POU5F1 expression. 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. Interacts with KDM1A; co-occupes the core set of ESRRB targets including ELF5 and EOMES. 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. Interacts with JARID2. 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 (By similarity). Interacts with NFE2L2; represses NFE2L2 transcriptional activity (PubMed:17920186). Isoform 1 interacts with ESR1 (PubMed:19755138).By similarity3 Publications

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi108406, 92 interactors
IntActiO95718, 3 interactors
STRINGi9606.ENSP00000370270

Structurei

Secondary structure

1433
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO95718
SMRiO95718
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95718

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini208 – 432NR LBDPROSITE-ProRule annotationAdd BLAST225

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni93 – 211Interaction with NANOGBy similarityAdd BLAST119
Regioni203 – 433Essential for ESRRB transcriptional activity and interaction with NCOA3By similarityAdd BLAST231

Sequence similaritiesi

Belongs to the nuclear hormone receptor family. NR3 subfamily.Curated

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
InParanoidiO95718
KOiK08553
OMAiDCASAIM
OrthoDBiEOG091G0DYP
TreeFamiTF323751

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
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
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 3 (identifier: O95718-3) [UniParc]FASTAAdd to basket
Also known as: ERRbeta-short-form1 Publication

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSSDDRHLGS SCGSFIKTEP SSPSSGIDAL SHHSPSGSSD ASGGFGLALG 
        60         70         80         90        100
THANGLDSPP MFAGAGLGGT PCRKSYEDCA SGIMEDSAIK CEYMLNAIPK 
       110        120        130        140        150
RLCLVCGDIA SGYHYGVASC EACKAFFKRT IQGNIEYSCP ATNECEITKR 
       160        170        180        190        200
RRKSCQACRF MKCLKVGMLK EGVRLDRVRG GRQKYKRRLD SESSPYLSLQ 
       210        220        230        240        250
ISPPAKKPLT KIVSYLLVAE PDKLYAMPPP GMPEGDIKAL TTLCDLADRE 
       260        270        280        290        300
LVVIIGWAKH IPGFSSLSLG DQMSLLQSAW MEILILGIVY RSLPYDDKLV 
       310        320        330        340        350
YAEDYIMDEE HSRLAGLLEL YRAILQLVRR YKKLKVEKEE FVTLKALALA 
       360        370        380        390        400
NSDSMYIEDL EAVQKLQDLL HEALQDYELS QRHEEPWRTG KLLLTLPLLR 
       410        420        430 
QTAAKAVQHF YSVKLQGKVP MHKLFLEMLE AKV
Length:433
Mass (Da):48,054
Last modified:June 7, 2017 - v3
Checksum:iED1D3F87E2798DD1
GO
Isoform 1 (identifier: O95718-1) [UniParc]FASTAAdd to basket
Also known as: ERRbeta2-delta101 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     433-433: V → VGQEQLRGSP...GQGKHLWLTM

Note: Primate-specific splicing isoform.1 Publication
Show »
Length:508
Mass (Da):56,208
Checksum:i1BF4637DC1D45B13
GO
Isoform 2 (identifier: O95718-2) [UniParc]FASTAAdd to basket
Also known as: ERRbeta21 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     433-433: V → AWARADSLQEWRPLEQVPSPLHRATKRQHVHFLTPLPPPPSVAWVGTAQAGYHLEVFLPQRAGWPRAA

Note: Primate-specific splicing isoform.1 Publication
Show »
Length:500
Mass (Da):55,619
Checksum:iC219C84D914DF1C6
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7EWD9E7EWD9_HUMAN
Steroid hormone receptor ERR2
ESRRB
438Annotation score:
A0A2R8Y491A0A2R8Y491_HUMAN
Steroid hormone receptor ERR2
ESRRB
454Annotation score:
A0A2R8Y509A0A2R8Y509_HUMAN
Steroid hormone receptor ERR2
ESRRB
99Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti248D → E in BAH02305 (Ref. 3) Curated1
Sequence conflicti429L → V in AAI31518 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043503110A → V in DFNB35. 1 PublicationCorresponds to variant dbSNP:rs121909110EnsemblClinVar.1
Natural variantiVAR_043504320L → P in DFNB35. 1 Publication1
Natural variantiVAR_043505342V → L in DFNB35. 1 PublicationCorresponds to variant dbSNP:rs121909111EnsemblClinVar.1
Natural variantiVAR_043506347L → P in DFNB35. 1 Publication1
Natural variantiVAR_043507386P → S1 PublicationCorresponds to variant dbSNP:rs61742642EnsemblClinVar.1
Natural variantiVAR_043508389T → M in DFNB35; uncertain pathological significance. 1 PublicationCorresponds to variant dbSNP:rs201714970EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_058967433V → VGQEQLRGSPKDERMSSHDG KCPFQSAAFTSRDQSNSPGI PNPRPSSPTPLNERGRQISP STRTPGGQGKHLWLTM in isoform 1. 1
Alternative sequenceiVSP_058968433V → AWARADSLQEWRPLEQVPSP LHRATKRQHVHFLTPLPPPP SVAWVGTAQAGYHLEVFLPQ RAGWPRAA in isoform 2. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF094517 mRNA Translation: AAC99409.1
AY451389 mRNA Translation: AAS15571.1
AY451390 mRNA Translation: AAS15572.1
AB307714 mRNA Translation: BAH02305.1
HQ692852 mRNA Translation: ADZ17363.1
AC008050 Genomic DNA Translation: AAG17472.1
AC016543 Genomic DNA No translation available.
BC131517 mRNA Translation: AAI31518.1
CCDSiCCDS9850.2 [O95718-1]
RefSeqiNP_004443.3, NM_004452.3 [O95718-1]
XP_016876575.1, XM_017021086.1
UniGeneiHs.435845

Genome annotation databases

EnsembliENST00000380887; ENSP00000370270; ENSG00000119715 [O95718-1]
ENST00000505752; ENSP00000423004; ENSG00000119715 [O95718-2]
ENST00000509242; ENSP00000422488; ENSG00000119715 [O95718-1]
GeneIDi2103
KEGGihsa:2103
UCSCiuc001xsq.2 human [O95718-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF094517 mRNA Translation: AAC99409.1
AY451389 mRNA Translation: AAS15571.1
AY451390 mRNA Translation: AAS15572.1
AB307714 mRNA Translation: BAH02305.1
HQ692852 mRNA Translation: ADZ17363.1
AC008050 Genomic DNA Translation: AAG17472.1
AC016543 Genomic DNA No translation available.
BC131517 mRNA Translation: AAI31518.1
CCDSiCCDS9850.2 [O95718-1]
RefSeqiNP_004443.3, NM_004452.3 [O95718-1]
XP_016876575.1, XM_017021086.1
UniGeneiHs.435845

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LO1NMR-A97-192[»]
ProteinModelPortaliO95718
SMRiO95718
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108406, 92 interactors
IntActiO95718, 3 interactors
STRINGi9606.ENSP00000370270

Chemistry databases

ChEMBLiCHEMBL3751
GuidetoPHARMACOLOGYi623

PTM databases

iPTMnetiO95718
PhosphoSitePlusiO95718

Polymorphism and mutation databases

BioMutaiESRRB

Proteomic databases

EPDiO95718
PaxDbiO95718
PeptideAtlasiO95718
PRIDEiO95718
ProteomicsDBi51011
51012 [O95718-2]
51013 [O95718-3]

Protocols and materials databases

DNASUi2103
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000380887; ENSP00000370270; ENSG00000119715 [O95718-1]
ENST00000505752; ENSP00000423004; ENSG00000119715 [O95718-2]
ENST00000509242; ENSP00000422488; ENSG00000119715 [O95718-1]
GeneIDi2103
KEGGihsa:2103
UCSCiuc001xsq.2 human [O95718-3]

Organism-specific databases

CTDi2103
DisGeNETi2103
EuPathDBiHostDB:ENSG00000119715.14
GeneCardsiESRRB
GeneReviewsiESRRB
HGNCiHGNC:3473 ESRRB
MalaCardsiESRRB
MIMi602167 gene
608565 phenotype
neXtProtiNX_O95718
OpenTargetsiENSG00000119715
Orphaneti90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
PharmGKBiPA27889
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00760000118887
HOGENOMiHOG000233467
HOVERGENiHBG108344
InParanoidiO95718
KOiK08553
OMAiDCASAIM
OrthoDBiEOG091G0DYP
TreeFamiTF323751

Enzyme and pathway databases

ReactomeiR-HSA-383280 Nuclear Receptor transcription pathway
SignaLinkiO95718
SIGNORiO95718

Miscellaneous databases

ChiTaRSiESRRB human
EvolutionaryTraceiO95718
GeneWikiiEstrogen-related_receptor_beta
GenomeRNAii2103
PROiPR:O95718
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000119715 Expressed in 82 organ(s), highest expression level in cortex of kidney
CleanExiHS_ESRRB
ExpressionAtlasiO95718 baseline and differential
GenevisibleiO95718 HS

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
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
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiERR2_HUMAN
AccessioniPrimary (citable) accession number: O95718
Secondary accession number(s): A2VDJ2
, B6ZGU4, Q5F0P7, Q5F0P8, Q9HCB4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: June 7, 2017
Last modified: November 7, 2018
This is version 186 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
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