ESR1

Gene Information
 
Gene Symbol
ESR1
 
Aliases
ER, ESR, ESRA, ESTRR, Era, NR3A1
 
Entrez Gene ID
 
Gene Name
Estrogen receptor 1
 
Chromosomal Location
6q25.1-q25.2
 
HGNC ID
 
Summary
This gene encodes an estrogen receptor and ligand-activated transcription factor. The canonical protein contains an N-terminal ligand-independent transactivation domain, a central DNA binding domain, a hinge domain, and a C-terminal ligand-dependent transactivation domain. The protein localizes to the nucleus where it may form either a homodimer or a heterodimer with estrogen receptor 2. The protein encoded by this gene regulates the transcription of many estrogen-inducible genes that play a role in growth, metabolism, sexual development, gestation, and other reproductive functions and is expressed in many non-reproductive tissues. The receptor encoded by this gene plays a key role in breast cancer, endometrial cancer, and osteoporosis. This gene is reported to have dozens of transcript variants due to the use of alternate promoters and alternative splicing, however, the full-length nature of many of these variants remain uncertain. [provided by RefSeq, Jul 2020]
 
RefSeq DNA
 
RefSeq mRNA
  e!Ensembl
Gene
Transcript  
Protein

SNPs

SNP
SNP ID
Associated disease
References
p.G145S
Central Precocious Puberty (CPP)

Gene Ontology (GO)

GO ID Ontology Function Evidence Reference
GO:0000122 Biological process Negative regulation of transcription by RNA polymerase II IMP 20388878
GO:0006338 Biological process Chromatin remodeling NAS 12351687
GO:0006355 Biological process Regulation of transcription, DNA-templated NAS 3753802
GO:0007165 Biological process Signal transduction TAS 10749889, 10970861
GO:0010629 Biological process Negative regulation of gene expression IDA 21695196
Protein Information
 
Protein Name
Estrogen receptor, E2 receptor alpha, ER-alpha, estradiol receptor, estrogen nuclear receptor alpha, estrogen receptor alpha E1-E2-1-2, estrogen receptor alpha E1-N2-E2-1-2, nuclear receptor subfamily 3 group A member 1, oestrogen receptor alpha
 
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. 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.
 
Refseq Proteins
 
UniProt
 
PDB
Pathways
 
KEGG
 
Reactome
 

Endocrine resistance
Estrogen signaling pathway
Prolactin signaling pathway
Thyroid hormone signaling pathway
Endocrine and other factor-regulated calcium reabsorption
Pathways in cancer
Proteoglycans in cancer
Breast cancer

 

Nuclear signaling by ERBB4
PIP3 activates AKT signaling
Constitutive Signaling by Aberrant PI3K in Cancer
Nuclear Receptor transcription pathway
SUMOylation of intracellular receptors
Ovarian tumor domain proteases
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
RUNX1 regulates estrogen receptor mediated transcription
ESR-mediated signaling
RUNX1 regulates transcription of genes involved in WNT signaling
Regulation of RUNX2 expression and activity
Extra-nuclear estrogen signaling
Estrogen-dependent gene expression

     
References
 
 
PubMed ID Disease SNP/Mutation Study population Ethnicity Age of study population Type of sample
Central Precocious Puberty (CPP) 
p.G145S  
Test Subjects- Girls: 204; Controls- Girls: 102 
Korean 
 
Blood

| © 2020, Biomedical Informatics Centre, NIRRH |
ICMR-National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai-400 012
Tel: 91-22-24192104, Fax No: 91-22-24139412