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 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, PELP1 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 ERS1-mediated transcription. Interacts with DNTTIP2, FAM120B and UIMC1. Interacts with isoform 4 of TXNRD1. Interacts with 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 DYX1C1. Interacts with PRMT2. Interacts with PI3KR1 or PI3KR2, SRC and PTK2. Interacts with RBFOX2.

SUBCELLULAR LOCATION: Isoform 1: Nucleus. Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note=A minor fraction is associated with the inner membrane.

SUBCELLULAR LOCATION: Isoform 3: Nucleus. Cytoplasm. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note=Associated with the inner membrane via palmitoylation (Probable).

ALTERNATIVE PRODUCTS: Event=Alternative promoter usage, Alternative splicing; Named isoforms=4; Name=1; Synonyms=Long, hER-alpha66, ER66; IsoId=P03372-1; Sequence=Displayed; Name=2; Synonyms=Short; IsoId=P03372-2; Sequence=VSP_003680; Name=3; Synonyms=hER-alpha46, ER46; IsoId=P03372-3; Sequence=VSP_041454, VSP_041456; Note=Found in the cytosol, in the nucleus and associated with the plasma membrane. May trigger membrane-initiated mitogenic estrogen signaling. Palmitoylated. Not biotinylated; Name=4; Synonyms=hER-alpha36, ER36; IsoId=P03372-4; Sequence=VSP_041454, VSP_041455; Note=Produced by alternative promoter usage;

DOMAIN: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

PTM: Phosphorylated by cyclin A/CDK2. Phosphorylation probably enhances transcriptional activity.

PTM: Glycosylated; contains N-acetylglucosamine, probably O- linked.

PTM: Ubiquitinated. Deubiquitinated by OTUB1.

PTM: Dimethylated by PRMT1 at Arg-260. The methylation may favor cytoplasmic localization.

PTM: Palmitoylated (isoform 3). Not biotinylated (isoform 3). 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, disrutption 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.

SIMILARITY: Belongs to the nuclear hormone receptor family. NR3 subfamily.

SIMILARITY: Contains 1 nuclear receptor DNA-binding domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/esr1/"; WEB RESOURCE: Name=Wikipedia; Note=Estrogen receptor entry; URL="http://en.wikipedia.org/wiki/Estrogen_receptor";

GENE SYNONYMS: ESR NR3A1.

COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.