ER-alpha a widely expressed.nuclear estrogen receptor and transcription factor. Regulates eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. 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. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Belongs to the nuclear hormone receptor family, NR3 subfamily. Four human isoforms, two each from alternative promoters and alternative splicing have been reported. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full-length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1. Isoform 3 is not expressed in the pituitary gland. Isoform 3 is not expressed in the pituitary gland. Note: This description may include information from UniProtKB.
Protein type: DNA-binding; Nuclear receptor; Transcription factor
Chromosomal Location of mouse Ortholog: 10 A1|10 2.03 cM
Cellular Component:  chromatin; cytoplasm; euchromatin; Golgi apparatus; membrane; mitochondrion; neuron projection; nucleus; perikaryon; perinuclear region of cytoplasm; plasma membrane; protein-containing complex; T-tubule; terminal bouton; transcription preinitiation complex; transcription regulator complex
Molecular Function:  ATPase binding; beta-catenin binding; chromatin binding; DNA binding; DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription factor activity; enzyme binding; estrogen response element binding; hormone binding; identical protein binding; lipid binding; metal ion binding; nuclear estrogen receptor activity; nuclear estrogen receptor binding; nuclear receptor activity; nuclear steroid receptor activity; nucleic acid binding; phosphatidylinositol 3-kinase regulatory subunit binding; promoter-specific chromatin binding; protein binding; protein kinase binding; protein-containing complex binding; RNA polymerase II cis-regulatory region sequence-specific DNA binding; sequence-specific DNA binding; sequence-specific double-stranded DNA binding; steroid binding; TBP-class protein binding; TFIIB-class transcription factor binding; transcription coactivator binding; transcription coregulator binding; transcription corepressor binding; transcription factor binding; type 1 metabotropic glutamate receptor binding; zinc ion binding
Biological Process:  androgen metabolic process; antral ovarian follicle growth; cellular response to estradiol stimulus; cellular response to estrogen stimulus; epithelial cell development; epithelial cell proliferation involved in mammary gland duct elongation; fibroblast proliferation; intracellular estrogen receptor signaling pathway; intracellular steroid hormone receptor signaling pathway; male gonad development; mammary gland alveolus development; mammary gland branching involved in pregnancy; negative regulation of DNA-binding transcription factor activity; negative regulation of gene expression; negative regulation of glucose import; negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of miRNA maturation; negative regulation of mitotic nuclear division; negative regulation of neuron death; negative regulation of smooth muscle cell proliferation; negative regulation of transcription by RNA polymerase II; negative regulation of triglyceride metabolic process; phospholipase C-activating G protein-coupled receptor signaling pathway; positive regulation of cytosolic calcium ion concentration; positive regulation of DNA-binding transcription factor activity; positive regulation of DNA-templated transcription; positive regulation of epidermal growth factor receptor signaling pathway; positive regulation of epithelial cell proliferation; positive regulation of ERK1 and ERK2 cascade; positive regulation of fibroblast proliferation; positive regulation of nitric oxide biosynthetic process; positive regulation of nitric-oxide synthase activity; positive regulation of phospholipase C activity; positive regulation of RNA polymerase II transcription preinitiation complex assembly; positive regulation of transcription by RNA polymerase II; prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis; prostate epithelial cord elongation; protein localization to chromatin; regulation of branching involved in prostate gland morphogenesis; regulation of DNA-templated transcription; regulation of epithelial cell apoptotic process; regulation of inflammatory response; regulation of neuron apoptotic process; regulation of toll-like receptor signaling pathway; regulation of transcription by RNA polymerase II; response to estradiol; response to estrogen; Sertoli cell proliferation; stem cell differentiation; steroid hormone mediated signaling pathway; transcription by RNA polymerase II; uterus development; vagina development
Reference #:  P19785 (UniProtKB)
Alt. Names/Synonyms: AA420328; AU041214; C-terminally-truncated estrogen receptor alpha product-4; C-terminally-truncated estrogen receptor alpha product-5; C-terminally-truncated estrogen receptor alpha product-6; C-terminally-truncated estrogen receptor alpha product-7; ER; ER-; ER-alpha; ER[; ER[a]; ERa; ERalpha; Esr; Esr1; Estr; Estra; Estradiol receptor; Estrogen receptor; estrogen receptor 1 (alpha); estrogen receptor alpha variant U1; estrogen receptor alpha variant U2; Nr3a1; Nuclear receptor subfamily 3 group A member 1; OTTMUSP00000022868; OTTMUSP00000022869; OTTMUSP00000022870
Gene Symbols: Esr1
Molecular weight: 66,955 Da
Basal Isoelectric point: 8.3  Predict pI for various phosphorylation states
CST Pathways:  Growth And Differentiation Control by MAPKs
Select Structure to View Below


Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  Pfam  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene  |  NURSA