ESR1_MOUSE
ID ESR1_MOUSE Reviewed; 599 AA.
AC P19785; Q9JJT5; Q9QY51; Q9QY52;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 238.
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, Estr, Estra, Nr3a1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Uterus;
RX PubMed=2484714; DOI=10.1210/mend-1-10-735;
RA White R., Lees J.A., Needham M., Ham J., Parker M.;
RT "Structural organization and expression of the mouse estrogen receptor.";
RL Mol. Endocrinol. 1:735-744(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=10899303; DOI=10.1016/s0014-5793(00)01750-6;
RA Kos M., O'Brien S., Flouriot G., Gannon F.;
RT "Tissue-specific expression of multiple mRNA variants of the mouse estrogen
RT receptor alpha gene.";
RL FEBS Lett. 477:15-20(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 269-599, AND VARIANT GLN-591.
RC STRAIN=B10.S/J, and SJL/J; TISSUE=Spleen;
RA Ma R.Z., Teuscher C.;
RT "Screening for candidate genes of mouse autoimmune diseases.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP INTERACTION WITH NRIP1.
RX PubMed=7641693; DOI=10.1002/j.1460-2075.1995.tb00044.x;
RA Cavailles V., Dauvois S., L'Horset F., Lopez G., Hoare S., Kushner P.J.,
RA Parker M.G.;
RT "Nuclear factor RIP140 modulates transcriptional activation by the estrogen
RT receptor.";
RL EMBO J. 14:3741-3751(1995).
RN [6]
RP INTERACTION WITH POU4F2.
RX PubMed=9448000; DOI=10.1128/mcb.18.2.1029;
RA Budhram-Mahadeo V., Parker M., Latchman D.S.;
RT "POU transcription factors Brn-3a and Brn-3b interact with the estrogen
RT receptor and differentially regulate transcriptional activity via an
RT estrogen response element.";
RL Mol. Cell. Biol. 18:1029-1041(1998).
RN [7]
RP FUNCTION, INTERACTION WITH NCOA1, AND MUTAGENESIS OF ILE-362; LYS-366;
RP LEU-376; VAL-380 AND LEU-543.
RX PubMed=10207113; DOI=10.1128/mcb.19.5.3895;
RA Mak H.Y., Hoare S., Henttu P.M., Parker M.G.;
RT "Molecular determinants of the estrogen receptor-coactivator interface.";
RL Mol. Cell. Biol. 19:3895-3903(1999).
RN [8]
RP FUNCTION, INTERACTION WITH NCOA1, AND MUTAGENESIS OF PHE-371; LEU-508;
RP ALA-509; LEU-512; LEU-515; GLY-525; ASP-542; 543-LEU-LEU-544; GLU-546;
RP 547-MET-LEU-548 AND ASP-549.
RX PubMed=10840033; DOI=10.1074/jbc.m002497200;
RA Valentine J.E., Kalkhoven E., White R., Hoare S., Parker M.G.;
RT "Mutations in the estrogen receptor ligand binding domain discriminate
RT between hormone-dependent transactivation and transrepression.";
RL J. Biol. Chem. 275:25322-25329(2000).
RN [9]
RP INTERACTION WITH FAM120B.
RX PubMed=17595322; DOI=10.1210/me.2006-0520;
RA Li D., Kang Q., Wang D.-M.;
RT "Constitutive coactivator of peroxisome proliferator-activated receptor
RT (PPARgamma), a novel coactivator of PPARgamma that promotes adipogenesis.";
RL Mol. Endocrinol. 21:2320-2333(2007).
RN [10]
RP GLYCOSYLATION AT THR-575.
RX PubMed=8999954; DOI=10.1074/jbc.272.4.2421;
RA Jiang M.S., Hart G.W.;
RT "A subpopulation of estrogen receptors are modified by O-linked N-
RT acetylglucosamine.";
RL J. Biol. Chem. 272:2421-2428(1997).
RN [11]
RP GLYCOSYLATION AT SER-10; THR-50 AND THR-575.
RX PubMed=11226831; DOI=10.1016/s0960-0760(00)00167-9;
RA Cheng X., Hart G.W.;
RT "Glycosylation of the murine estrogen receptor-alpha.";
RL J. Steroid Biochem. Mol. Biol. 75:147-158(2000).
RN [12]
RP INTERACTION WITH NCOA3.
RX PubMed=9192892; DOI=10.1038/42652;
RA Torchia J., Rose D.W., Inostroza J., Kamei Y., Westin S., Glass C.K.,
RA Rosenfeld M.G.;
RT "The transcriptional co-activator p/CIP binds CBP and mediates nuclear-
RT receptor function.";
RL Nature 387:677-684(1997).
RN [13]
RP INTERACTION WITH NCOA6.
RX PubMed=10788465; DOI=10.1074/jbc.275.18.13510;
RA Zhu Y.-J., Kan L., Qi C., Kanwar Y.S., Yeldandi A.V., Rao M.S., Reddy J.K.;
RT "Isolation and characterization of peroxisome proliferator-activated
RT receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR.";
RL J. Biol. Chem. 275:13510-13516(2000).
RN [14]
RP INTERACTION WITH RBM39.
RX PubMed=11704680; DOI=10.1074/jbc.m110417200;
RA Jung D.-J., Na S.-Y., Na D.S., Lee J.W.;
RT "Molecular cloning and characterization of CAPER, a novel coactivator of
RT activating protein-1 and estrogen receptors.";
RL J. Biol. Chem. 277:1229-1234(2002).
RN [15]
RP INTERACTION WITH PHB2.
RX PubMed=15140878; DOI=10.1074/jbc.m312300200;
RA Kurtev V., Margueron R., Kroboth K., Ogris E., Cavailles V., Seiser C.;
RT "Transcriptional regulation by the repressor of estrogen receptor activity
RT via recruitment of histone deacetylases.";
RL J. Biol. Chem. 279:24834-24843(2004).
RN [16]
RP INTERACTION WITH SLC30A9.
RX PubMed=15988012; DOI=10.1128/mcb.25.14.5965-5972.2005;
RA Chen Y.-H., Kim J.H., Stallcup M.R.;
RT "GAC63, a GRIP1-dependent nuclear receptor coactivator.";
RL Mol. Cell. Biol. 25:5965-5972(2005).
RN [17]
RP INTERACTION WITH FOXL2.
RX PubMed=20005806; DOI=10.1016/j.cell.2009.11.021;
RA Uhlenhaut N.H., Jakob S., Anlag K., Eisenberger T., Sekido R., Kress J.,
RA Treier A.C., Klugmann C., Klasen C., Holter N.I., Riethmacher D.,
RA Schutz G., Cooney A.J., Lovell-Badge R., Treier M.;
RT "Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation.";
RL Cell 139:1130-1142(2009).
RN [18]
RP PALMITOYLATION AT CYS-451, AND MUTAGENESIS OF CYS-451.
RX PubMed=22031296; DOI=10.1091/mbc.e11-07-0638;
RA Pedram A., Razandi M., Deschenes R.J., Levin E.R.;
RT "DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors.";
RL Mol. Biol. Cell 23:188-199(2012).
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. {ECO:0000269|PubMed:10207113,
CC ECO:0000269|PubMed:10840033}.
CC -!- SUBUNIT: Interacts with BCAS3. Binds DNA as a homodimer (By
CC similarity). Can form a heterodimer with ESR2 (By similarity).
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 (By similarity).
CC Interacts with FAM120B, FOXL2, PHB2 and SLC30A9. Interacts with
CC coactivators NCOA3 and NCOA6. Interacts with STK3/MST2 only in the
CC presence of SAV1 and vice-versa. Binds to CSNK1D. Interacts with NCOA2;
CC NCOA2 can interact with ESR1 AF-1 and AF-2 domains simultaneously and
CC mediate their transcriptional synergy. Interacts with DDX5. Interacts
CC with NCOA1; the interaction seems to require a self-association of N-
CC terminal and C-terminal regions. Interacts with ZNF366, DDX17, NFKB1,
CC RELA, SP1 and SP3. Interacts with NRIP1 (By similarity). Interacts with
CC GPER1; the interaction occurs in an estrogen-dependent manner.
CC Interacts with CLOCK and the interaction is stimulated by estrogen (By
CC similarity). Interacts with BCAS3. Interacts with TRIP4 (ufmylated);
CC estrogen dependent (By similarity). Interacts with LMTK3; the
CC interaction phosphorylates ESR1 (in vitro) and protects it against
CC proteasomal degradation. Interacts with CCAR2 (via N-terminus) in a
CC ligand-independent manner. Interacts with ZFHX3 (By similarity).
CC Interacts with SFR1 in a ligand-dependent and -independent manner (By
CC similarity). Interacts with DCAF13, LATS1 and DCAF1; regulates ESR1
CC ubiquitination and ubiquitin-mediated proteasomal degradation (By
CC similarity). Interacts (via DNA-binding domain) with POU4F2 isoform 2
CC (C-terminus); this interaction increases the estrogen receptor ESR1
CC transcriptional activity in a DNA- and ligand 17-beta-estradiol-
CC independent manner (PubMed:9448000). Interacts with ESRRB isoform 1 (By
CC similarity). Interacts with UBE3A and WBP2 (By similarity). Interacts
CC with GTF2B (By similarity). Interacts with RBM39 (PubMed:11704680). In
CC the 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). {ECO:0000250|UniProtKB:P03372,
CC ECO:0000269|PubMed:10207113, ECO:0000269|PubMed:10788465,
CC ECO:0000269|PubMed:10840033, ECO:0000269|PubMed:11704680,
CC ECO:0000269|PubMed:15988012, ECO:0000269|PubMed:17595322,
CC ECO:0000269|PubMed:20005806, ECO:0000269|PubMed:7641693,
CC ECO:0000269|PubMed:9192892, ECO:0000269|PubMed:9448000}.
CC -!- INTERACTION:
CC P19785; Q00175: Pgr; NbExp=5; IntAct=EBI-346765, EBI-346821;
CC P19785; Q15788: NCOA1; Xeno; NbExp=3; IntAct=EBI-346765, EBI-455189;
CC P19785; O94763: URI1; Xeno; NbExp=2; IntAct=EBI-346765, EBI-357067;
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: Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably
CC enhances transcriptional activity. Dephosphorylation at Ser-122 by
CC PPP5C inhibits its transactivation activity (By similarity).
CC Phosphorylated by LMTK3 (in vitro) (By similarity).
CC {ECO:0000250|UniProtKB:P03372}.
CC -!- PTM: Ubiquitinated. Deubiquitinated by OTUB1 (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Palmitoylated at Cys-451 by ZDHHC7 and ZDHHC21. This modification
CC is 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.
CC {ECO:0000269|PubMed:22031296}.
CC -!- PTM: Ubiquitinated; regulated by LATS1 via DCAF1 it leads to ESR1
CC proteasomal degradation. Deubiquitinated by OTUB1.
CC {ECO:0000250|UniProtKB:P03372}.
CC -!- PTM: Dimethylated by PRMT1 at Arg-264. The methylation may favor
CC cytoplasmic localization. Demethylated by JMJD6 at Arg-264.
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; M38651; AAA37580.1; -; mRNA.
DR EMBL; AK036627; BAC29510.1; -; mRNA.
DR EMBL; AK041525; BAC30973.1; -; mRNA.
DR EMBL; AJ276597; CAB85618.1; -; Genomic_DNA.
DR EMBL; AF128221; AAF22562.1; -; mRNA.
DR EMBL; AF128220; AAF22561.1; -; mRNA.
DR CCDS; CCDS56678.1; -.
DR PIR; A40061; QRMSE.
DR RefSeq; NP_001289460.1; NM_001302531.1.
DR RefSeq; NP_001289461.1; NM_001302532.1.
DR RefSeq; NP_031982.1; NM_007956.5.
DR RefSeq; XP_006512496.1; XM_006512433.3.
DR RefSeq; XP_006512497.1; XM_006512434.3.
DR RefSeq; XP_006512498.1; XM_006512435.2.
DR RefSeq; XP_011241368.1; XM_011243066.2.
DR RefSeq; XP_011241369.1; XM_011243067.2.
DR RefSeq; XP_011241370.1; XM_011243068.2.
DR AlphaFoldDB; P19785; -.
DR SMR; P19785; -.
DR BioGRID; 199521; 33.
DR IntAct; P19785; 9.
DR MINT; P19785; -.
DR STRING; 10090.ENSMUSP00000070070; -.
DR BindingDB; P19785; -.
DR ChEMBL; CHEMBL3065; -.
DR DrugCentral; P19785; -.
DR GuidetoPHARMACOLOGY; 620; -.
DR GlyConnect; 145; 1 O-Linked glycan (1 site).
DR GlyGen; P19785; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P19785; -.
DR PhosphoSitePlus; P19785; -.
DR SwissPalm; P19785; -.
DR PaxDb; P19785; -.
DR PRIDE; P19785; -.
DR ProteomicsDB; 275478; -.
DR Antibodypedia; 739; 4181 antibodies from 55 providers.
DR DNASU; 13982; -.
DR Ensembl; ENSMUST00000067086; ENSMUSP00000070070; ENSMUSG00000019768.
DR Ensembl; ENSMUST00000105589; ENSMUSP00000101214; ENSMUSG00000019768.
DR Ensembl; ENSMUST00000105590; ENSMUSP00000101215; ENSMUSG00000019768.
DR GeneID; 13982; -.
DR KEGG; mmu:13982; -.
DR UCSC; uc007egu.3; mouse.
DR CTD; 2099; -.
DR MGI; MGI:1352467; Esr1.
DR VEuPathDB; HostDB:ENSMUSG00000019768; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000158133; -.
DR HOGENOM; CLU_007368_11_1_1; -.
DR InParanoid; P19785; -.
DR OMA; QCDARDE; -.
DR OrthoDB; 487299at2759; -.
DR PhylomeDB; P19785; -.
DR TreeFam; TF323751; -.
DR Reactome; R-MMU-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-MMU-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-8866910; TFAP2 (AP-2) family regulates transcription of growth factors and their receptors.
DR Reactome; R-MMU-8931987; RUNX1 regulates estrogen receptor mediated transcription.
DR Reactome; R-MMU-8939211; ESR-mediated signaling.
DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-MMU-9018519; Estrogen-dependent gene expression.
DR BioGRID-ORCS; 13982; 5 hits in 77 CRISPR screens.
DR ChiTaRS; Esr1; mouse.
DR PRO; PR:P19785; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P19785; protein.
DR Bgee; ENSMUSG00000019768; Expressed in gastrula and 204 other tissues.
DR ExpressionAtlas; P19785; baseline and differential.
DR Genevisible; P19785; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0000791; C:euchromatin; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0043204; C:perikaryon; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0030315; C:T-tubule; ISO:MGI.
DR GO; GO:0043195; C:terminal bouton; ISO:MGI.
DR GO; GO:0097550; C:transcription preinitiation complex; ISO:MGI.
DR GO; GO:0005667; C:transcription regulator complex; ISO:MGI.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0034056; F:estrogen response element binding; ISO:MGI.
DR GO; GO:0042562; F:hormone binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0030284; F:nuclear estrogen receptor activity; ISO:MGI.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; ISO:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; IDA:MGI.
DR GO; GO:0003707; F:nuclear steroid receptor activity; ISO:MGI.
DR GO; GO:0036312; F:phosphatidylinositol 3-kinase regulatory subunit binding; ISO:MGI.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0005496; F:steroid binding; ISS:UniProtKB.
DR GO; GO:0017025; F:TBP-class protein binding; ISO:MGI.
DR GO; GO:0001093; F:TFIIB-class transcription factor binding; ISO:MGI.
DR GO; GO:0001223; F:transcription coactivator binding; ISO:MGI.
DR GO; GO:0001221; F:transcription coregulator binding; ISO:MGI.
DR GO; GO:0001222; F:transcription corepressor binding; ISO:MGI.
DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
DR GO; GO:0031798; F:type 1 metabotropic glutamate receptor binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0008209; P:androgen metabolic process; IMP:MGI.
DR GO; GO:0001547; P:antral ovarian follicle growth; IMP:MGI.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IDA:UniProtKB.
DR GO; GO:0071391; P:cellular response to estrogen stimulus; IMP:MGI.
DR GO; GO:0002064; P:epithelial cell development; IMP:MGI.
DR GO; GO:0060750; P:epithelial cell proliferation involved in mammary gland duct elongation; IMP:MGI.
DR GO; GO:0048144; P:fibroblast proliferation; IMP:MGI.
DR GO; GO:0030520; P:intracellular estrogen receptor signaling pathway; ISO:MGI.
DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IMP:MGI.
DR GO; GO:0060749; P:mammary gland alveolus development; IMP:MGI.
DR GO; GO:0060745; P:mammary gland branching involved in pregnancy; IMP:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0046325; P:negative regulation of glucose import; ISO:MGI.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:1903799; P:negative regulation of miRNA maturation; ISO:MGI.
DR GO; GO:0045839; P:negative regulation of mitotic nuclear division; NAS:UniProtKB.
DR GO; GO:1901215; P:negative regulation of neuron death; ISO:MGI.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0090209; P:negative regulation of triglyceride metabolic process; ISO:MGI.
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:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:MGI.
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:0045899; P:positive regulation of RNA polymerase II transcription preinitiation complex assembly; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0060527; P:prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis; IMP:MGI.
DR GO; GO:0060523; P:prostate epithelial cord elongation; IMP:MGI.
DR GO; GO:0071168; P:protein localization to chromatin; ISO:MGI.
DR GO; GO:0060687; P:regulation of branching involved in prostate gland morphogenesis; IMP:MGI.
DR GO; GO:1904035; P:regulation of epithelial cell apoptotic process; IMP:MGI.
DR GO; GO:0050727; P:regulation of inflammatory response; IMP:MGI.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0034121; P:regulation of toll-like receptor signaling pathway; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0032355; P:response to estradiol; ISO:MGI.
DR GO; GO:0043627; P:response to estrogen; ISO:MGI.
DR GO; GO:0060011; P:Sertoli cell proliferation; ISO:MGI.
DR GO; GO:0048863; P:stem cell differentiation; IDA:CAFA.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0060065; P:uterus development; IGI:MGI.
DR GO; GO:0060068; P:vagina development; IGI:MGI.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR024178; Est_rcpt/est-rel_rcp.
DR InterPro; IPR001292; Estr_rcpt.
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 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; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein 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..599
FT /note="Estrogen receptor"
FT /id="PRO_0000053621"
FT DOMAIN 315..551
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 189..254
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 189..209
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 225..249
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..188
FT /note="Modulating (transactivation AF-1); mediates
FT interaction with MACROD1"
FT /evidence="ECO:0000250"
FT REGION 35..178
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 147..175
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 189..314
FT /note="Mediates interaction with DNTTIP2"
FT /evidence="ECO:0000250"
FT REGION 255..314
FT /note="Hinge"
FT REGION 266..599
FT /note="Interaction with AKAP13"
FT /evidence="ECO:0000250"
FT REGION 268..599
FT /note="Self-association"
FT /evidence="ECO:0000250"
FT REGION 315..599
FT /note="Transactivation AF-2"
FT /evidence="ECO:0000250"
FT REGION 557..581
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 564..581
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 108
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000250|UniProtKB:P03372"
FT MOD_RES 110
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000250|UniProtKB:P03372"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03372"
FT MOD_RES 171
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P03372"
FT MOD_RES 264
FT /note="Asymmetric dimethylarginine; by PRMT1"
FT /evidence="ECO:0000250|UniProtKB:P03372"
FT MOD_RES 541
FT /note="Phosphotyrosine; by Tyr-kinases"
FT /evidence="ECO:0000250|UniProtKB:P03372"
FT LIPID 451
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:22031296"
FT CARBOHYD 10
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000269|PubMed:11226831"
FT CARBOHYD 50
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000269|PubMed:11226831"
FT CARBOHYD 575
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000269|PubMed:11226831,
FT ECO:0000269|PubMed:8999954"
FT /id="CAR_000137"
FT VARIANT 591
FT /note="E -> Q (in strain: SJL/J)"
FT /evidence="ECO:0000269|Ref.4"
FT MUTAGEN 362
FT /note="I->A: No effect on transcriptional activity and
FT estrogen-induced interaction with NCOA1. Abolishes
FT estrogen-induced interaction with NCOA1; when associated
FT with A-376 and A-380."
FT /evidence="ECO:0000269|PubMed:10207113"
FT MUTAGEN 362
FT /note="I->D: Abolishes transcriptional activity and
FT estrogen-induced interaction with NCOA1."
FT /evidence="ECO:0000269|PubMed:10207113"
FT MUTAGEN 366
FT /note="K->A: Greatly reduces transcriptional activity and
FT estrogen-induced interaction with NCOA1."
FT /evidence="ECO:0000269|PubMed:10207113"
FT MUTAGEN 366
FT /note="K->D: Abolishes transcriptional activity and
FT estrogen-induced interaction with NCOA1."
FT /evidence="ECO:0000269|PubMed:10207113"
FT MUTAGEN 366
FT /note="K->L: Reduces transcriptional activity and estrogen-
FT induced interaction with NCOA1."
FT /evidence="ECO:0000269|PubMed:10207113"
FT MUTAGEN 371
FT /note="F->A: Abolishes estrogen-dependent NF-kappa B
FT transcriptional repression, impairs transcriptional
FT activity, abolishes estrogen-induced interaction with
FT NCOA1."
FT /evidence="ECO:0000269|PubMed:10840033"
FT MUTAGEN 376
FT /note="L->A: Reduces transcriptional activity, no effect on
FT estrogen-induced interaction with NCOA1. Abolishes
FT estrogen-induced interaction with NCOA1; when associated
FT with A-362 and A-380."
FT /evidence="ECO:0000269|PubMed:10207113"
FT MUTAGEN 376
FT /note="L->D: Reduces transcriptional activity and estrogen-
FT induced interaction with NCOA1."
FT /evidence="ECO:0000269|PubMed:10207113"
FT MUTAGEN 380
FT /note="V->A: No effect on transcriptional activity and
FT estrogen-induced interaction with NCOA1. Abolishes
FT estrogen-induced interaction with NCOA1; when associated
FT with A-362 and A-376."
FT /evidence="ECO:0000269|PubMed:10207113"
FT MUTAGEN 380
FT /note="V->D: Abolishes transcriptional activity and
FT estrogen-induced interaction with NCOA1."
FT /evidence="ECO:0000269|PubMed:10207113"
FT MUTAGEN 451
FT /note="C->A: Loss of ZDHHC7 and ZDHHC21 binding. Loss of
FT palmitoylation."
FT /evidence="ECO:0000269|PubMed:22031296"
FT MUTAGEN 508
FT /note="L->A: Reduces DNA-binding, attenuates
FT transcriptional activity, does not effect estrogen-
FT dependent NF-kappa B transcriptional repression; when
FT associated with E-512 and E-515."
FT /evidence="ECO:0000269|PubMed:10840033"
FT MUTAGEN 508
FT /note="L->E: Abolishes DNA-binding, abolishes
FT transcriptional activity and estrogen-dependent NF-kappa B
FT transcriptional repression; when associated with E-512 and
FT E-515."
FT /evidence="ECO:0000269|PubMed:10840033"
FT MUTAGEN 509
FT /note="A->E: Reduces DNA-binding,, attenuates
FT transcriptional activity, does not effect estrogen-
FT dependent NF-kappa B transcriptional repression."
FT /evidence="ECO:0000269|PubMed:10840033"
FT MUTAGEN 512
FT /note="L->A: Reduces DNA-binding, attenuates
FT transcriptional activity, does not effect estrogen-
FT dependent NF-kappa B transcriptional repression; when
FT associated with E-508 and E-515."
FT /evidence="ECO:0000269|PubMed:10840033"
FT MUTAGEN 512
FT /note="L->E: Abolishes DNA-binding, abolishes
FT transcriptional activity and estrogen-dependent NF-kappa B
FT transcriptional repression; when associated with E-508 and
FT E-515."
FT /evidence="ECO:0000269|PubMed:10840033"
FT MUTAGEN 515
FT /note="L->A: Reduces DNA-binding, attenuates
FT transcriptional activity, does not effect estrogen-
FT dependent NF-kappa B transcriptional repression; when
FT associated with E-508 and E-512."
FT /evidence="ECO:0000269|PubMed:10840033"
FT MUTAGEN 515
FT /note="L->E: Abolishes DNA-binding, abolishes
FT transcriptional activity and estrogen-dependent NF-kappa B
FT transcriptional repression; when associated with E-508 and
FT E-512."
FT /evidence="ECO:0000269|PubMed:10840033"
FT MUTAGEN 525
FT /note="G->R: Abolishes estrogen binding; impairs repression
FT of NF-kappa activity."
FT /evidence="ECO:0000269|PubMed:10840033"
FT MUTAGEN 542
FT /note="D->N: Abolishes estrogen-dependent NF-kappa B
FT transcriptional repression, impairs transcriptional
FT activity, impairs estrogen-induced interaction with NCOA1;
FT when associated with Q-546 and N-548."
FT /evidence="ECO:0000269|PubMed:10840033"
FT MUTAGEN 543..544
FT /note="LL->AA: Abolishes estrogen-dependent NF-kappa B
FT transcriptional repression, abolishes estrogen-induced
FT interaction with NCOA1."
FT /evidence="ECO:0000269|PubMed:10840033"
FT MUTAGEN 543
FT /note="L->A: Abolishes estrogen-induced interaction with
FT NCOA1."
FT /evidence="ECO:0000269|PubMed:10207113"
FT MUTAGEN 546
FT /note="E->Q: Abolishes estrogen-dependent NF-kappa B
FT transcriptional repression, impairs transcriptional
FT activity, impairs estrogen-induced interaction with NCOA1;
FT when associated with N-542 and N-548."
FT /evidence="ECO:0000269|PubMed:10840033"
FT MUTAGEN 547..548
FT /note="ML->AA: No effect on estrogen-dependent NF-kappa B
FT transcriptional repression, greatly impairs transcriptional
FT activity, abolishes estrogen-induced interaction with
FT NCOA1."
FT /evidence="ECO:0000269|PubMed:10840033"
FT MUTAGEN 549
FT /note="D->N: Abolishes estrogen-dependent NF-kappa B
FT transcriptional repression, impairs transcriptional
FT activity, impairs estrogen-induced interaction with NCOA1;
FT when associated with N-542 and Q-546."
FT /evidence="ECO:0000269|PubMed:10840033"
FT CONFLICT 269
FT /note="L -> M (in Ref. 4; AAF22561)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 599 AA; 66955 MW; 05F5E2FC21CC0A8B CRC64;
MTMTLHTKAS GMALLHQIQG NELEPLNRPQ LKMPMERALG EVYVDNSKPT VFNYPEGAAY
EFNAAAAAAA AASAPVYGQS GIAYGPGSEA AAFSANSLGA FPQLNSVSPS PLMLLHPPPQ
LSPFLHPHGQ QVPYYLENEP SAYAVRDTGP PAFYRSNSDN RRQNGRERLS SSNEKGNMIM
ESAKETRYCA VCNDYASGYH YGVWSCEGCK AFFKRSIQGH NDYMCPATNQ CTIDKNRRKS
CQACRLRKCY EVGMMKGGIR KDRRGGRMLK HKRQRDDLEG RNEMGASGDM RAANLWPSPL
VIKHTKKNSP ALSLTADQMV SALLDAEPPM IYSEYDPSRP FSEASMMGLL TNLADRELVH
MINWAKRVPG FGDLNLHDQV HLLECAWLEI LMIGLVWRSM EHPGKLLFAP NLLLDRNQGK
CVEGMVEIFD MLLATSSRFR MMNLQGEEFV CLKSIILLNS GVYTFLSSTL KSLEEKDHIH
RVLDKITDTL IHLMAKAGLT LQQQHRRLAQ LLLILSHIRH MSNKGMEHLY NMKCKNVVPL
YDLLLEMLDA HRLHAPASRM GVPPEEPSQT QLATTSSTSA HSLQTYYIPP EAEGFPNTI
