ID   ESR1_HORSE              Reviewed;         594 AA.
AC   Q9TV98;
DT   11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 170.
DE   RecName: Full=Estrogen receptor;
DE            Short=ER;
DE   AltName: Full=ER-alpha;
DE   AltName: Full=Estradiol receptor;
DE   AltName: Full=Nuclear receptor subfamily 3 group A member 1;
GN   Name=ESR1; Synonyms=ESR, NR3A1;
OS   Equus caballus (Horse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX   NCBI_TaxID=9796;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   McDowell K.J., Adams M.H., Green M.L., Cleaver B.D., Sharp D.C.;
RL   Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Nuclear hormone receptor. The steroid hormones and their
CC       receptors are involved in the regulation of eukaryotic gene expression
CC       and affect cellular proliferation and differentiation in target
CC       tissues. Ligand-dependent nuclear transactivation involves either
CC       direct homodimer binding to a palindromic estrogen response element
CC       (ERE) sequence or association with other DNA-binding transcription
CC       factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-
CC       independent signaling. Ligand binding induces a conformational change
CC       allowing subsequent or combinatorial association with multiprotein
CC       coactivator complexes through LXXLL motifs of their respective
CC       components. Mutual transrepression occurs between the estrogen receptor
CC       (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-
CC       B DNA-binding activity and inhibits NF-kappa-B-mediated transcription
CC       from the IL6 promoter and displace RELA/p65 and associated coregulators
CC       from the promoter. Recruited to the NF-kappa-B response element of the
CC       CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B
CC       components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act
CC       synergistically with NF-kappa-B to activate transcription involving
CC       respective recruitment adjacent response elements; the function
CC       involves CREBBP. Can activate the transcriptional activity of TFF1.
CC       Also mediates membrane-initiated estrogen signaling involving various
CC       kinase cascades.Essential for MTA1-mediated transcriptional regulation
CC       of BRCA1 and BCAS3 (By similarity). Maintains neuronal survival in
CC       response to ischemic reperfusion injury when in the presence of
CC       circulating estradiol (17-beta-estradiol/E2) (By similarity).
CC       {ECO:0000250, ECO:0000250|UniProtKB:P06211}.
CC   -!- SUBUNIT: Binds DNA as a homodimer. Can form a heterodimer with ESR2.
CC       Interacts with coactivator NCOA5. Interacts with PELP1, the interaction
CC       is enhanced by 17-beta-estradiol; the interaction increases ESR1
CC       transcriptional activity (By similarity). Interacts with NCOA7; the
CC       interaction is ligand-inducible. Interacts with AKAP13, CUEDC2, HEXIM1,
CC       KDM5A, MAP1S, SMARD1, and UBE1C. Interacts with MUC1; the interaction
CC       is stimulated by 7 beta-estradiol (E2) and enhances ESR1-mediated
CC       transcription. Interacts with DNTTIP2, and UIMC1. Interacts with
CC       KMT2D/MLL2. Interacts with ATAD2; the interaction is enhanced by
CC       estradiol. Interacts with KIF18A and LDB1. Interacts with RLIM (via its
CC       C-terminus). Interacts with MACROD1. Interacts with SH2D4A and PLCG.
CC       Interacts with SH2D4A; the interaction blocks binding to PLCG and
CC       inhibits estrogen-induced cell proliferation. Interacts with DYNLL1.
CC       Interacts with CCDC62; the interaction requires estradiol and appears
CC       to enhance the transcription of target genes. Interacts with NR2C1; the
CC       interaction prevents homodimerization of ESR1 and suppresses its
CC       transcriptional activity and cell growth. Interacts with DNAAF4.
CC       Interacts with PRMT2. Interacts with RBFOX2. Interacts with EP300; the
CC       interaction is estrogen-dependent and enhanced by CITED1. Interacts
CC       with CITED1; the interaction is estrogen-dependent. Interacts with
CC       FAM120B, FOXL2, PHB2 and SLC30A9. Interacts with coactivators NCOA3 and
CC       NCOA6. Interacts with STK3/MST2 only in the presence of SAV1 and vice-
CC       versa. Binds to CSNK1D. Interacts with NCOA2; NCOA2 can interact with
CC       ESR1 AF-1 and AF-2 domains simultaneously and mediate their
CC       transcriptional synergy. Interacts with DDX5. Interacts with NCOA1; the
CC       interaction seems to require a self-association of N-terminal and C-
CC       terminal regions. Interacts with ZNF366, DDX17, NFKB1, RELA, SP1 and
CC       SP3. Interacts with NRIP1. Interacts with GPER1; the interaction occurs
CC       in an estrogen-dependent manner. Interacts with CLOCK and the
CC       interaction is stimulated by estrogen. Interacts with TRIP4
CC       (ufmylated); estrogen dependent. Interacts with LMTK3; the interaction
CC       phosphorylates ESR1 (in vitro) and protects it against proteasomal
CC       degradation. Interacts with CCAR2 (via N-terminus) in a ligand-
CC       independent manner. Interacts with ZFHX3. Interacts with SFR1 in a
CC       ligand-dependent and -independent manner. Interacts with DCAF13, LATS1
CC       and DCAF1; regulates ESR1 ubiquitination and ubiquitin-mediated
CC       proteasomal degradation. Interacts (via DNA-binding domain) with POU4F2
CC       (C-terminus); this interaction increases the estrogen receptor ESR1
CC       transcriptional activity in a DNA- and ligand 17-beta-estradiol-
CC       independent manner. Interacts with ESRRB isoform 1. Interacts with
CC       UBE3A and WBP2. Interacts with GTF2B. Interacts with RBM39. In the
CC       absence of hormonal ligand, interacts with TACC1 (By similarity).
CC       Interacts with PI3KR1 or PI3KR2 and PTK2/FAK1 (By similarity).
CC       Interacts with SRC (By similarity). Interacts with BAG1; the
CC       interaction is promoted in the absence of estradiol (17-beta-
CC       estradiol/E2) (By similarity). Interacts with and ubiquitinated by
CC       STUB1; the interaction is promoted in the absence of estradiol (17-
CC       beta-estradiol/E2) (By similarity). Interacts with NEDD8 (By
CC       similarity). {ECO:0000250|UniProtKB:P03372,
CC       ECO:0000250|UniProtKB:P06211, ECO:0000250|UniProtKB:P19785}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC       Cytoplasm {ECO:0000250}. Golgi apparatus {ECO:0000250}. Cell membrane
CC       {ECO:0000250}. Note=Colocalizes with ZDHHC7 and ZDHHC21 in the Golgi
CC       apparatus where most probably palmitoylation occurs. Associated with
CC       the plasma membrane when palmitoylated. {ECO:0000250}.
CC   -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC       DNA-binding domain and a C-terminal ligand-binding domain. The
CC       modulating domain, also known as A/B or AF-1 domain has a ligand-
CC       independent transactivation function. The C-terminus contains a ligand-
CC       dependent transactivation domain, also known as E/F or AF-2 domain
CC       which overlaps with the ligand binding domain. AF-1 and AF-2 activate
CC       transcription independently and synergistically and act in a
CC       promoter- and cell-specific manner (By similarity). {ECO:0000250}.
CC   -!- PTM: Ubiquitinated; regulated by LATS1 via DCAF1 it leads to ESR1
CC       proteasomal degradation (By similarity). Deubiquitinated by OTUB1 (By
CC       similarity). Ubiquitinated by STUB1/CHIP; in the CA1 hippocampal region
CC       following loss of endogenous circulating estradiol (17-beta-
CC       estradiol/E2) (By similarity). {ECO:0000250|UniProtKB:P03372,
CC       ECO:0000250|UniProtKB:P06211}.
CC   -!- PTM: Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably
CC       enhances transcriptional activity. Dephosphorylation at Ser-118 by
CC       PPP5C inhibits its transactivation activity (By similarity).
CC       Phosphorylated by LMTK3 (in vitro) (By similarity).
CC       {ECO:0000250|UniProtKB:P03372}.
CC   -!- PTM: Palmitoylated at Cys-447 by ZDHHC7 and ZDHHC21. Palmitoylation is
CC       required for plasma membrane targeting and for rapid intracellular
CC       signaling via ERK and AKT kinases and cAMP generation, but not for
CC       signaling mediated by the nuclear hormone receptor (By similarity).
CC       {ECO:0000250}.
CC   -!- PTM: Dimethylated by PRMT1 at Arg-260. The methylation may favor
CC       cytoplasmic localization. Demethylated by JMJD6 at Arg-260.
CC       {ECO:0000250|UniProtKB:P03372}.
CC   -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AF124093; AAD17316.1; -; mRNA.
DR   RefSeq; NP_001075241.1; NM_001081772.1.
DR   AlphaFoldDB; Q9TV98; -.
DR   SMR; Q9TV98; -.
DR   STRING; 9796.ENSECAP00000020141; -.
DR   GlyCosmos; Q9TV98; 2 sites, No reported glycans.
DR   PaxDb; 9796-ENSECAP00000020141; -.
DR   GeneID; 791249; -.
DR   KEGG; ecb:791249; -.
DR   CTD; 2099; -.
DR   InParanoid; Q9TV98; -.
DR   OrthoDB; 5387678at2759; -.
DR   Proteomes; UP000002281; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0034056; F:estrogen response element binding; IBA:GO_Central.
DR   GO; GO:0030284; F:nuclear estrogen receptor activity; IEA:InterPro.
DR   GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR   GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR   GO; GO:0005496; F:steroid binding; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0071392; P:cellular response to estradiol stimulus; ISS:UniProtKB.
DR   GO; GO:0071391; P:cellular response to estrogen stimulus; IBA:GO_Central.
DR   GO; GO:0030520; P:intracellular estrogen receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; ISS:UniProtKB.
DR   GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR   GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; ISS:UniProtKB.
DR   GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
DR   GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISS:UniProtKB.
DR   GO; GO:0010863; P:positive regulation of phospholipase C activity; ISS:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   CDD; cd07171; NR_DBD_ER; 1.
DR   CDD; cd06949; NR_LBD_ER; 1.
DR   Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1.
DR   Gene3D; 1.10.565.10; Retinoid X Receptor; 1.
DR   InterPro; IPR024178; Est_rcpt/est-rel_rcp.
DR   InterPro; IPR001292; Estr_rcpt.
DR   InterPro; IPR046944; Estr_rcpt_N.
DR   InterPro; IPR035500; NHR-like_dom_sf.
DR   InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR   InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR   InterPro; IPR024736; Oestrogen-typ_rcpt_final_C_dom.
DR   InterPro; IPR001628; Znf_hrmn_rcpt.
DR   InterPro; IPR013088; Znf_NHR/GATA.
DR   PANTHER; PTHR48092:SF16; ESTROGEN RECEPTOR; 1.
DR   PANTHER; PTHR48092; KNIRPS-RELATED PROTEIN-RELATED; 1.
DR   Pfam; PF12743; ESR1_C; 1.
DR   Pfam; PF00104; Hormone_recep; 1.
DR   Pfam; PF02159; Oest_recep; 1.
DR   Pfam; PF00105; zf-C4; 1.
DR   PIRSF; PIRSF500101; ER-a; 1.
DR   PIRSF; PIRSF002527; ER-like_NR; 1.
DR   PRINTS; PR00543; OESTROGENR.
DR   PRINTS; PR00398; STRDHORMONER.
DR   PRINTS; PR00047; STROIDFINGER.
DR   SMART; SM00430; HOLI; 1.
DR   SMART; SM00399; ZnF_C4; 1.
DR   SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1.
DR   SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1.
DR   PROSITE; PS51843; NR_LBD; 1.
DR   PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR   PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE   2: Evidence at transcript level;
KW   Activator; Cell membrane; Cytoplasm; DNA-binding; Glycoprotein;
KW   Golgi apparatus; Lipid-binding; Lipoprotein; Membrane; Metal-binding;
KW   Methylation; Nucleus; Palmitate; Phosphoprotein; Receptor;
KW   Reference proteome; Steroid-binding; Transcription;
KW   Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT   CHAIN           1..594
FT                   /note="Estrogen receptor"
FT                   /id="PRO_0000053617"
FT   DOMAIN          311..546
FT                   /note="NR LBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT   DNA_BIND        185..250
FT                   /note="Nuclear receptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         185..205
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         221..245
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   REGION          1..184
FT                   /note="Modulating (transactivation AF-1); mediates
FT                   interaction with MACROD1"
FT                   /evidence="ECO:0000250"
FT   REGION          35..174
FT                   /note="Interaction with DDX5; self-association"
FT                   /evidence="ECO:0000250"
FT   REGION          35..47
FT                   /note="Required for interaction with NCOA1"
FT                   /evidence="ECO:0000250"
FT   REGION          152..173
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          185..310
FT                   /note="Mediates interaction with DNTTIP2"
FT                   /evidence="ECO:0000250"
FT   REGION          251..310
FT                   /note="Hinge"
FT   REGION          257..293
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          262..594
FT                   /note="Interaction with AKAP13"
FT                   /evidence="ECO:0000250"
FT   REGION          264..594
FT                   /note="Self-association"
FT                   /evidence="ECO:0000250"
FT   REGION          311..594
FT                   /note="Transactivation AF-2"
FT                   /evidence="ECO:0000250"
FT   REGION          551..575
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        267..282
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        558..575
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         104
FT                   /note="Phosphoserine; by CDK2"
FT                   /evidence="ECO:0000250|UniProtKB:P03372"
FT   MOD_RES         106
FT                   /note="Phosphoserine; by CDK2"
FT                   /evidence="ECO:0000250|UniProtKB:P03372"
FT   MOD_RES         118
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P03372"
FT   MOD_RES         167
FT                   /note="Phosphoserine; by CK2"
FT                   /evidence="ECO:0000250|UniProtKB:P03372"
FT   MOD_RES         260
FT                   /note="Asymmetric dimethylarginine; by PRMT1"
FT                   /evidence="ECO:0000250|UniProtKB:P03372"
FT   MOD_RES         536
FT                   /note="Phosphotyrosine; by Tyr-kinases"
FT                   /evidence="ECO:0000250|UniProtKB:P03372"
FT   LIPID           447
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        10
FT                   /note="O-linked (GlcNAc) serine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        570
FT                   /note="O-linked (GlcNAc) threonine"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   594 AA;  66104 MW;  DD36CA7C24C74B95 CRC64;
     MTMTLHTKAS GMALLHQIQG NELETLNLPQ FKIPLERPLG EVYVESSKPP VYDYPEGAAY
     DFNAAAAASA SVYGQSGLAY GPGSEAAAFG ANGLGGFPPL NSVSPSQLML LHPPPQLSPY
     LHPPGQQVPY YLENEPSGYS VCEAGPQAFY RPNADNRRQG GRERLASSGD KGSMAMESAK
     ETRYCAVCND YASGYHYGVW SCEGCKAFFK RSIQGHNDYM CPATNQCTID KNRRKSCQAC
     RLRKCYEVGM MKGGIRKDRR GGRMLKHKRQ RDDGEGRNEA GPSGDRRPAN FWPSPLLIKH
     TKKISPVLSL TAEQMISALL DAEPPVLYSE YDATRPFNEA SMMGLLTNLA DRELVHMINW
     AKRVPGFVDL SLHDQVHLLE CAWLEILMIG LVWRSMEHPG KLLFAPNLLL DRNQGKCVEG
     MVEIFDMLLA TSSRLRMMNL QGEEFVCLKS IILLNSGVYT FLSSTLKSLE EKDHIHRVLD
     KMTDTLIHLM AKAGLTLQQH RRLAQLLLIL SHIRHMSNKG MEHLYSMKCK NVVPLYDLLL
     EMLDAHRLHA PANHGGAPME ETNQSQLATT GSTSPHSMQT YYITGEAEGF PNTI
//