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Symbol ESR1 contributors: mct - updated : 17-10-2018
HGNC name estrogen receptor 1
HGNC id 3467
Type widely
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Reproductivefemale systembreast  highly Homo sapiens
 female systemovary  highly Homo sapiens
 male systemprostate  highly
Urinarykidney   moderately
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadiposebrown highly Homo sapiensFetal
Muscularstriatumskeletal highly
SystemCellPubmedSpeciesStageRna symbol
cell lineage
cell lines
  • a N terminal modulator domain
  • a central bipartite zinc finger DNA binding domain
  • a nuclear localization signal (NLS)
  • a DNA binding domain required for high-affinity nuclear interaction induced by estradiol (Weinberg 2007)
  • a C terminal ligand binding domain, including a transactivation and dimerization domain, translocation of ESR1 from cell membrane to nucleus is mediated by MAP kinase and ligand independent
  • conjugated GlycoP , PhosphoP
    mono polymer homomer , heteromer , dimer
    interspecies homolog to murine Esr1 (89.6pc)
    homolog to rattus Esr1 (88.9pc)
  • nuclear hormone receptor family
  • NR3 subfamily
  • CATEGORY transcription factor , receptor nuclear
    SUBCELLULAR LOCALIZATION     plasma membrane
  • translocation of ESR1 from all membrane to nucleus is mediated by MAP kinase and ligand independent
  • under an unstimulated condition, resides in the cytoplasm; upon binding to its hormone ligands, such as 17beta-estradiol, ESR1 dimerize and translocates into the nucleus
  • basic FUNCTION
  • ligand-activated transcription factor involved in hormone-mediated inhibition of gene expression, by binding estrogen responsive element (ERE) or interacting with other transcription factors (like FOXA1)
  • playing an important role in mediating estrogen signaling and having an effect on menarcheal age
  • involved in the regulation of gene expression and affects cellular proliferation and differentiation
  • BARX2 and ESR1 may coordinately regulate cell growth, survival and invasion pathways that are critical to breast cancer progression
  • ESR1 is co-expressed with C6ORF211, spanning a breast cancer susceptibility locus
  • ESR1, ESR2 may differentially affect cellular oxidative stress through influencing the rate of beta-oxidation of fatty acids in breast cancer cells
  • cross-talk of distinct modifications in the hinge region of ESR1 plays an important role in fine tuning the functions of ESR1 at chromatin in hormone response
  • potential role for ESR1, ESR2 in fetal brown adipose tissue development, primarily via ESR1
  • possible role of both ESR1, ESR2 in mitochondriogenesis
  • CELLULAR PROCESS nucleotide, transcription, initiation
    signaling hormonal
    a component
  • heterodimerizing with ESR2
    DNA binding to estrogen responsive element (ERE)
    small molecule
  • PI3K
  • BARX2 and ESR1 proteins bind to different ESR1 gene promoters and regulate the expression of alternatively spliced mRNAs that encode 66 and 46 kDa ESR1 protein isoforms
  • SMYD3 functions as a coactivator of ESR1 and potentiates ESR1 activity in response to ligand
  • FLII can bind directly to both ESR1 and ACTL6A, an actin-related component of the SWI/SNF complex, suggesting that FLII may recruit SWI/SNF to ESR1 target genes via interaction with ACTL6A
  • NCOA2 interacts with ESR1, ESR2 and PGR in a subtype-specific manner, which may contribute to the functional differences of these steroid receptor subtypes in brain
  • interacts with corepressor complexes, which normally consist of histone deacetylases (HDACs), to remove acetylation on histones, leading to gene repression
  • estrogen induces the binding of the ESR1 onto the promoter of ZFHX3 and ZFHX3 is an ESR1 target gene
  • ESR1, ESR2 coordinate with MLL and MLL3 in E2-mediated transcriptional regulation of HOXB9
  • role of FLI1 as a negative regulator of the ESR1 gene in dermal fibroblasts
  • association of ESR1 and CRKL directly enhances the tumorigenic potential of CRKL, thus pointing to its role in cell proliferation
  • cooperation of KAT5 with ESR1 and other chromatin-remodeling enzymes is required for estrogen-induced transcription
  • KDM1A functions as a transcription coactivator of ESR1 and androgen receptor (AR)
  • by destabilizing ESR1, RUNX3 acts as a novel tumor suppressor in breast cancer
  • in breast cancer cells, NR5A2 promotes cell proliferation by enhancing ESR1 mediated transcription of target genes such as GREB1)
  • ESR1 interacts with both SAFB1 and SAFB2 in the presence of E2
  • TP53 is a target gene of ESR1 (feedback loop between ESR1 and TP53 and a biological role of TP53 in the DNA damage response in ER-positive breast cancers)
  • rapid, non-genomic changes in cardiac myofilament function following acute ESR1 stimulation mediated by the MAPK14 pathway
  • ESR1 interacted with mitochondrial protein HADHB and affected the thiolytic cleavage activity of HADHB in beta-oxidation
  • ESR1 regulation of its own mRNA expression is facilitated by RBCK1 recruitment, suggesting an ESR1 coactivator function of RBCK1
  • CACUL1 associated with histone demethylase KDM1A and suppressed KDM1A-enhanced ESR1 activity
  • LATS2 modulates ESR1-regulated gene transcription, through direct and/or indirect interactions with ESR1
  • HDAC3 is necessary for ESR1 mRNA stability, and is involved in the estrogen-dependent proliferation of ESR1-positive tumors
  • GRB1 is a chromatin-bound ESR1 coactivator and is essential for ESR1-mediated transcription, because it stabilizes interactions between ESR1 and additional cofactors
  • ESR1 coregulator PELP1 plays an important role in ESR1 signaling and is a proto-oncogene with aberrant expression in breast cancer
  • PELP1-CARM1 interactions synergistically enhance ESR1 transactivation
  • PDZK1 expression was indirectly regulated by ESR1 stimulation, requiring IGF1R expression and function
  • plays a crucial role in decreasing HIF1A protein levels in osteoclasts, even in hypoxic conditions (
  • PRL promotes pubertal ESR1-dependent mammary ductal elongation and gene expression in the absence of estrogen, which are abrogated by the antiestrogen
  • role for HOXA7 in modulating breast cancer cell proliferation via regulation of ESR1 expression
  • SMYD2 directly methylates estrogen receptor alpha (ESR1) protein at lysine 266 and represses ESR1 transactivation activity
  • SMYD2 attenuates ESR1 chromatin recruitment
  • KDM1A cooperates with EP300 to facilitate ESR1 protein acetylation and target gene activation upon estrogen stimulation
  • UBR5, a protein commonly amplified in breast cancer, is a novel regulator of ESR1 protein levels and transcriptional activity
  • is a new epigenetic regulator of ESR1 activity and cellular differentiation
  • ESR1 stimulates likely IBSP gene transcription in a ligand-independent manner by targeting the CRE and AP1/GRE elements in the IBSP gene promoter
  • interactions between FOXP1 and ESR1 may play a pivotal role in the progression of ovarian cancer
  • coupling between ESR1 and lipid raft CAV1 is critical for membrane ER signaling in synaptic plasticity and therefore, increased coupling of CAV1 and ESR1 may elucidate a critical abnormal mechanism of Fragile X syndrome (FRAXA)
  • PINX1 interacts with the N-terminal domain of ESR1 and functions as a corepressor of ESR1
  • ESR1 interacts with DLX3 and increases its transcriptional activity and DNA binding affinity
  • CCNE1/REL and TUBA1B/ESR1 might play pivotal roles in the occurrence and development of Postmenopausal osteoporosis
  • WBP2 acts as a transcriptional coactivator for ESR1 and progesterone receptor (PGR)
  • SRARP is an interacting partner of ESR1
  • crucial role of ESR1 for the mammalian female in regulating semen coagulation and liquefaction with KLK3
  • because methylation represses ESR1 activity, the observed complex formation between SMYD2 and HSP90AA1/PTGES3 may contribute to ESR1 regulation
  • SAFB and its paralogue, SAFB2, are nuclear matrix-binding proteins that negatively modulate ESR1-mediated transcription
  • binding of ESR1 is crucial for chromatin remodeling of NR5A1 enhancer and promoter, leading to RNA polymerase recruitment and transcription
  • TNPO2 regulates nucleocytoplasmic shuttling and cytoplasmic retention of ESR1, so that ESR1 has precise functions depending on the stimulation
  • likely ESR1 interacts with NFATC1 to repress WNT5B protein expression
  • cell & other
    activated by Ser164 phosphorylation through the RPS6KB1 and RPS6KA1 signaling pathways and may be a cuase of resistance to anti-estrogen therapy in breast cancer (Yamnick 2010)
    inhibited by BRCA1 (modulated by EP300)
    repressed by ZNF398
    actions of estrogen receptor alpha and SIN3A at the proximal promoter (Ellison-Zelski 2009)
    MAPK7/MAP2K5 signaling that suppresses ESR1 expression and promotes hormone-independent tumorigenesis
    Other coactivated by PPARBP
    coactivated by HRMT1L1
    direct binding to chromatin required the presence of Forkhead factor (FOXA1) binding in close proximity
    phosphorylated by cyclin A/CDK2, enhancing transcriptional activity
    deubiquitinated by OTUB1
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with TNFRSF6 in several cancer cell lines (prostate, breast, cervical bladder)
    tumoral     --low  
    by hypermethylation, methylation being both age-dependent and tumor differentiation-dependent, in late- stage prostate carcinoma
    tumoral   amplification    
    in proliferative breast disease and breast cancer
    constitutional       loss of function
    inactivation through methylation of TUSC3 and ESR1 associated with ulcerative colitis, but not with colrectal carcinoma
    tumoral   amplification    
    may be an early event in endometrial carcinoma development
  • several cancer cell lines (prostate, breast, cervical bladder)
  • to reduced hip bone mass density and to risk of femoral neck bone loss in postmenopausal women
  • to low lumbar bone mass density in postmenopausal women
  • to estrogenic effects of environmental endocrine disruptors in cryptorchidism
  • to risk of hypospadias
  • to type 2 diabetes patients with nephropathy
  • to idiopathic male infertility
  • to breast cancer
  • Variant & Polymorphism SNP , repeat , other
  • (TA)n repeat variant (short alleles)
  • haplotype px associated with reduced hip bone mass density and risk of femoral neck bone loss in postmenopausal women
  • G allele containing variants of ESR1 XbaI may decrease the risk of hypospadias, whereas the ESR1 C-A haplotype may increase its risk
  • homozygosity for the specific ESR1 haplotype in the development of cryptorchidism
  • SNP increasing the risk of type 2 diabetes patients with nephropathy
  • variant associated with idiopathic male infertility
  • SNP rs2046210 at 6q25.1, located upstream of ESR1, showed strong and consistent association with breast cancer across all three stages (Zheng 2009)
  • Candidate gene
    Therapy target
    role for therapeutic selective ESR1 modulation in the attenuation or prevention of toxic oligomeric Abeta species formation in ALzheimer and related disorders
  • osteoporotic phenotype of Esr1(-/NERKI) mice may involve the suppression of Lef1-mediated Wnt signaling through both the stimulation of secreted Wnt inhibitors and/or disruption of normal CTNNB function