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Reviewed, UniProtKB/Swiss-Prot Q92731 (ESR2_HUMAN)

Last modified June 16, 2009. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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: ESTRB, NR3A2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length530 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.

Subunit structure

Binds DNA as a homodimer. Can form a heterodimer with ESR1. Interacts with NCOA3, NCOA5 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with PELP1 and UBE1C. Isoform beta-2/cx preferentially forms a hetereodimer with ESR1 rather than ESR2 and inhibits DNA-binding by ESR1. Interacts with AKAP13. Interacts with DNTTIP2. Interacts with isoform 4 of TXNRD1. Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19

Subcellular location

Nucleus.

Tissue specificity

Isoform beta-1 is expressed in testis and ovary, and at a lower level in heart, brain, placenta, liver, skeletal muscle, spleen, thymus, prostate, colon, bone marrow, mammary gland and uterus. Also found in uterine bone, breast, and ovarian tumor cell lines, but not in colon and liver tumors. Isoform beta-2 is expressed in spleen, thymus, testis and ovary and at a lower level in skeletal muscle, prostate, colon, small intestine, leukocytes, bone marrow, mammary gland and uterus. Isoform beta-3 is found in testis. Isoform beta-4 is expressed in testis, and at a lower level in spleen, thymus, ovary, mammary gland and uterus. Isoform beta-5 is expressed in testis, placenta, skeletal muscle, spleen and leukocytes, and at a lower level in heart, lung, liver, kidney, pancreas, thymus, prostate, colon, small intestine, bone marrow, mammary gland and uterus. Not expressed in brain.

Domain

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

Sequence similarities

Belongs to the nuclear hormone receptor family. NR3 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PPP5CP530414EBI-78505,EBI-716663
PRMT2P553451EBI-78505,EBI-78458

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q92731-1)

Also known as: Beta-1;

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: Q92731-2)

Also known as: Beta-2; CX;

The sequence of this isoform differs from the canonical sequence as follows:
     469-530: SNKGMEHLLN...KEGSQNPQSQ → RAEKASQTLTSFGMKMETLLPEATMEQ
Isoform 3 (identifier: Q92731-3)

Also known as: Beta-2A;

The sequence of this isoform differs from the canonical sequence as follows:
     319-323: FVELS → MRGNA
     324-530: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 4 (identifier: Q92731-4)

Also known as: Beta-3;

The sequence of this isoform differs from the canonical sequence as follows:
     469-530: SNKGMEHLLN...KEGSQNPQSQ → SSLSLSWRLF...SFEACQQPRE
Isoform 5 (identifier: Q92731-5)

Also known as: Beta-4;

The sequence of this isoform differs from the canonical sequence as follows:
     469-530: SNKGMEHLLNMKCKNVVPVYDLLLEMLNAHVLRGCKSSITGSECSPAEDSKSKEGSQNPQSQ → RWGEKQFIHLKLS
Note: Does not form homodimers.
Isoform 6 (identifier: Q92731-6)

Also known as: Beta-5;

The sequence of this isoform differs from the canonical sequence as follows:
     469-530: SNKGMEHLLNMKCKNVVPVYDLLLEMLNAHVLRGCKSSITGSECSPAEDSKSKEGSQNPQSQ → RYAP
Note: Does not form homodimers.
Isoform 7 (identifier: Q92731-7)

Also known as: Beta-5A;

The sequence of this isoform differs from the canonical sequence as follows:
     319-409: Missing.
Isoform 8 (identifier: Q92731-8)

Also known as: Beta-6;

The sequence of this isoform differs from the canonical sequence as follows:
     365-375: DEGKCVEGILE → YVPSGHSDPGC
     376-530: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 530530Estrogen receptor beta
PRO_0000053642

Regions

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

Amino acid modifications

Modified residue871Phosphoserine By similarity
Modified residue4881Phosphotyrosine By similarity

Natural variations

Alternative sequence319 – 40991Missing in isoform 7.
VSP_003685
Alternative sequence319 – 3235FVELS → MRGNA in isoform 3.
VSP_003684
Alternative sequence324 – 530207Missing in isoform 3.
VSP_003686
Alternative sequence365 – 37511DEGKCVEGILE → YVPSGHSDPGC in isoform 8.
VSP_003687
Alternative sequence376 – 530155Missing in isoform 8.
VSP_003688
Alternative sequence469 – 53062SNKGM…NPQSQ → RAEKASQTLTSFGMKMETLL PEATMEQ in isoform 2.
VSP_003689
Alternative sequence469 – 53062SNKGM…NPQSQ → SSLSLSWRLFMLREASCHGV RQTPGGAHMSVSRSRSFEAC QQPRE in isoform 4.
VSP_003690
Alternative sequence469 – 53062SNKGM…NPQSQ → RWGEKQFIHLKLS in isoform 5.
VSP_003691
Alternative sequence469 – 53062SNKGM…NPQSQ → RYAP in isoform 6.
VSP_003692

Secondary structure

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

Details...

Sequences

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

Last modified July 15, 1999. Version 2.
Checksum: 8CAE34215992418A

FASTA53059,216
        10         20         30         40         50         60 
MDIKNSPSSL NSPSSYNCSQ SILPLEHGSI YIPSSYVDSH HEYPAMTFYS PAVMNYSIPS 

        70         80         90        100        110        120 
NVTNLEGGPG RQTTSPNVLW PTPGHLSPLV VHRQLSHLYA EPQKSPWCEA RSLEHTLPVN 

       130        140        150        160        170        180 
RETLKRKVSG NRCASPVTGP GSKRDAHFCA VCSDYASGYH YGVWSCEGCK AFFKRSIQGH 

       190        200        210        220        230        240 
NDYICPATNQ CTIDKNRRKS CQACRLRKCY EVGMVKCGSR RERCGYRLVR RQRSADEQLH 

       250        260        270        280        290        300 
CAGKAKRSGG HAPRVRELLL DALSPEQLVL TLLEAEPPHV LISRPSAPFT EASMMMSLTK 

       310        320        330        340        350        360 
LADKELVHMI SWAKKIPGFV ELSLFDQVRL LESCWMEVLM MGLMWRSIDH PGKLIFAPDL 

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

       430        440        450        460        470        480 
DSSRKLAHLL NAVTDALVWV IAKSGISSQQ QSMRLANLLM LLSHVRHASN KGMEHLLNMK 

       490        500        510        520        530 
CKNVVPVYDL LLEMLNAHVL RGCKSSITGS ECSPAEDSKS KEGSQNPQSQ 

« Hide

Isoform 2 (Beta-2) (CX).

Checksum: F068DBC63DC838A6
Show »

FASTA49555,483
Isoform 3 (Beta-2A).

Checksum: 158D376C56D3CA12
Show »

FASTA32335,944
Isoform 4 (Beta-3).

Checksum: EE88C42CBB24775E
Show »

FASTA51357,518
Isoform 5 (Beta-4).

Checksum: 9B6017FE950720F0
Show »

FASTA48154,096
Isoform 6 (Beta-5).

Checksum: 673B0DB5FAF03C26
Show »

FASTA47252,959
Isoform 7 (Beta-5A).

Checksum: 35B686E3C0D32D0F
Show »

FASTA43948,614
Isoform 8 (Beta-6).

Checksum: E2FA83EE3C519EE5
Show »

FASTA37541,948

References

« Hide 'large scale' references
[1]"The complete primary structure of human estrogen receptor beta (hERbeta) and its heterodimerization with ER alpha in vivo and in vitro."
Ogawa S., Inoue S., Watanabe T., Hiroi H., Orimo A., Hosoi T., Ouchi Y., Muramatsu M.
Biochem. Biophys. Res. Commun. 243:122-126(1998) [PubMed: 9473491] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Cloning and characterization of human estrogen receptor beta isoforms."
Moore J.T., McKee D.D., Slentz-Kesler K., Moore L.B., Jones S.A., Horne E.L., Su J.-L., Kliewer S.A., Lehmann J.M., Willson T.M.
Biochem. Biophys. Res. Commun. 247:75-78(1998) [PubMed: 9636657] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 4), NUCLEOTIDE SEQUENCE [MRNA] OF 409-482 (ISOFORM 5), NUCLEOTIDE SEQUENCE [MRNA] OF 409-472 (ISOFORM 6).
Tissue: Mammary gland and Testis.
[3]"Estrogen receptor-beta mRNA variants in human and murine tissues."
Lu B., Leygue E., Dotzlaw H., Murphy L.J., Murphy L.C., Watson P.H.
Mol. Cell. Endocrinol. 138:199-203(1998) [PubMed: 9685228] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Tissue: Ovary.
[4]"Molecular cloning and characterization of human estrogen receptor beta cx: a potential inhibitor of estrogen action in human."
Ogawa S., Inoue S., Watanabe T., Orimo A., Hosoi T., Ouchi Y., Muramatsu M.
Nucleic Acids Res. 26:3505-3512(1998) [PubMed: 9671811] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CHARACTERIZATION.
Tissue: Testis.
[5]"Estrogen receptor (ER)-beta isoforms: a key to understanding ER-beta signaling."
Leung Y.K., Mak P., Hassan S., Ho S.M.
Proc. Natl. Acad. Sci. U.S.A. 103:13162-13167(2006) [PubMed: 16938840] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 6).
Tissue: Prostate.
[6]SeattleSNPs variation discovery resource
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Testis.
[8]"Cloning and characterization of human estrogen receptor beta promoter."
Li L.C., Yeh C.C., Nojima D., Dahiya R.
Biochem. Biophys. Res. Commun. 275:682-689(2000) [PubMed: 10964723] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-69.
[9]"ER beta: identification and characterization of a novel human estrogen receptor."
Mosselman S., Polman J., Dijkema R.
FEBS Lett. 392:49-53(1996) [PubMed: 8769313] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 49-530 (ISOFORM 1), CHARACTERIZATION.
Tissue: Testis.
[10]Brandenberger A.W., Lebovic D., Taylor R.N., Jaffe R.B.
Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 59-530 (ISOFORMS 7 AND 8).
Tissue: Endometrium.
[11]"Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300."
Chen H., Lin R.J., Schiltz R.L., Chakravarti D., Nash A., Nagy L., Privalsky M.L., Nakatani Y., Evans R.M.
Cell 90:569-580(1997) [PubMed: 9267036] [Abstract]
Cited for: INTERACTION WITH NCOA3.
[12]"Human estrogen receptor beta binds DNA in a manner similar to and dimerizes with estrogen receptor alpha."
Pace P., Taylor J., Suntharalingam S., Coombes R.C., Ali S.
J. Biol. Chem. 272:25832-25838(1997) [PubMed: 9325313] [Abstract]
Cited for: CHARACTERIZATION.
[13]"Cloning and characterization of RAP250, a nuclear receptor coactivator."
Caira F., Antonson P., Pelto-Huikko M., Treuter E., Gustafsson J.-A.
J. Biol. Chem. 275:5308-5317(2000) [PubMed: 10681503] [Abstract]
Cited for: INTERACTION WITH NCOA6.
[14]"CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant."
Sauve F., McBroom L.D.B., Gallant J., Moraitis A.N., Labrie F., Giguere V.
Mol. Cell. Biol. 21:343-353(2001) [PubMed: 11113208] [Abstract]
Cited for: INTERACTION WITH NCOA5.
[15]"The proto-oncoprotein Brx activates estrogen receptor beta by a p38 mitogen-activated protein kinase pathway."
Driggers P.H., Segars J.H., Rubino D.M.
J. Biol. Chem. 276:46792-46797(2001) [PubMed: 11579095] [Abstract]
Cited for: INTERACTION WITH AKAP13.
[16]"Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade."
Wong C.-W., McNally C., Nickbarg E., Komm B.S., Cheskis B.J.
Proc. Natl. Acad. Sci. U.S.A. 99:14783-14788(2002) [PubMed: 12415108] [Abstract]
Cited for: INTERACTION WITH PELP1.
[17]"ERBP, a novel estrogen receptor binding protein enhancing the activity of estrogen receptor."
Bu H., Kashireddy P., Chang J., Zhu Y.T., Zhang Z., Zheng W., Rao S.M., Zhu Y.-J.
Biochem. Biophys. Res. Commun. 317:54-59(2004) [PubMed: 15047147] [Abstract]
Cited for: INTERACTION WITH DNTTIP2.
[18]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004) [PubMed: 14759258] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[19]"An alternative splicing variant of the selenoprotein thioredoxin reductase is a modulator of estrogen signaling."
Damdimopoulos A.E., Miranda-Vizuete A., Treuter E., Gustafsson J.-A., Spyrou G.
J. Biol. Chem. 279:38721-38729(2004) [PubMed: 15199063] [Abstract]
Cited for: INTERACTION WITH TXNRD1.
+Additional computationally mapped references.

Cross-references

Sequence databases

AB006590 mRNA. Translation: BAA24953.1.
AF051427 mRNA. Translation: AAC05985.1.
AF051428 mRNA. Translation: AAC05751.1.
AF061054 mRNA. Translation: AAC39784.1.
AF061055 mRNA. Translation: AAC39785.1.
AF060555 mRNA. Translation: AAC15234.1.
AF124790 mRNA. Translation: AAD32580.1.
AF047463 mRNA. Translation: AAC03786.1.
AB006589 mRNA. Translation: BAA31966.1.
DQ838582 mRNA. Translation: ABH09189.1.
DQ838583 mRNA. Translation: ABH09190.1.
AY785359 Genomic DNA. Translation: AAV31779.1.
BC024181 mRNA. Translation: AAH24181.1.
AF191544 Genomic DNA. No translation available.
X99101 mRNA. Translation: CAA67555.1. Different initiation.
AF074598 mRNA. Translation: AAC25602.1.
AF074599 mRNA. Translation: AAC25603.1.
IPIIPI00023212.
IPI00218153.
IPI00218155.
IPI00218156.
IPI00218157.
IPI00218158.
IPI00218159.
IPI00397583.
PIRJC5939.
PW0044.
S71400.
RefSeqNP_001035365.1.
NP_001035366.1.
NP_001428.1.
UniGeneHs.525392
Hs.660607

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1L2JX-ray2.95A/B256-505[»]
1NDEX-ray3.00A256-501[»]
1QKMX-ray1.80A255-509[»]
1U3QX-ray2.40A/B/C/D261-500[»]
1U3RX-ray2.21A/B261-501[»]
1U3SX-ray2.50A/B261-500[»]
1U9EX-ray2.40A/B261-501[»]
1X76X-ray2.20A/B261-500[»]
1X78X-ray2.30A/B261-500[»]
1X7BX-ray2.30A/B261-500[»]
1X7JX-ray2.30A/B261-500[»]
1YY4X-ray2.70A/B263-530[»]
1YYEX-ray2.03A/B263-530[»]
1ZAFX-ray2.20A/B263-500[»]
2FSZX-ray2.20A/B257-502[»]
2GIUX-ray2.20A260-500[»]
2I0GX-ray2.50A/B256-505[»]
2JJ3X-ray2.28A/B256-505[»]
2NV7X-ray2.10A/B263-500[»]
2QTUX-ray2.53A/B256-505[»]
2Z4BX-ray2.34A/B256-505[»]
SMRQ92731. Positions 144-216.
DisProtDP00079.
ModBaseSearch...

Protein-protein interaction databases

IntActQ92731. 2 interactions.

PTM databases

PhosphoSiteQ92731.

Proteomic databases

PRIDEQ92731.

Genome annotation databases

EnsemblENSG00000140009. Homo sapiens. [Contig view]
GeneID2100.
KEGGhsa:2100.

Organism-specific databases

GeneCardsGC14M063763.
H-InvDBHIX0011730.
HGNCHGNC:3468. ESR2.
MIM601663. gene.
PharmGKBPA27886.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ92731.
OMAQ92731. WCEARSL.

Enzyme and pathway databases

Pathway_Interaction_DBer_nongenomic_pathway. Plasma membrane estrogen receptor signaling.

Gene expression databases

ArrayExpressQ92731.
BgeeQ92731.
GermOnlineENSG00000140009. Homo sapiens.

Family and domain databases

InterProIPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR000324. VitD_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
Gene3DG3DSA:1.10.565.10. Nucl_hrmn_rcpt_lig_bd. 1 hit.
G3DSA:3.30.50.10. Znf_NHR/GATA. 1 hit.
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
PR00350. VITAMINDR.
ProDomPD000035. Znf_C4steroid. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB01128. Bicalutamide.
DB00783. Estradiol.
DB01196. Estramustine.
DB00481. Raloxifene.
DB00675. Tamoxifen.
DB01108. Trilostane.
NextBio8495.
PMAP-CutDBQ92731.
SOURCESearch...

Entry information

Entry nameESR2_HUMAN
AccessionPrimary (citable) accession number: Q92731
Secondary accession number(s): O60608 expand/collapse secondary AC list , O60685, O60702, O60703, O75583, O75584, Q0MWT5, Q0MWT6, Q86Z31, Q9UEV6, Q9UHD3, Q9UQK9
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 15, 1999
Last modified: June 16, 2009
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 14

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

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents