Estrogen receptor
Also known as: ESR, ESR1, NR3A1
Function
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. Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity).
Classification
- Family (Pfam)
- PF12743 ESR1_C, PF00104 Hormone_recep, PF02159 Oest_recep, PF00105 zf-C4
- InterPro
- Est_rcpt/est-rel_rcp, Estr_rcpt, Estr_rcpt_N, NHR-like_dom_sf, Nucl_hrmn_rcpt_lig-bd, Nuclear_hormone_rcpt_NR3, Nuclear_hrmn_rcpt, Oestrogen-typ_rcpt_final_C_dom, Znf_hrmn_rcpt, Znf_NHR/GATA
- Functional cluster
- Homeobox & Zinc-Finger Transcription Factors
Experimental structures · PDB · 473
- 1A52 X-ray 2.80A
- 1ERE X-ray 3.10A
- 1ERR X-ray 2.60A
- 1G50 X-ray 2.90A
- 1GWQ X-ray 2.45A
- 1GWR X-ray 2.40A
- 1HCP NMR
- 1HCQ X-ray 2.40A
- 1L2I X-ray 1.95A
- 1PCG X-ray 2.70A
- 1QKT X-ray 2.20A
- 1QKU X-ray 3.20A
- … and 461 more
A predicted model is available from AlphaFold.
Gene Ontology · 60
- GO:0000785 chromatin
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0000791 euchromatin
- GO:0005794 Golgi apparatus
- GO:0016020 membrane
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0032991 protein-containing complex
- GO:0071889 14-3-3 protein binding
- GO:0051117 ATPase binding
- GO:0008013 beta-catenin binding
- GO:0005516 calmodulin binding
- GO:0003682 chromatin binding
- GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
- GO:0003700 DNA-binding transcription factor activity
- GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
- GO:0019899 enzyme binding
- GO:0034056 estrogen response element binding
- GO:0042802 identical protein binding
- GO:0030235 nitric-oxide synthase regulator activity
- GO:0030284 nuclear estrogen receptor activity
- GO:0030331 nuclear estrogen receptor binding
- GO:0004879 nuclear receptor activity
- GO:0019901 protein kinase binding
- GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
- GO:1990837 sequence-specific double-stranded DNA binding
- GO:0005496 steroid binding
- GO:0017025 TBP-class protein binding
- GO:0001093 TFIIB-class transcription factor binding
- GO:0001223 transcription coactivator binding
- GO:0001221 transcription coregulator binding
- GO:0001222 transcription corepressor binding
- GO:0008270 zinc ion binding
- GO:0071392 cellular response to estradiol stimulus
- GO:0071391 cellular response to estrogen stimulus
- GO:0006338 chromatin remodeling
- GO:0030520 estrogen receptor signaling pathway
- GO:0043124 negative regulation of canonical NF-kappaB signal transduction
- GO:0010629 negative regulation of gene expression
- GO:1902894 negative regulation of miRNA transcription
- GO:0034392 negative regulation of smooth muscle cell apoptotic process
- GO:0000122 negative regulation of transcription by RNA polymerase II
- GO:0030518 nuclear receptor-mediated steroid hormone signaling pathway
- GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway
- GO:0007204 positive regulation of cytosolic calcium ion concentration
- GO:0045893 positive regulation of DNA-templated transcription
- GO:0045429 positive regulation of nitric oxide biosynthetic process
- GO:0051000 positive regulation of nitric-oxide synthase activity
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0071168 protein localization to chromatin
- GO:0006355 regulation of DNA-templated transcription
- GO:0006357 regulation of transcription by RNA polymerase II
- GO:0032355 response to estradiol
- GO:0043627 response to estrogen
- GO:0051123 RNA polymerase II preinitiation complex assembly
- GO:0007165 signal transduction
- GO:0048863 stem cell differentiation
- GO:0043401 steroid hormone receptor signaling pathway
Disease associations
- estrogen resistance syndrome MONDO:0014148
Drugs targeting this protein · 42
- DIENESTROL agonist
- ESTRADIOL ACETATE agonist
- DIETHYLSTILBESTROL DIPHOSPHATE agonist
- TOREMIFENE CITRATE modulator
- ESTRADIOL CYPIONATE agonist
- ESTROPIPATE agonist
- MESTRANOL agonist
- QUINESTROL agonist
- ESTRADIOL agonist
- FULVESTRANT antagonist
- ESTRONE agonist
- CYCLOFENIL modulator
- ESTRADIOL VALERATE agonist
- ESTRIOL modulator
- OSPEMIFENE modulator
- BAZEDOXIFENE ACETATE modulator
- FISPEMIFENE modulator
- ARZOXIFENE modulator
- ALLYLESTRENOL agonist
- CLOMIPHENE CITRATE modulator
- LASOFOXIFENE modulator
- GTX-758 agonist
- TAS-108 antagonist
- MK-6913 agonist
- CHF4227 modulator
- BRILANESTRANT degrader
- DIETHYLSTILBESTROL agonist
- ELACESTRANT degrader
- AMCENESTRANT degrader
- ELACESTRANT HYDROCHLORIDE degrader
- GIREDESTRANT degrader
- CAMIZESTRANT degrader
- DROLOXIFENE modulator
- AFIMOXIFENE modulator
- LASOFOXIFENE TARTRATE modulator
- ESTETROL agonist
- IDOXIFENE modulator
- ACOLBIFENE modulator
- ETHINYL ESTRADIOL agonist
- TAMOXIFEN CITRATE modulator
- RALOXIFENE modulator
- ENCLOMIPHENE modulator
Related proteins · sequence + function similarity
- Estrogen receptor 0.99
- Estrogen receptor 0.99
- Estrogen receptor 0.99
- Estrogen receptor 0.98
- Estrogen receptor 0.98
- Estrogen receptor 0.98
- Estrogen receptor 0.97
- Estrogen receptor 0.93
- Estrogen receptor 0.93
- Estrogen receptor 0.91
- Estrogen receptor 0.91
- Estrogen receptor 0.90
Co-cited proteins · studied together in the literature
- Kinesin-like protein KIF18A 2 shared papers
- Nuclear receptor subfamily 2 group C member 1 1 shared papers
- Serine/threonine-protein kinase LMTK3 1 shared papers
- Pre-B-cell leukemia transcription factor-interacting protein 1 1 shared papers
- Swi5-dependent recombination DNA repair protein 1 homolog 1 shared papers
- SH2 domain-containing protein 4A 1 shared papers
- Estrogen receptor beta 7 shared papers
- RNA binding protein fox-1 homolog 2 1 shared papers
- Probable ATP-dependent RNA helicase DDX5 3 shared papers
- Coiled-coil domain-containing protein 62 1 shared papers
- CUE domain-containing protein 2 1 shared papers
- Estrogen receptor 1 shared papers
Literature · 111 cited papers
- UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability. Mol. Cell · 2023
- PMID 34718754 Nucleic Acids Res. · 2021
- The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERalpha. Nature · 2017
- Familial multiplicity of estrogen insensitivity associated with a loss-of-function ESR1 mutation. J. Clin. Endocrinol. Metab. · 2017
- Modification of ASC1 by UFM1 is crucial for ERalpha transactivation and breast cancer development. Mol. Cell · 2014
- PMID 24509260 Mol. Cell. Biol. · 2014
- JMJD6 regulates ERalpha methylation on arginine. PLoS ONE · 2014
- DNA homologous recombination factor SFR1 physically and functionally interacts with estrogen receptor alpha. PLoS ONE · 2013
- Delayed puberty and estrogen resistance in a woman with estrogen receptor alpha variant. N. Engl. J. Med. · 2013
- CLOCK is a substrate of SUMO and sumoylation of CLOCK upregulates the transcriptional activity of estrogen receptor-alpha. Oncogene · 2013
- CBP mediates NF-kappaB-dependent histone acetylation and estrogen receptor recruitment to an estrogen response element in the BIRC3 promoter. Mol. Cell. Biol. · 2012
- DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors. Mol. Biol. Cell · 2012
- … and 99 more in the literature graph