Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P06211

- ESR1_RAT

UniProt

P06211 - ESR1_RAT

Protein

Estrogen receptor

Gene

Esr1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 162 (01 Oct 2014)
      Sequence version 1 (01 Jan 1988)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 By similarity.By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi190 – 25566Nuclear receptorPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri190 – 21021NR C4-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri226 – 25025NR C4-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. core promoter sequence-specific DNA binding Source: RGD
    2. DNA binding Source: RGD
    3. enzyme binding Source: RGD
    4. estrogen receptor activity Source: RGD
    5. hormone binding Source: RGD
    6. protein binding Source: UniProtKB
    7. protein complex binding Source: RGD
    8. sequence-specific DNA binding transcription factor activity Source: InterPro
    9. steroid binding Source: UniProtKB
    10. steroid hormone receptor activity Source: RGD
    11. type 1 metabotropic glutamate receptor binding Source: RGD
    12. zinc ion binding Source: InterPro

    GO - Biological processi

    1. baculum development Source: RGD
    2. cellular response to estradiol stimulus Source: UniProtKB
    3. decidualization Source: RGD
    4. intracellular steroid hormone receptor signaling pathway Source: UniProtKB
    5. male gonad development Source: RGD
    6. negative regulation of glucose import Source: RGD
    7. negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
    8. negative regulation of neuron death Source: RGD
    9. negative regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
    10. negative regulation of smooth muscle cell proliferation Source: RGD
    11. negative regulation of triglyceride metabolic process Source: RGD
    12. osteoblast development Source: RGD
    13. phospholipase C-activating G-protein coupled receptor signaling pathway Source: UniProtKB
    14. positive regulation of cytosolic calcium ion concentration Source: UniProtKB
    15. positive regulation of epidermal growth factor receptor signaling pathway Source: RGD
    16. positive regulation of ERK1 and ERK2 cascade Source: RGD
    17. positive regulation of nitric oxide biosynthetic process Source: UniProtKB
    18. positive regulation of nitric-oxide synthase activity Source: UniProtKB
    19. positive regulation of phospholipase C activity Source: UniProtKB
    20. positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
    21. positive regulation of transcription from RNA polymerase II promoter Source: RGD
    22. regulation of neuron apoptotic process Source: RGD
    23. response to estradiol Source: RGD
    24. Sertoli cell development Source: RGD
    25. Sertoli cell proliferation Source: RGD
    26. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, 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
    Short name:
    ER
    Alternative name(s):
    ER-alpha
    Estradiol receptor
    Nuclear receptor subfamily 3 group A member 1
    Gene namesi
    Name:Esr1
    Synonyms:Esr, Estr, Nr3a1
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi2581. Esr1.

    Subcellular locationi

    Nucleus PROSITE-ProRule annotation. Cytoplasm By similarity. Golgi apparatus By similarity. Cell membrane By similarity
    Note: Colocalizes with ZDHHC7 and ZDHHC21 in the Golgi apparatus where most probably palmitoylation occurs. Associated with the plasma membrane when palmitoylated.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: RGD
    2. Golgi apparatus Source: UniProtKB-SubCell
    3. mitochondrion Source: RGD
    4. neuron projection Source: RGD
    5. nucleus Source: UniProtKB
    6. perikaryon Source: RGD
    7. perinuclear region of cytoplasm Source: RGD
    8. plasma membrane Source: RGD
    9. protein complex Source: RGD
    10. terminal bouton Source: RGD
    11. T-tubule Source: RGD

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Golgi apparatus, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 600600Estrogen receptorPRO_0000053623Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi10 – 101O-linked (GlcNAc)By similarity
    Modified residuei109 – 1091Phosphoserine; by CDK2By similarity
    Modified residuei111 – 1111Phosphoserine; by CDK2By similarity
    Modified residuei123 – 1231PhosphoserineBy similarity
    Modified residuei172 – 1721Phosphoserine; by CK2By similarity
    Modified residuei265 – 2651Asymmetric dimethylarginine; by PRMT1By similarity
    Lipidationi452 – 4521S-palmitoyl cysteineBy similarity
    Modified residuei542 – 5421Phosphotyrosine; by Tyr-kinasesBy similarity
    Glycosylationi576 – 5761O-linked (GlcNAc)By similarity

    Post-translational modificationi

    Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably enhances transcriptional activity. Dephosphorylation at Ser-123 by PPP5C inhibits its transactivation activity By similarity.By similarity
    Ubiquitinated. Deubiquitinated by OTUB1 By similarity.By similarity
    Dimethylated by PRMT1 at Arg-265. The methylation may favor cytoplasmic localization By similarity.By similarity
    Palmitoylated at Cys-452 by ZDHHC7 and ZDHHC21. This modification is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation, but not for signaling mediated by the nuclear hormone receptor By similarity.By similarity

    Keywords - PTMi

    Glycoprotein, Lipoprotein, Methylation, Palmitate, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiP06211.
    PRIDEiP06211.

    PTM databases

    PhosphoSiteiP06211.

    Expressioni

    Gene expression databases

    GenevestigatoriP06211.

    Interactioni

    Subunit structurei

    Binds DNA as a homodimer By similarity. Can form a heterodimer with ESR2 By similarity. Interacts with coactivator NCOA5. Interacts with NCOA7; the interaction is ligand-inducible. Interacts with AKAP13, CUEDC2, HEXIM1, KDM5A, MAP1S, PELP1, SMARD1, and UBE1C. Interacts with MUC1; the interaction is stimulated by 7 beta-estradiol (E2) and enhances ERS1-mediated transcription. Interacts with DNTTIP2, and UIMC1. Interacts with KMT2D/MLL2. Interacts with ATAD2; the interaction is enhanced by estradiol. Interacts with KIF18A and LDB1. Interacts with RLIM (via its C-terminus). Interacts with MACROD1. Interacts with SH2D4A and PLCG. Interacts with SH2D4A; the interaction blocks binding to PLCG and inhibits estrogen-induced cell proliferation. Interacts with DYNLL1. Interacts with CCDC62; the interaction requires estradiol and appears to enhance the transcription of target genes. Interacts with NR2C1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth. Interacts with DYX1C1. Interacts with PRMT2. Interacts with PI3KR1 or PIK3R2, SRC and PTK2/FAK1. Interacts with RBFOX2. Interacts with EP300; the interaction is estrogen-dependent and enhanced by CITED1. Interacts with CITED1; the interaction is estrogen-dependent By similarity. Interacts with FAM120B, FOXL2, PHB2 and SLC30A9. Interacts with coactivators NCOA3 and NCOA6. Interacts with STK3/MST2 only in the presence of SAV1 and vice-versa. Binds to CSNK1D. Interacts with NCOA2; NCOA2 can interact with ESE1 AF-1 and AF-2 domains simultaneously and mediate their transcriptional synergy. Interacts with DDX5. Interacts with NCOA1; the interaction seems to require a self-association of N-terminal and C-terminal regions. Interacts with ZNF366, DDX17, NFKB1, RELA, SP1 and SP3. Interacts with NRIP1 By similarity. Interacts with GPER1; the interaction occurs in an estrogen-dependent manner By similarity.By similarity

    Protein-protein interaction databases

    BioGridi247000. 9 interactions.
    DIPiDIP-41279N.
    IntActiP06211. 2 interactions.
    MINTiMINT-234578.
    STRINGi10116.ENSRNOP00000026350.

    Structurei

    3D structure databases

    ProteinModelPortaliP06211.
    SMRiP06211. Positions 185-258, 306-555.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 189189Modulating (transactivation AF-1); mediates interaction with MACROD1By similarityAdd
    BLAST
    Regioni35 – 179145Interaction with DDX5; self-associationBy similarityAdd
    BLAST
    Regioni35 – 4713Required for interaction with NCOA1By similarityAdd
    BLAST
    Regioni190 – 315126Mediates interaction with DNTTIP2By similarityAdd
    BLAST
    Regioni256 – 31560HingeAdd
    BLAST
    Regioni267 – 600334Interaction with AKAP13By similarityAdd
    BLAST
    Regioni269 – 600332Self-associationBy similarityAdd
    BLAST
    Regioni316 – 600285Transactivation AF-2By similarityAdd
    BLAST
    Regioni316 – 556241Steroid-bindingAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi64 – 718Poly-Ala
    Compositional biasi171 – 1744Poly-Ser

    Domaini

    Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The modulating domain, also known as A/B or AF-1 domain has a ligand-independent transactivation function. The C-terminus contains a ligand-dependent transactivation domain, also known as E/F or AF-2 domain which overlaps with the ligand binding domain. AF-1 and AF-2 activate transcription independently and synergistically and act in a promoter- and cell-specific manner By similarity.By similarity

    Sequence similaritiesi

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

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri190 – 21021NR C4-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri226 – 25025NR C4-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG320746.
    HOGENOMiHOG000233468.
    HOVERGENiHBG108344.
    InParanoidiP06211.
    KOiK08550.
    PhylomeDBiP06211.

    Family and domain databases

    Gene3Di1.10.565.10. 2 hits.
    3.30.50.10. 1 hit.
    InterProiIPR008946. Nucl_hormone_rcpt_ligand-bd.
    IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
    IPR024178. Oest_rcpt/oest-rel_rcp.
    IPR001292. Oestr_rcpt.
    IPR024736. Oestrogen-typ_rcpt_final_C_dom.
    IPR001723. Str_hrmn_rcpt.
    IPR001628. Znf_hrmn_rcpt.
    IPR013088. Znf_NHR/GATA.
    [Graphical view]
    PfamiPF12743. ESR1_C. 1 hit.
    PF00104. Hormone_recep. 1 hit.
    PF02159. Oest_recep. 1 hit.
    PF00105. zf-C4. 1 hit.
    [Graphical view]
    PIRSFiPIRSF500101. ER-a. 1 hit.
    PIRSF002527. ER-like_NR. 1 hit.
    PRINTSiPR00543. OESTROGENR.
    PR00398. 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]

    Sequencei

    Sequence statusi: Complete.

    P06211-1 [UniParc]FASTAAdd to Basket

    « Hide

    MTMTLHTKAS GMALLHQIQG NELEPLNRPQ LKMPMERALG EVYVDNSKPA    50
    VFNYPEGAAY EFNAAAAAAA AGASAPVYGQ SSITYGPGSE AAAFGANSLG 100
    AFPQLNSVSP SPLMLLHPPP HVSPFLHPHG HQVPYYLENE PSAYAVRDTG 150
    PPAFYRSNSD NRRQNGRERL SSSSEKGNMI MESAKETRYC AVCNDYASGY 200
    HYGVWSCEGC KAFFKRSIQG HNDYMCPATN QCTIDKNRRK SCQACRLRKC 250
    YEVGMMKGGI RKDRRGGRML KHKRQRDDLE GRNEMGTSGD MRAANLWPSP 300
    LVIKHTKKNS PALSLTADQM VSALLDAEPP LIYSEYDPSR PFSEASMMGL 350
    LTNLADRELV HMINWAKRVP GFGDLNLHDQ VHLLECAWLE ILMIGLVWRS 400
    MEHPGKLLFA PNLLLDRNQG KCVEGMVEIF DMLLATSSRF RMMNLQGEEF 450
    VCLKSIILLN SGVYTFLSST LKSLEEKDHI HRVLDKINDT LIHLMAKAGL 500
    TLQQQHRRLA QLLLILSHIR HMSNKGMEHL YNMKCKNVVP LYDLLLEMLD 550
    AHRLHAPASR MGVPPEEPSQ SQLTTTSSTS AHSLQTYYIP PEAEGFPNTI 600
    Length:600
    Mass (Da):67,030
    Last modified:January 1, 1988 - v1
    Checksum:iC9C7D8CACE0F57D8
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti488 – 4881N → T in CAA43411. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y00102 mRNA. Translation: CAA68287.1.
    X61098 mRNA. Translation: CAA43411.1.
    PIRiS07379. QRRTE.
    RefSeqiNP_036821.1. NM_012689.1.
    UniGeneiRn.10595.
    Rn.231229.

    Genome annotation databases

    GeneIDi24890.
    KEGGirno:24890.
    UCSCiRGD:2581. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y00102 mRNA. Translation: CAA68287.1 .
    X61098 mRNA. Translation: CAA43411.1 .
    PIRi S07379. QRRTE.
    RefSeqi NP_036821.1. NM_012689.1.
    UniGenei Rn.10595.
    Rn.231229.

    3D structure databases

    ProteinModelPortali P06211.
    SMRi P06211. Positions 185-258, 306-555.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 247000. 9 interactions.
    DIPi DIP-41279N.
    IntActi P06211. 2 interactions.
    MINTi MINT-234578.
    STRINGi 10116.ENSRNOP00000026350.

    Chemistry

    BindingDBi P06211.
    ChEMBLi CHEMBL2094114.
    GuidetoPHARMACOLOGYi 620.

    PTM databases

    PhosphoSitei P06211.

    Proteomic databases

    PaxDbi P06211.
    PRIDEi P06211.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 24890.
    KEGGi rno:24890.
    UCSCi RGD:2581. rat.

    Organism-specific databases

    CTDi 2099.
    RGDi 2581. Esr1.

    Phylogenomic databases

    eggNOGi NOG320746.
    HOGENOMi HOG000233468.
    HOVERGENi HBG108344.
    InParanoidi P06211.
    KOi K08550.
    PhylomeDBi P06211.

    Miscellaneous databases

    NextBioi 604756.
    PROi P06211.

    Gene expression databases

    Genevestigatori P06211.

    Family and domain databases

    Gene3Di 1.10.565.10. 2 hits.
    3.30.50.10. 1 hit.
    InterProi IPR008946. Nucl_hormone_rcpt_ligand-bd.
    IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
    IPR024178. Oest_rcpt/oest-rel_rcp.
    IPR001292. Oestr_rcpt.
    IPR024736. Oestrogen-typ_rcpt_final_C_dom.
    IPR001723. Str_hrmn_rcpt.
    IPR001628. Znf_hrmn_rcpt.
    IPR013088. Znf_NHR/GATA.
    [Graphical view ]
    Pfami PF12743. ESR1_C. 1 hit.
    PF00104. Hormone_recep. 1 hit.
    PF02159. Oest_recep. 1 hit.
    PF00105. zf-C4. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF500101. ER-a. 1 hit.
    PIRSF002527. ER-like_NR. 1 hit.
    PRINTSi PR00543. OESTROGENR.
    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. Muramatsu M.
      Submitted (MAR-1987) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Wistar.
    2. "Molecular cloning and characterization of rat estrogen receptor cDNA."
      Koike S., Sakai M.
      Nucleic Acids Res. 15:2499-2513(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. Maggi A.M.A.
      Submitted (JUN-1991) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Sprague-Dawley.
      Tissue: Uterus.
    4. Cited for: INTERACTION WITH UBE1C.
    5. "The NMDAR subunit NR3A interacts with microtubule-associated protein 1S in the brain."
      Eriksson M., Samuelsson H., Samuelsson E.-B., Liu L., McKeehan W.L., Benedikz E., Sundstroem E.
      Biochem. Biophys. Res. Commun. 361:127-132(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MAP1S.
    6. "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 nameiESR1_RAT
    AccessioniPrimary (citable) accession number: P06211
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1988
    Last sequence update: January 1, 1988
    Last modified: October 1, 2014
    This is version 162 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity. The hormone-receptor complex appears to recognize discrete DNA sequences upstream of transcriptional start sites.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3