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O95718 (ERR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Steroid hormone receptor ERR2
Alternative name(s):
ERR beta-2
Estrogen receptor-like 2
Estrogen-related receptor beta
Short name=ERR-beta
Nuclear receptor subfamily 3 group B member 2
Gene names
Name:ESRRB
Synonyms:ERRB2, ESRL2, NR3B2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length508 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Nuclear receptor, may regulate ESR1 transcriptional activity. Induces the expression of PERM1 in the skeletal muscle. Ref.7 Ref.8

Subunit structure

Binds DNA as a monomer. Ref.9

Subcellular location

Nucleus Ref.10.

Post-translational modification

Acetylated by PCAF/KAT2 (in vitro). Ref.11

Involvement in disease

Deafness, autosomal recessive, 35 (DFNB35) [MIM:608565]: A form of non-syndromic deafness characterized by non-progressive, prelingual hearing loss.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

Sequence similarities

Belongs to the nuclear hormone receptor family. NR3 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DiseaseDeafness
Disease mutation
Non-syndromic deafness
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionReceptor
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processgene expression

Traceable author statement. Source: Reactome

intracellular receptor signaling pathway

Traceable author statement PubMed 9344655. Source: GOC

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of transcription, DNA-templated

Inferred from direct assay Ref.8. Source: UniProtKB

stem cell maintenance

Inferred from electronic annotation. Source: Ensembl

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

trophectodermal cell proliferation

Inferred from electronic annotation. Source: Ensembl

trophectodermal cellular morphogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentnucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from sequence or structural similarity. Source: BHF-UCL

   Molecular_functionRNA polymerase II distal enhancer sequence-specific DNA binding

Inferred from sequence or structural similarity. Source: BHF-UCL

ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity

Traceable author statement PubMed 9344655. Source: ProtInc

sequence-specific DNA binding

Inferred from direct assay Ref.9. Source: UniProtKB

steroid binding

Inferred from electronic annotation. Source: InterPro

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

transcription coactivator activity

Inferred from sequence or structural similarity. Source: BHF-UCL

transcription factor binding

Inferred from sequence or structural similarity. Source: BHF-UCL

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95718-1)

Also known as: ERRbeta2-delta10;

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.
Isoform 2 (identifier: O95718-2)

The sequence of this isoform differs from the canonical sequence as follows:
     433-508: VGQEQLRGSP...GQGKHLWLTM → AWARADSLQE...PQRAGWPRAA
Isoform 3 (identifier: O95718-3)

Also known as: ERRbeta-short-form;

The sequence of this isoform differs from the canonical sequence as follows:
     434-508: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 508508Steroid hormone receptor ERR2
PRO_0000053662

Regions

DNA binding100 – 18687Nuclear receptor Ref.9
Zinc finger103 – 12321NR C4-type
Zinc finger139 – 16325NR C4-type

Sites

Site1851Important for stabilizing DNA-binding

Natural variations

Alternative sequence433 – 50876VGQEQ…LWLTM → AWARADSLQEWRPLEQVPSP LHRATKRQHVHFLTPLPPPP SVAWVGTAQAGYHLEVFLPQ RAGWPRAA in isoform 2.
VSP_042211
Alternative sequence434 – 50875Missing in isoform 3.
VSP_042212
Natural variant1101A → V in DFNB35. Ref.12
VAR_043503
Natural variant3201L → P in DFNB35. Ref.12
VAR_043504
Natural variant3421V → L in DFNB35. Ref.12
VAR_043505
Natural variant3471L → P in DFNB35. Ref.12
VAR_043506
Natural variant3861P → S. Ref.12
Corresponds to variant rs61742642 [ dbSNP | Ensembl ].
VAR_043507
Natural variant3891T → M in DFNB35; uncertain pathological significance. Ref.12
VAR_043508

Experimental info

Mutagenesis1851Y → A: 6-fold decrease in DNA-binding affinity. Ref.9
Sequence conflict2481D → E in BAH02305. Ref.3
Sequence conflict4291L → V in AAI31518. Ref.6

Secondary structure

............. 508
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (ERRbeta2-delta10) [UniParc].

Last modified January 25, 2012. Version 2.
Checksum: 1BF4637DC1D45B13

FASTA50856,208
        10         20         30         40         50         60 
MSSDDRHLGS SCGSFIKTEP SSPSSGIDAL SHHSPSGSSD ASGGFGLALG THANGLDSPP 

        70         80         90        100        110        120 
MFAGAGLGGT PCRKSYEDCA SGIMEDSAIK CEYMLNAIPK RLCLVCGDIA SGYHYGVASC 

       130        140        150        160        170        180 
EACKAFFKRT IQGNIEYSCP ATNECEITKR RRKSCQACRF MKCLKVGMLK EGVRLDRVRG 

       190        200        210        220        230        240 
GRQKYKRRLD SESSPYLSLQ ISPPAKKPLT KIVSYLLVAE PDKLYAMPPP GMPEGDIKAL 

       250        260        270        280        290        300 
TTLCDLADRE LVVIIGWAKH IPGFSSLSLG DQMSLLQSAW MEILILGIVY RSLPYDDKLV 

       310        320        330        340        350        360 
YAEDYIMDEE HSRLAGLLEL YRAILQLVRR YKKLKVEKEE FVTLKALALA NSDSMYIEDL 

       370        380        390        400        410        420 
EAVQKLQDLL HEALQDYELS QRHEEPWRTG KLLLTLPLLR QTAAKAVQHF YSVKLQGKVP 

       430        440        450        460        470        480 
MHKLFLEMLE AKVGQEQLRG SPKDERMSSH DGKCPFQSAA FTSRDQSNSP GIPNPRPSSP 

       490        500 
TPLNERGRQI SPSTRTPGGQ GKHLWLTM 

« Hide

Isoform 2 [UniParc].

Checksum: C219C84D914DF1C6
Show »

FASTA50055,619
Isoform 3 (ERRbeta-short-form) [UniParc].

Checksum: ED1D3F87E2798DD1
Show »

FASTA43348,054

References

« Hide 'large scale' references
[1]"Identification of two hERR2-related novel nuclear receptors utilizing bioinformatics and inverse PCR."
Chen F., Zhang Q., McDonald T., Davidoff M.J., Bailey W., Bai C., Liu Q., Caskey C.T.
Gene 228:101-109(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Testis.
[2]"Identification and characterization of two novel splicing isoforms of human estrogen-related receptor beta."
Zhou W., Liu Z., Wu J., Liu J.H., Hyder S.M., Antoniou E., Lubahn D.B.
J. Clin. Endocrinol. Metab. 91:569-579(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), ALTERNATIVE SPLICING.
Tissue: Heart and Testis.
[3]"Comprehensive DNA-binding analysis of human hormone nuclear receptors by fluorescence correlation spectroscopy based on cell-free system."
Kobayashi T., Kodani Y., Sawasaki T., Endo Y.
Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[4]"Isolation of cDNA coding for multiple human nuclear receptor clones."
Kaighin V.A., Martin A.L., Aronstam R.S.
Submitted (DEC-2010) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[5]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-503 (ISOFORM 1).
[7]"Modulation of ER alpha transcriptional activity by the orphan nuclear receptor ERR beta and evidence for differential effects of long- and short-form splice variants."
Bombail V., Collins F., Brown P., Saunders P.T.
Mol. Cell. Endocrinol. 314:53-61(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ALTERNATIVE SPLICING.
[8]"Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1)- and estrogen-related receptor (ERR)-induced regulator in muscle 1 (Perm1) is a tissue-specific regulator of oxidative capacity in skeletal muscle cells."
Cho Y., Hazen B.C., Russell A.P., Kralli A.
J. Biol. Chem. 288:25207-25218(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Monomeric complex of human orphan estrogen related receptor-2 with DNA: a pseudo-dimer interface mediates extended half-site recognition."
Gearhart M.D., Holmbeck S.M., Evans R.M., Dyson H.J., Wright P.E.
J. Mol. Biol. 327:819-832(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 97-194, SUBUNIT, DNA-BINDING, MUTAGENESIS OF TYR-185.
[10]"Estrogen receptor related beta is expressed in human endometrium throughout the normal menstrual cycle."
Bombail V., MacPherson S., Critchley H.O., Saunders P.T.
Hum. Reprod. 23:2782-2790(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[11]"An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha."
Wilson B.J., Tremblay A.M., Deblois G., Sylvain-Drolet G., Giguere V.
Mol. Endocrinol. 24:1349-1358(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION BY PCAF/KAT2B.
[12]"Mutations of ESRRB encoding estrogen-related receptor beta cause autosomal-recessive nonsyndromic hearing impairment DFNB35."
Collin R.W.J., Kalay E., Tariq M., Peters T., van der Zwaag B., Venselaar H., Oostrik J., Lee K., Ahmed Z.M., Caylan R., Li Y., Spierenburg H.A., Eyupoglu E., Heister A., Riazuddin S., Bahat E., Ansar M., Arslan S. expand/collapse author list , Wollnik B., Brunner H.G., Cremers C.W.R.J., Karaguzel A., Ahmad W., Cremers F.P.M., Vriend G., Friedman T.B., Riazuddin S., Leal S.M., Kremer H.
Am. J. Hum. Genet. 82:125-138(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS DFNB35 VAL-110; PRO-320; LEU-342; PRO-347 AND MET-389, VARIANT SER-386.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS9850.2. [O95718-1]
RefSeqNP_004443.3. NM_004452.3. [O95718-1]
XP_006720141.1. XM_006720078.1. [O95718-3]
UniGeneHs.435845.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LO1NMR-A97-192[»]
ProteinModelPortalO95718.
SMRO95718. Positions 95-433.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000261532.

Chemistry

BindingDBO95718.
ChEMBLCHEMBL3751.
GuidetoPHARMACOLOGY623.

PTM databases

PhosphoSiteO95718.

Proteomic databases

MaxQBO95718.
PaxDbO95718.
PRIDEO95718.

Protocols and materials databases

DNASU2103.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261532; ENSP00000261532; ENSG00000119715. [O95718-2]
ENST00000380887; ENSP00000370270; ENSG00000119715. [O95718-1]
ENST00000505752; ENSP00000423004; ENSG00000119715. [O95718-2]
ENST00000509242; ENSP00000422488; ENSG00000119715. [O95718-1]
ENST00000556177; ENSP00000451658; ENSG00000119715. [O95718-3]
GeneID2103.
KEGGhsa:2103.
UCSCuc001xsq.1. human. [O95718-1]

Organism-specific databases

CTD2103.
GeneCardsGC14P076837.
GeneReviewsESRRB.
HGNCHGNC:3473. ESRRB.
MIM602167. gene.
608565. phenotype.
neXtProtNX_O95718.
Orphanet90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
PharmGKBPA27889.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG282629.
HOGENOMHOG000233467.
HOVERGENHBG108344.
KOK08553.
OMASYEDCAG.
TreeFamTF323751.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.
SignaLinkO95718.

Gene expression databases

ArrayExpressO95718.
BgeeO95718.
CleanExHS_ESRRB.
GenevestigatorO95718.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProIPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR027289. Oest-rel_rcp.
IPR024178. Oest_rcpt/oest-rel_rcp.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PIRSFPIRSF002527. ER-like_NR. 1 hit.
PIRSF500939. ERR1-2-3. 1 hit.
PRINTSPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSESRRB. human.
EvolutionaryTraceO95718.
GeneWikiEstrogen-related_receptor_beta.
GenomeRNAi2103.
NextBio8507.
PROO95718.
SOURCESearch...

Entry information

Entry nameERR2_HUMAN
AccessionPrimary (citable) accession number: O95718
Secondary accession number(s): A2VDJ2 expand/collapse secondary AC list , B6ZGU4, Q5F0P7, Q5F0P8, Q9HCB4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: January 25, 2012
Last modified: July 9, 2014
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM