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Q62986

- ESR2_RAT

UniProt

Q62986 - ESR2_RAT

Protein

Estrogen receptor beta

Gene

Esr2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 2 (15 Jul 1999)
      Previous versions | rss
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    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. estrogen receptor activity Source: RGD
    3. estrogen response element binding Source: RGD
    4. hormone binding Source: RGD
    5. peroxisome proliferator activated receptor binding Source: RGD
    6. protein binding Source: UniProtKB
    7. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
    8. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
    9. sequence-specific DNA binding Source: RGD
    10. steroid binding Source: UniProtKB
    11. steroid hormone receptor activity Source: RGD
    12. zinc ion binding Source: InterPro

    GO - Biological processi

    1. behavioral fear response Source: RGD
    2. cellular response to drug Source: RGD
    3. cellular response to estradiol stimulus Source: RGD
    4. cellular response to magnetism Source: RGD
    5. cellular response to organic cyclic compound Source: RGD
    6. intracellular estrogen receptor signaling pathway Source: RGD
    7. intracellular steroid hormone receptor signaling pathway Source: RGD
    8. learning or memory Source: RGD
    9. male gonad development Source: RGD
    10. negative regulation of behavior Source: RGD
    11. negative regulation of cell death Source: RGD
    12. negative regulation of epithelial cell proliferation Source: RGD
    13. negative regulation of neuron death Source: RGD
    14. negative regulation of reactive oxygen species metabolic process Source: RGD
    15. negative regulation of smooth muscle cell proliferation Source: RGD
    16. negative regulation of transcription from RNA polymerase II promoter Source: RGD
    17. positive regulation of apoptotic process Source: RGD
    18. positive regulation of epidermal growth factor receptor signaling pathway Source: RGD
    19. positive regulation of ERK1 and ERK2 cascade Source: RGD
    20. positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
    21. positive regulation of transcription, DNA-templated Source: RGD
    22. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
    23. regulation of neuron apoptotic process Source: RGD
    24. response to estradiol Source: RGD
    25. response to ethanol Source: RGD
    26. response to genistein Source: RGD
    27. response to hormone Source: RGD
    28. response to insecticide Source: RGD
    29. response to organic cyclic compound Source: RGD
    30. response to testosterone Source: RGD
    31. Sertoli cell development Source: RGD
    32. Sertoli cell proliferation Source: RGD

    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. cytoplasm Source: RGD
    2. mitochondrion Source: MGI
    3. neuronal cell body Source: RGD
    4. neuron projection Source: RGD
    5. nucleus Source: RGD
    6. perikaryon Source: RGD
    7. perinuclear region of cytoplasm Source: RGD
    8. plasma membrane Source: RGD

    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

    MEIKNSPSSL SSPASYNCSQ SILPLEHGPI YIPSSYVDNR HEYSAMTFYS    50
    PAVMNYSVPG STSNLDGGPV RLSTSPNVLW PTSGHLSPLA THCQSSLLYA 100
    EPQKSPWCEA RSLEHTLPVN RETLKRKLSG SSCASPVTSP NAKRDAHFCP 150
    VCSDYASGYH YGVWSCEGCK AFFKRSIQGH NDYICPATNQ CTIDKNRRKS 200
    CQACRLRKCY EVGMVKCGSR RERCGYRIVR RQRSSSEQVH CLSKAKRNGG 250
    HAPRVKELLL STLSPEQLVL TLLEAEPPNV LVSRPSMPFT EASMMMSLTK 300
    LADKELVHMI GWAKKIPGFV ELSLLDQVRL LESCWMEVLM VGLMWRSIDH 350
    PGKLIFAPDL VLDRDEGKCV EGILEIFDML LATTSRFREL KLQHKEYLCV 400
    KAMILLNSSM YPLASANQEA ESSRKLTHLL NAVTDALVWV IAKSGISSQQ 450
    QSVRLANLLM LLSHVRHISN KGMEHLLSMK CKNVVPVYDL LLEMLNAHTL 500
    RGYKSSISGS ECSSTEDSKN KESSQNLQSQ 530
    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 1, 2014
    This is version 143 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