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Q9TV98

- ESR1_HORSE

UniProt

Q9TV98 - ESR1_HORSE

Protein

Estrogen receptor

Gene

ESR1

Organism
Equus caballus (Horse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      Previous versions | rss
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    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 bindingi185 – 25066Nuclear receptorPROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri185 – 20521NR C4-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri221 – 24525NR C4-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. estrogen receptor activity Source: InterPro
    2. sequence-specific DNA binding Source: InterPro
    3. sequence-specific DNA binding transcription factor activity Source: InterPro
    4. steroid binding Source: UniProtKB
    5. zinc ion binding Source: InterPro

    GO - Biological processi

    1. cellular response to estradiol stimulus Source: UniProtKB
    2. intracellular steroid hormone receptor signaling pathway Source: UniProtKB
    3. negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
    4. negative regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
    5. phospholipase C-activating G-protein coupled receptor signaling pathway Source: UniProtKB
    6. positive regulation of cytosolic calcium ion concentration Source: UniProtKB
    7. positive regulation of nitric oxide biosynthetic process Source: UniProtKB
    8. positive regulation of nitric-oxide synthase activity Source: UniProtKB
    9. positive regulation of phospholipase C activity Source: UniProtKB
    10. positive regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
    11. 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, NR3A1
    OrganismiEquus caballus (Horse)
    Taxonomic identifieri9796 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaPerissodactylaEquidaeEquus
    ProteomesiUP000002281: Unplaced

    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. Golgi apparatus Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB
    3. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Golgi apparatus, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 594594Estrogen receptorPRO_0000053617Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi10 – 101O-linked (GlcNAc)By similarity
    Modified residuei104 – 1041Phosphoserine; by CDK2By similarity
    Modified residuei106 – 1061Phosphoserine; by CDK2By similarity
    Modified residuei118 – 1181PhosphoserineBy similarity
    Modified residuei167 – 1671Phosphoserine; by CK2By similarity
    Modified residuei260 – 2601Asymmetric dimethylarginine; by PRMT1By similarity
    Lipidationi447 – 4471S-palmitoyl cysteineBy similarity
    Modified residuei536 – 5361Phosphotyrosine; by Tyr-kinasesBy similarity
    Glycosylationi570 – 5701O-linked (GlcNAc)By similarity

    Post-translational modificationi

    Ubiquitinated. Deubiquitinated by OTUB1 By similarity.By similarity
    Dimethylated by PRMT1 at Arg-260. The methylation may favor cytoplasmic localization By similarity.By similarity
    Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably enhances transcriptional activity. Dephosphorylation at Ser-118 by PPP5C inhibits its transactivation activity By similarity.By similarity
    Palmitoylated at Cys-447 by ZDHHC7 and ZDHHC21. Palmitoylation 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

    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. Interacts with GPER1; the interaction occurs in an estrogen-dependent manner. Interacts with CLOCK and the interaction is stimulated by estrogen By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ9TV98.
    SMRiQ9TV98. Positions 180-253, 301-549.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 184184Modulating (transactivation AF-1); mediates interaction with MACROD1By similarityAdd
    BLAST
    Regioni35 – 174140Interaction with DDX5; self-associationBy similarityAdd
    BLAST
    Regioni35 – 4713Required for interaction with NCOA1By similarityAdd
    BLAST
    Regioni185 – 310126Mediates interaction with DNTTIP2By similarityAdd
    BLAST
    Regioni251 – 31060HingeAdd
    BLAST
    Regioni262 – 594333Interaction with AKAP13By similarityAdd
    BLAST
    Regioni264 – 594331Self-associationBy similarityAdd
    BLAST
    Regioni311 – 594284Transactivation AF-2By similarityAdd
    BLAST
    Regioni311 – 550240Steroid-bindingAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi64 – 707Poly-Ala

    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 fingeri185 – 20521NR C4-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri221 – 24525NR C4-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG320746.
    HOGENOMiHOG000233468.
    HOVERGENiHBG108344.
    InParanoidiQ9TV98.
    KOiK08550.

    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. 1 hit.
    PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
    PS51030. NUCLEAR_REC_DBD_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9TV98-1 [UniParc]FASTAAdd to Basket

    « Hide

    MTMTLHTKAS GMALLHQIQG NELETLNLPQ FKIPLERPLG EVYVESSKPP    50
    VYDYPEGAAY DFNAAAAASA SVYGQSGLAY GPGSEAAAFG ANGLGGFPPL 100
    NSVSPSQLML LHPPPQLSPY LHPPGQQVPY YLENEPSGYS VCEAGPQAFY 150
    RPNADNRRQG GRERLASSGD KGSMAMESAK ETRYCAVCND YASGYHYGVW 200
    SCEGCKAFFK RSIQGHNDYM CPATNQCTID KNRRKSCQAC RLRKCYEVGM 250
    MKGGIRKDRR GGRMLKHKRQ RDDGEGRNEA GPSGDRRPAN FWPSPLLIKH 300
    TKKISPVLSL TAEQMISALL DAEPPVLYSE YDATRPFNEA SMMGLLTNLA 350
    DRELVHMINW AKRVPGFVDL SLHDQVHLLE CAWLEILMIG LVWRSMEHPG 400
    KLLFAPNLLL DRNQGKCVEG MVEIFDMLLA TSSRLRMMNL QGEEFVCLKS 450
    IILLNSGVYT FLSSTLKSLE EKDHIHRVLD KMTDTLIHLM AKAGLTLQQH 500
    RRLAQLLLIL SHIRHMSNKG MEHLYSMKCK NVVPLYDLLL EMLDAHRLHA 550
    PANHGGAPME ETNQSQLATT GSTSPHSMQT YYITGEAEGF PNTI 594
    Length:594
    Mass (Da):66,104
    Last modified:May 1, 2000 - v1
    Checksum:iDD36CA7C24C74B95
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF124093 mRNA. Translation: AAD17316.1.
    RefSeqiNP_001075241.1. NM_001081772.1.
    UniGeneiEca.13034.
    Eca.21644.

    Genome annotation databases

    GeneIDi791249.
    KEGGiecb:791249.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF124093 mRNA. Translation: AAD17316.1 .
    RefSeqi NP_001075241.1. NM_001081772.1.
    UniGenei Eca.13034.
    Eca.21644.

    3D structure databases

    ProteinModelPortali Q9TV98.
    SMRi Q9TV98. Positions 180-253, 301-549.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 791249.
    KEGGi ecb:791249.

    Organism-specific databases

    CTDi 2099.

    Phylogenomic databases

    eggNOGi NOG320746.
    HOGENOMi HOG000233468.
    HOVERGENi HBG108344.
    InParanoidi Q9TV98.
    KOi K08550.

    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. 1 hit.
    PROSITEi PS00031. NUCLEAR_REC_DBD_1. 1 hit.
    PS51030. NUCLEAR_REC_DBD_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. McDowell K.J., Adams M.H., Green M.L., Cleaver B.D., Sharp D.C.
      Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].

    Entry informationi

    Entry nameiESR1_HORSE
    AccessioniPrimary (citable) accession number: Q9TV98
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 11, 2001
    Last sequence update: May 1, 2000
    Last modified: October 1, 2014
    This is version 118 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3