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33670_at
8122840
8122843
A_14_P136162
A_23_P309739
A_24_P325215
A_24_P383478
A_33_P3379356
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 (PubMed:17922032).SUBUNIT Binds DNA as a homodimer. Can form a heterodimer with ESR2. Interacts with FOXC2, MAP1S, SLC30A9, UBE1C and NCOA3 coactivator (By similarity). Interacts with PELP1, the interaction is enhanced by 17-beta-estradiol, the interaction increases ESR1 transcriptional activity (PubMed:11481323, PubMed:14963108). Interacts with EP300; the interaction is estrogen-dependent and enhanced by CITED1. Interacts with CITED1; the interaction is estrogen-dependent. Interacts with NCOA5 and NCOA6 coactivators. Interacts with NCOA7; the interaction is a ligand-inducible. Interacts with PHB2, and UBE1C. Interacts with AKAP13. Interacts with CUEDC2. Interacts with KDM5A. Interacts with SMARD1. Interacts with HEXIM1. Interacts with PBXIP1. Interaction with MUC1 is stimulated by 7 beta-estradiol (E2) and enhances ESR1-mediated transcription. Interacts with DNTTIP2, FAM120B and UIMC1. Interacts with isoform 4 of TXNRD1. Interacts with KMT2D/MLL2. Interacts with ATAD2 and this interaction is enhanced by estradiol. Interacts with KIF18A and LDB1. Interacts with RLIM (via C-terminus). Interacts with MACROD1. Interacts with SH2D4A and PLCG. Interaction with SH2D4A blocks binding to PLCG and inhibits estrogen-induced cell proliferation. Interacts with DYNLL1. Interacts with CCDC62 in the presence of estradiol/E2; this interaction seems 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 DNAAF4. Interacts with PRMT2. Interacts with RBFOX2. Interacts with STK3/MST2 only in the presence of SAV1 and vice-versa. Binds to CSNK1D. Interacts with NCOA2; NCOA2 can interact with ESR1 AF-1 and AF-2 domains simultaneously and mediate their transcriptional synergy. Interacts with DDX5 (PubMed:11682626). 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. Interacts with CLOCK and the interaction is stimulated by estrogen. Interacts with BCAS3. Interacts with TRIP4 (ufmylated); estrogen dependent. Interacts with LMTK3; the interaction phosphorylates ESR1 (in vitro) and protects it against proteasomal degradation. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts with ZFHX3. Interacts with SFR1 in a ligand-dependent and -independent manner (PubMed:23874500). Interacts with DCAF13, LATS1 and DCAF1; regulates ESR1 ubiquitination and ubiquitin-mediated proteasomal degradation (PubMed:28068668). Interacts (via DNA-binding domain) with POU4F2 (C-terminus); this interaction increases the estrogen receptor ESR1 transcriptional activity in a DNA- and ligand 17-beta-estradiol-independent manner (By similarity). Interacts with ESRRB isoform 1 (PubMed:19755138). Interacts with UBE3A and WBP2 (PubMed:16772533). Interacts with GTF2B (PubMed:1517211). Interacts with RBM39 (By similarity). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863). Interacts with PI3KR1 or PI3KR2 and PTK2/FAK1 (PubMed:18657504). Interacts with SRC (PubMed:14963108, PubMed:18657504).TISSUE SPECIFICITY Widely expressed (PubMed:10970861). Not expressed in the pituitary gland (PubMed:10970861).DOMAIN 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. AF-1 seems to provide the major transactivation function in differentiated cells.PTM Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably enhances transcriptional activity. Self-association induces phosphorylation. Dephosphorylation at Ser-118 by PPP5C inhibits its transactivation activity. Phosphorylated by LMTK3 in vitro.PTM Glycosylated; contains N-acetylglucosamine, probably O-linked.PTM Ubiquitinated; regulated by LATS1 via DCAF1 it leads to ESR1 proteasomal degradation (PubMed:21602804, PubMed:28068668). Deubiquitinated by OTUB1 (PubMed:19383985).PTM Dimethylated by PRMT1 at Arg-260. The methylation may favor cytoplasmic localization (PubMed:18657504, PubMed:24498420). Demethylated by JMJD6 at Arg-260 (PubMed:24498420).PTM Palmitoylated (isoform 3). Not biotinylated (isoform 3).PTM Palmitoylated 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.POLYMORPHISM Genetic variations in ESR1 are correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disruption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.MISCELLANEOUS Selective estrogen receptor modulators (SERMs), such as tamoxifen, raloxifene, toremifene, lasofoxifene, clomifene, femarelle and ormeloxifene, have tissue selective agonistic and antagonistic effects on the estrogen receptor (ER). They interfere with the ER association with coactivators or corepressors, mainly involving the AF-2 domain.SIMILARITY Belongs to the nuclear hormone receptor family. NR3 subfamily.CAUTION Was reported to be activated by DDX5. However, this study has been retracted due to concerns of image manipulation.
GE59651
GO:0000003
GO:0000122
GO:0000785
GO:0000978
GO:0000981
GO:0001093
GO:0001223
GO:0001226
GO:0001228
GO:0001547
GO:0002064
GO:0003674
GO:0003677
GO:0003682
GO:0003700
GO:0003707
GO:0004879
GO:0005496
GO:0005515
GO:0005575
GO:0005622
GO:0005634
GO:0005654
GO:0005694
GO:0005737
GO:0005794
GO:0005829
GO:0005886
GO:0006338
GO:0006355
GO:0006357
GO:0006367
GO:0006464
GO:0006629
GO:0006950
GO:0007165
GO:0007200
GO:0007204
GO:0007267
GO:0008013
GO:0008134
GO:0008150
GO:0008209
GO:0008219
GO:0008270
GO:0008283
GO:0008289
GO:0008584
GO:0009058
GO:0010629
GO:0010863
GO:0016020
GO:0016021
GO:0016579
GO:0017025
GO:0019899
GO:0019901
GO:0022607
GO:0030111
GO:0030154
GO:0030234
GO:0030235
GO:0030284
GO:0030331
GO:0030518
GO:0030520
GO:0030522
GO:0032355
GO:0032991
GO:0033146
GO:0034056
GO:0034121
GO:0034641
GO:0035327
GO:0040007
GO:0042592
GO:0042802
GO:0042981
GO:0043124
GO:0043167
GO:0043226
GO:0043401
GO:0043433
GO:0043565
GO:0043627
GO:0045893
GO:0045899
GO:0045944
GO:0046872
GO:0048146
GO:0048856
GO:0048863
GO:0050727
GO:0051091
GO:0051117
GO:0051276
GO:0051897
GO:0060065
GO:0060068
GO:0060523
GO:0060527
GO:0060687
GO:0060745
GO:0060749
GO:0060750
GO:0065003
GO:0071168
GO:0071391
GO:0071392
GO:0097550
GO:1903799
GO:1990837
HMNXSV003001759
Hs.247938.0.S1_3p_at
Hs.247976.0.S1_3p_s_at
ILMN_1678535
TC06001104.hg
TC06003132.hg
TC06003133.hg
X03635_at
X86816_at
g11907834_3p_a_at
g4503602_3p_at
![ER alpha36 [cytosol] icon](/icon/R-ICO-013644.svg){kind=icon}
