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Q62986

- ESR2_RAT

UniProt

Q62986 - ESR2_RAT

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Protein

Estrogen receptor beta

Gene

Esr2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi149 – 21466Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri149 – 16921NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri185 – 20925NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. core promoter sequence-specific DNA binding Source: RGD
  2. drug binding Source: RGD
  3. enzyme binding Source: RGD
  4. estrogen receptor activity Source: RGD
  5. estrogen response element binding Source: RGD
  6. hormone binding Source: RGD
  7. peroxisome proliferator activated receptor binding Source: RGD
  8. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  9. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
  10. sequence-specific DNA binding Source: RGD
  11. steroid binding Source: UniProtKB
  12. steroid hormone binding Source: RGD
  13. steroid hormone receptor activity Source: RGD
  14. zinc ion binding Source: InterPro

GO - Biological processi

  1. amygdala development Source: RGD
  2. behavioral fear response Source: RGD
  3. cellular response to drug Source: RGD
  4. cellular response to estradiol stimulus Source: RGD
  5. cellular response to magnetism Source: RGD
  6. cellular response to organic cyclic compound Source: RGD
  7. cerebellum development Source: RGD
  8. estrus Source: RGD
  9. female gonad development Source: RGD
  10. hypothalamus development Source: RGD
  11. intracellular estrogen receptor signaling pathway Source: RGD
  12. intracellular steroid hormone receptor signaling pathway Source: RGD
  13. learning or memory Source: RGD
  14. male gonad development Source: RGD
  15. negative regulation of behavior Source: RGD
  16. negative regulation of cell death Source: RGD
  17. negative regulation of epithelial cell proliferation Source: RGD
  18. negative regulation of feeding behavior Source: RGD
  19. negative regulation of neuron death Source: RGD
  20. negative regulation of reactive oxygen species metabolic process Source: RGD
  21. negative regulation of smooth muscle cell proliferation Source: RGD
  22. negative regulation of transcription from RNA polymerase II promoter Source: RGD
  23. ovarian follicle development Source: RGD
  24. positive regulation of apoptotic process Source: RGD
  25. positive regulation of epidermal growth factor receptor signaling pathway Source: RGD
  26. positive regulation of ERK1 and ERK2 cascade Source: RGD
  27. positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  28. positive regulation of transcription, DNA-templated Source: RGD
  29. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  30. prostate gland development Source: RGD
  31. regulation of neuron apoptotic process Source: RGD
  32. response to activity Source: RGD
  33. response to dexamethasone Source: RGD
  34. response to drug Source: RGD
  35. response to estradiol Source: RGD
  36. response to estrogen Source: RGD
  37. response to ethanol Source: RGD
  38. response to genistein Source: RGD
  39. response to hormone Source: RGD
  40. response to human chorionic gonadotropin Source: RGD
  41. response to insecticide Source: RGD
  42. response to nutrient levels Source: RGD
  43. response to organic cyclic compound Source: RGD
  44. response to salt Source: RGD
  45. response to testosterone Source: RGD
  46. response to water deprivation Source: RGD
  47. Sertoli cell development Source: RGD
  48. Sertoli cell proliferation Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Lipid-binding, Metal-binding, Steroid-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Estrogen receptor beta
Short name:
ER-beta
Alternative name(s):
Nuclear receptor subfamily 3 group A member 2
Gene namesi
Name:Esr2
Synonyms:Erbeta, Nr3a2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi2582. Esr2.

Subcellular locationi

GO - Cellular componenti

  1. cilium Source: RGD
  2. cytoplasm Source: RGD
  3. mitochondrion Source: MGI
  4. neuronal cell body Source: RGD
  5. neuron projection Source: RGD
  6. nucleus Source: RGD
  7. perikaryon Source: RGD
  8. perinuclear region of cytoplasm Source: RGD
  9. plasma membrane Source: RGD
  10. protein-DNA complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 530530Estrogen receptor betaPRO_0000053646Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei61 – 611Phosphoserine; alternateBy similarity
Glycosylationi61 – 611O-linked (GlcNAc); alternateBy similarity
Modified residuei87 – 871Phosphoserine; by MAPKBy similarity
Modified residuei105 – 1051Phosphoserine; by MAPKBy similarity

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ62986.
PRIDEiQ62986.

PTM databases

PhosphoSiteiQ62986.

Expressioni

Tissue specificityi

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

Gene expression databases

GenevestigatoriQ62986.

Interactioni

Subunit structurei

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.By similarity2 Publications

Protein-protein interaction databases

BioGridi247214. 5 interactions.
DIPiDIP-60383N.

Structurei

Secondary structure

1
530
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi265 – 27410
Helixi291 – 31525
Helixi319 – 3213
Helixi324 – 34724
Beta strandi353 – 3575
Beta strandi360 – 3634
Helixi364 – 3696
Helixi373 – 39018
Helixi394 – 40512
Turni406 – 4094
Helixi421 – 44323
Helixi448 – 48134
Helixi489 – 4968

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HJ1X-ray2.30A255-509[»]
1QKNX-ray2.25A255-509[»]
2J7XX-ray2.10A255-509[»]
2J7YX-ray1.80A255-509[»]
ProteinModelPortaliQ62986.
SMRiQ62986. Positions 144-216, 262-498.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ62986.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 148148ModulatingAdd
BLAST
Regioni215 – 530316Steroid-bindingAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri149 – 16921NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri185 – 20925NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG271979.
HOVERGENiHBG108344.
InParanoidiQ62986.
KOiK08551.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR028355. 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]
PfamiPF12497. ERbeta_N. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PIRSFiPIRSF500102. ER-b. 1 hit.
PIRSF002527. ER-like_NR. 1 hit.
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 2 hits.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. Align

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q62986-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MEIKNSPSSL SSPASYNCSQ SILPLEHGPI YIPSSYVDNR HEYSAMTFYS
60 70 80 90 100
PAVMNYSVPG STSNLDGGPV RLSTSPNVLW PTSGHLSPLA THCQSSLLYA
110 120 130 140 150
EPQKSPWCEA RSLEHTLPVN RETLKRKLSG SSCASPVTSP NAKRDAHFCP
160 170 180 190 200
VCSDYASGYH YGVWSCEGCK AFFKRSIQGH NDYICPATNQ CTIDKNRRKS
210 220 230 240 250
CQACRLRKCY EVGMVKCGSR RERCGYRIVR RQRSSSEQVH CLSKAKRNGG
260 270 280 290 300
HAPRVKELLL STLSPEQLVL TLLEAEPPNV LVSRPSMPFT EASMMMSLTK
310 320 330 340 350
LADKELVHMI GWAKKIPGFV ELSLLDQVRL LESCWMEVLM VGLMWRSIDH
360 370 380 390 400
PGKLIFAPDL VLDRDEGKCV EGILEIFDML LATTSRFREL KLQHKEYLCV
410 420 430 440 450
KAMILLNSSM YPLASANQEA ESSRKLTHLL NAVTDALVWV IAKSGISSQQ
460 470 480 490 500
QSVRLANLLM LLSHVRHISN KGMEHLLSMK CKNVVPVYDL LLEMLNAHTL
510 520 530
RGYKSSISGS ECSSTEDSKN KESSQNLQSQ
Length:530
Mass (Da):59,152
Last modified:July 15, 1999 - v2
Checksum:i36F269D9FD773DA9
GO
Isoform 2 (identifier: Q62986-2) [UniParc]FASTAAdd to Basket

Also known as: Beta2

The sequence of this isoform differs from the canonical sequence as follows:
     364-364: R → RSSEDPHWHVAQMKSAAPR

Show »
Length:548
Mass (Da):61,168
Checksum:iE9E636A7E317CB3B
GO
Isoform 3 (identifier: Q62986-3) [UniParc]FASTAAdd to Basket

Also known as: Beta1-delta3

The sequence of this isoform differs from the canonical sequence as follows:
     179-217: Missing.

Show »
Length:491
Mass (Da):54,663
Checksum:i6FA4105E37B02A03
GO
Isoform 4 (identifier: Q62986-4) [UniParc]FASTAAdd to Basket

Also known as: Beta2-delta3

The sequence of this isoform differs from the canonical sequence as follows:
     179-217: Missing.
     364-364: R → RSSEDPHWHVAQMKSAAPR

Show »
Length:509
Mass (Da):56,679
Checksum:iE5DA93F80B6E6BAC
GO
Isoform 5 (identifier: Q62986-5) [UniParc]FASTAAdd to Basket

Also known as: Beta1-delta4

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

Show »
Length:430
Mass (Da):47,904
Checksum:i3136E9B67BA0E01F
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti72 – 721L → Q1 PublicationCurated
Sequence conflicti72 – 721L → Q(PubMed:9492041)Curated
Sequence conflicti150 – 1501P → A1 PublicationCurated
Sequence conflicti150 – 1501P → A(PubMed:9492041)Curated
Sequence conflicti165 – 1651S → P in CAA05631. 1 PublicationCurated
Sequence conflicti505 – 5051S → P in CAA05631. 1 PublicationCurated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei179 – 21739Missing in isoform 3 and isoform 4. CuratedVSP_003697Add
BLAST
Alternative sequencei219 – 318100Missing in isoform 5. CuratedVSP_003698Add
BLAST
Alternative sequencei364 – 3641R → RSSEDPHWHVAQMKSAAPR in isoform 2 and isoform 4. 1 PublicationVSP_003699

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
PIRiJW0046.
RefSeqiNP_036886.1. NM_012754.1.
UniGeneiRn.37460.

Genome annotation databases

GeneIDi25149.
KEGGirno:25149.
UCSCiRGD:2582. rat. [Q62986-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
PIRi JW0046.
RefSeqi NP_036886.1. NM_012754.1.
UniGenei Rn.37460.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1HJ1 X-ray 2.30 A 255-509 [» ]
1QKN X-ray 2.25 A 255-509 [» ]
2J7X X-ray 2.10 A 255-509 [» ]
2J7Y X-ray 1.80 A 255-509 [» ]
ProteinModelPortali Q62986.
SMRi Q62986. Positions 144-216, 262-498.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 247214. 5 interactions.
DIPi DIP-60383N.

Chemistry

BindingDBi Q62986.
ChEMBLi CHEMBL3021.
GuidetoPHARMACOLOGYi 621.

PTM databases

PhosphoSitei Q62986.

Proteomic databases

PaxDbi Q62986.
PRIDEi Q62986.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 25149.
KEGGi rno:25149.
UCSCi RGD:2582. rat. [Q62986-1 ]

Organism-specific databases

CTDi 2100.
RGDi 2582. Esr2.

Phylogenomic databases

eggNOGi NOG271979.
HOVERGENi HBG108344.
InParanoidi Q62986.
KOi K08551.

Miscellaneous databases

EvolutionaryTracei Q62986.
NextBioi 605585.
PROi Q62986.

Gene expression databases

Genevestigatori Q62986.

Family and domain databases

Gene3Di 1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProi IPR028355. 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 ]
Pfami PF12497. ERbeta_N. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view ]
PIRSFi PIRSF500102. ER-b. 1 hit.
PIRSF002527. ER-like_NR. 1 hit.
PRINTSi PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTi SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view ]
SUPFAMi SSF48508. SSF48508. 2 hits.
PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. 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. 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.

Entry informationi

Entry nameiESR2_RAT
AccessioniPrimary (citable) accession number: Q62986
Secondary accession number(s): O35784
, O35785, O55015, O55016, O70195, Q9R185
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 15, 1999
Last modified: October 29, 2014
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3