Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q62986 (ESR2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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:
Estrogen receptor beta

Short name=ER-beta
Alternative name(s):
Nuclear receptor subfamily 3 group A member 2
Gene names
Name:Esr2
Synonyms:Erbeta, Nr3a2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length530 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds estrogens with an affinity similar to that of ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform 3 and isoform 4 are unable to bind DNA and activate transcription due to the truncation of the DNA binding domain. Isoform 2 shows loss of ligand binding affinity and suppresses ER-alpha and ER-beta1 mediated transcriptional activation and may act as a dominant negative regulator of estrogen action.

Subunit structure

Binds DNA as a homodimer. Can form a heterodimer with ESR1. Interacts with NCOA1, NCOA3, NCOA5 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with PELP1, UBE1C and AKAP13. Interacts with DNTTIP2 By similarity. Interacts with CCDC62 in the presence of estradiol/E2; this interaction seems to enhance the transcription of target genes. Interacts with PRMT2 By similarity. Interacts with DYX1C1. Ref.6 Ref.7

Subcellular location

Nucleus.

Tissue specificity

Expressed in prostate, ovary, lung, liver, kidney, fat, bone, brain, uterus and testis.

Domain

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Post-translational modification

Phosphorylation at Ser-87 and Ser-105 recruits NCOA1 By similarity.

Sequence similarities

Belongs to the nuclear hormone receptor family. NR3 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Sequence caution

The sequence CAA05631.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DomainZinc-finger
   LigandDNA-binding
Lipid-binding
Metal-binding
Steroid-binding
Zinc
   Molecular functionReceptor
   PTMGlycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSertoli cell development

Inferred from expression pattern PubMed 24056172. Source: RGD

Sertoli cell proliferation

Inferred from mutant phenotype PubMed 17928626. Source: RGD

behavioral fear response

Inferred from direct assay PubMed 15514081. Source: RGD

cellular response to drug

Inferred from expression pattern PubMed 19279558. Source: RGD

cellular response to estradiol stimulus

Inferred from expression pattern PubMed 17928626. Source: RGD

cellular response to magnetism

Inferred from expression pattern PubMed 23469792. Source: RGD

cellular response to organic cyclic compound

Inferred from expression pattern PubMed 23596885. Source: RGD

intracellular estrogen receptor signaling pathway

Traceable author statement Ref.2. Source: RGD

intracellular steroid hormone receptor signaling pathway

Inferred from direct assay PubMed 17928626. Source: RGD

learning or memory

Inferred from mutant phenotype PubMed 16904920. Source: RGD

male gonad development

Inferred from expression pattern PubMed 23620208. Source: RGD

negative regulation of behavior

Inferred from direct assay PubMed 15514081. Source: RGD

negative regulation of cell death

Inferred from mutant phenotype PubMed 21127968. Source: RGD

negative regulation of epithelial cell proliferation

Inferred from direct assay PubMed 12370428. Source: RGD

negative regulation of neuron death

Inferred from direct assay PubMed 15126114. Source: RGD

negative regulation of reactive oxygen species metabolic process

Inferred from mutant phenotype PubMed 23608653. Source: RGD

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.2. Source: RGD

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay PubMed 17928626. Source: RGD

positive regulation of epidermal growth factor receptor signaling pathway

Inferred from mutant phenotype PubMed 17928626. Source: RGD

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15564578. Source: RGD

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 15564578. Source: RGD

regulation of neuron apoptotic process

Inferred from direct assay PubMed 15126114. Source: RGD

response to estradiol

Inferred from expression pattern PubMed 19948032. Source: RGD

response to ethanol

Inferred from expression pattern PubMed 23591044. Source: RGD

response to genistein

Inferred from expression pattern PubMed 19230619. Source: RGD

response to hormone

Inferred from expression pattern PubMed 23591044. Source: RGD

response to insecticide

Inferred from expression pattern PubMed 23943137. Source: RGD

response to organic cyclic compound

Inferred from expression pattern PubMed 24070737. Source: RGD

response to testosterone

Inferred from mutant phenotype PubMed 16904920. Source: RGD

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 16122717. Source: RGD

mitochondrion

Inferred from direct assay PubMed 15024130. Source: MGI

neuron projection

Inferred from direct assay PubMed 16122717. Source: RGD

neuronal cell body

Inferred from direct assay PubMed 23701910. Source: RGD

nucleus

Inferred from direct assay PubMed 16122717PubMed 17928626. Source: RGD

perikaryon

Inferred from direct assay PubMed 16122717. Source: RGD

perinuclear region of cytoplasm

Inferred from direct assay PubMed 17928626. Source: RGD

plasma membrane

Inferred from direct assay PubMed 17928626PubMed 18489713. Source: RGD

   Molecular_functioncore promoter sequence-specific DNA binding

Inferred from direct assay PubMed 24046281. Source: RGD

estrogen receptor activity

Inferred from direct assay PubMed 15105439. Source: RGD

estrogen response element binding

Inferred from direct assay Ref.2. Source: RGD

hormone binding

Inferred from direct assay PubMed 17928626. Source: RGD

sequence-specific DNA binding

Inferred from direct assay PubMed 12200235. Source: RGD

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

steroid binding

Inferred from direct assay PubMed 15705806. Source: UniProtKB

steroid hormone receptor activity

Inferred from direct assay PubMed 17928626. Source: RGD

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q62986-1)

Also known as: Beta1;

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: Q62986-2)

Also known as: Beta2;

The sequence of this isoform differs from the canonical sequence as follows:
     364-364: R → RSSEDPHWHVAQMKSAAPR
Isoform 3 (identifier: Q62986-3)

Also known as: Beta1-delta3;

The sequence of this isoform differs from the canonical sequence as follows:
     179-217: Missing.
Isoform 4 (identifier: Q62986-4)

Also known as: Beta2-delta3;

The sequence of this isoform differs from the canonical sequence as follows:
     179-217: Missing.
     364-364: R → RSSEDPHWHVAQMKSAAPR
Isoform 5 (identifier: Q62986-5)

Also known as: Beta1-delta4;

The sequence of this isoform differs from the canonical sequence as follows:
     219-318: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 530530Estrogen receptor beta
PRO_0000053646

Regions

DNA binding149 – 21466Nuclear receptor
Zinc finger149 – 16921NR C4-type
Zinc finger185 – 20925NR C4-type
Region1 – 148148Modulating
Region215 – 530316Steroid-binding

Amino acid modifications

Modified residue611Phosphoserine; alternate By similarity
Modified residue871Phosphoserine; by MAPK By similarity
Modified residue1051Phosphoserine; by MAPK By similarity
Glycosylation611O-linked (GlcNAc); alternate By similarity

Natural variations

Alternative sequence179 – 21739Missing in isoform 3 and isoform 4.
VSP_003697
Alternative sequence219 – 318100Missing in isoform 5.
VSP_003698
Alternative sequence3641R → RSSEDPHWHVAQMKSAAPR in isoform 2 and isoform 4.
VSP_003699

Experimental info

Sequence conflict721L → Q Ref.3
Sequence conflict721L → Q Ref.4
Sequence conflict1501P → A Ref.3
Sequence conflict1501P → A Ref.4
Sequence conflict1651S → P in CAA05631. Ref.3
Sequence conflict5051S → P in CAA05631. Ref.3

Secondary structure

......................... 530
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Beta1) [UniParc].

Last modified July 15, 1999. Version 2.
Checksum: 36F269D9FD773DA9

FASTA53059,152
        10         20         30         40         50         60 
MEIKNSPSSL SSPASYNCSQ SILPLEHGPI YIPSSYVDNR HEYSAMTFYS PAVMNYSVPG 

        70         80         90        100        110        120 
STSNLDGGPV RLSTSPNVLW PTSGHLSPLA THCQSSLLYA EPQKSPWCEA RSLEHTLPVN 

       130        140        150        160        170        180 
RETLKRKLSG SSCASPVTSP NAKRDAHFCP VCSDYASGYH YGVWSCEGCK AFFKRSIQGH 

       190        200        210        220        230        240 
NDYICPATNQ CTIDKNRRKS CQACRLRKCY EVGMVKCGSR RERCGYRIVR RQRSSSEQVH 

       250        260        270        280        290        300 
CLSKAKRNGG HAPRVKELLL STLSPEQLVL TLLEAEPPNV LVSRPSMPFT EASMMMSLTK 

       310        320        330        340        350        360 
LADKELVHMI GWAKKIPGFV ELSLLDQVRL LESCWMEVLM VGLMWRSIDH PGKLIFAPDL 

       370        380        390        400        410        420 
VLDRDEGKCV EGILEIFDML LATTSRFREL KLQHKEYLCV KAMILLNSSM YPLASANQEA 

       430        440        450        460        470        480 
ESSRKLTHLL NAVTDALVWV IAKSGISSQQ QSVRLANLLM LLSHVRHISN KGMEHLLSMK 

       490        500        510        520        530 
CKNVVPVYDL LLEMLNAHTL RGYKSSISGS ECSSTEDSKN KESSQNLQSQ 

« Hide

Isoform 2 (Beta2) [UniParc].

Checksum: E9E636A7E317CB3B
Show »

FASTA54861,168
Isoform 3 (Beta1-delta3) [UniParc].

Checksum: 6FA4105E37B02A03
Show »

FASTA49154,663
Isoform 4 (Beta2-delta3) [UniParc].

Checksum: E5DA93F80B6E6BAC
Show »

FASTA50956,679
Isoform 5 (Beta1-delta4) [UniParc].

Checksum: 3136E9B67BA0E01F
Show »

FASTA43047,904

References

[1]"Cloning of a novel receptor expressed in rat prostate and ovary."
Kuiper G.G.J.M., Enmark E., Pelto-Huikko M., Nilsson S., Gustafsson J.-A.
Proc. Natl. Acad. Sci. U.S.A. 93:5925-5930(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 46-530 (ISOFORM 1).
Strain: Sprague-Dawley.
Tissue: Prostate.
[2]"A novel isoform of rat estrogen receptor beta with 18 amino acid insertion in the ligand binding domain as a putative dominant negative regular of estrogen action."
Maruyama K., Endoh H., Sasaki-Iwaoka H., Kanou H., Shimaya E., Hashimoto S., Kato S., Kawashima H.
Biochem. Biophys. Res. Commun. 246:142-147(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 46-530 (ISOFORM 2).
Strain: Wistar.
Tissue: Ovary.
[3]"Tissue specific responses to estrogen: an explanation based on differential activation of multiple estrogen receptors with different estrogen response elements."
Aldridge T.C.
Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 2).
Strain: Wistar.
Tissue: Prostate.
[4]"Identification of estrogen receptor beta2, a functional variant of estrogen receptor beta expressed in normal rat tissues."
Petersen D.N., Tkalcevic G.T., Koza-Taylor P.H., Turi T.G., Brown T.A.
Endocrinology 139:1082-1092(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 46-530 (ISOFORMS 1; 3 AND 4).
Strain: Sprague-Dawley.
[5]"A novel splice variant of estrogen receptor beta found in rat brain."
Price R., Handa R.J.
Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases
Cited for: PARTIAL NUCLEOTIDE SEQUENCE (ISOFORM 5).
Strain: Sprague-Dawley.
Tissue: Brain.
[6]"The activating enzyme of NEDD8 inhibits steroid receptor function."
Fan M., Long X., Bailey J.A., Reed C.A., Osborne E., Gize E.A., Kirk E.A., Bigsby R.M., Nephew K.P.
Mol. Endocrinol. 16:315-330(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBE1C.
[7]"Functional interaction of DYX1C1 with estrogen receptors suggests involvement of hormonal pathways in dyslexia."
Massinen S., Tammimies K., Tapia-Paez I., Matsson H., Hokkanen M.E., Soederberg O., Landegren U., Castren E., Gustafsson J.A., Treuter E., Kere J.
Hum. Mol. Genet. 18:2802-2812(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DYX1C1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U57439 mRNA. Translation: AAC52602.1.
AB012721 mRNA. Translation: BAA25431.1.
AJ002602 Genomic DNA. Translation: CAA05631.1. Different initiation.
AJ002603 Genomic DNA. Translation: CAA05632.1.
AF042058 mRNA. Translation: AAB97424.1.
AF042059 mRNA. Translation: AAB97425.1.
AF042060 mRNA. Translation: AAB97426.1.
AF042061 mRNA. Translation: AAB97427.1.
AF161187 mRNA. Translation: AAD47637.1.
PIRJW0046.
RefSeqNP_036886.1. NM_012754.1.
UniGeneRn.37460.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HJ1X-ray2.30A255-509[»]
1QKNX-ray2.25A255-509[»]
2J7XX-ray2.10A255-509[»]
2J7YX-ray1.80A255-509[»]
ProteinModelPortalQ62986.
SMRQ62986. Positions 144-216, 262-498.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid247214. 5 interactions.
DIPDIP-60383N.

Chemistry

BindingDBQ62986.
ChEMBLCHEMBL3021.
GuidetoPHARMACOLOGY621.

PTM databases

PhosphoSiteQ62986.

Proteomic databases

PaxDbQ62986.
PRIDEQ62986.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25149.
KEGGrno:25149.
UCSCRGD:2582. rat. [Q62986-1]

Organism-specific databases

CTD2100.
RGD2582. Esr2.

Phylogenomic databases

eggNOGNOG271979.
HOVERGENHBG108344.
InParanoidQ62986.
KOK08551.

Gene expression databases

GenevestigatorQ62986.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProIPR028355. ER-beta/gamma.
IPR021064. Estrogen_rcpt_beta_N.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR024178. Oest_rcpt/oest-rel_rcp.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF12497. ERbeta_N. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PIRSFPIRSF500102. ER-b. 1 hit.
PIRSF002527. ER-like_NR. 1 hit.
PRINTSPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 2 hits.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ62986.
NextBio605585.
PROQ62986.

Entry information

Entry nameESR2_RAT
AccessionPrimary (citable) accession number: Q62986
Secondary accession number(s): O35784 expand/collapse secondary AC list , O35785, O55015, O55016, O70195, Q9R185
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 15, 1999
Last modified: April 16, 2014
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references