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ESR2 (Estrogen Receptor 2 (ER beta))

Written2008-04Chunyan Zhao, Karin Dahlman-Wright, Jan-Ake Gustafsson
Department of Biosciences, Nutrition, Novum, Karolinska Institutet, S-141 57 Huddinge, Sweden

(Note : for Links provided by Atlas : click)


HGNC (Hugo) ESR2
HGNC Alias symbNR3A2
HGNC Alias nameER beta
 estrogen receptor beta
 oestrogen receptor beta
 nuclear receptor subfamily 3 group A member 2
HGNC Previous nameestrogen receptor 2 (ER beta)
LocusID (NCBI) 2100
Atlas_Id 40500
Location 14q23.2  [Link to chromosome band 14q23]
Location_base_pair Starts at 64233029 and ends at 64294410 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping ESR2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)


  Genomic organization of human ER beta gene, protein and functional domains.
Gene: exons are indicated with boxes and introns with lines. The numbers above each box indicate the size of the exons (bp); the numbers below each line designate the size of the respective introns (bp). Dotted lines between gene and protein point to protein domain junctions.
Protein: numbers indicate the total size of the protein in amino acids. The shaded bar shows the divergent C-terminal regions between the isoforms.
Description ER beta gene consists of 8 encoding exons. The open reading frame of the coding region is 1,593 bp.


Description The full-length human ER beta protein is 530 amino acids; 59.2 KDa, is also named ER beta1. Another isoform, ER beta2, is formed by alternative splicing of the mRNA. ER beta2 encodes a protein of 495 amino acid residues, with a molecular weight of 55.5 kDa. ER beta2 has a unique C-terminus, where the amino acids corresponding to exon 8 are replaced with 26 unique amino acids.
Expression ER beta is mainly expressed in tissues such as the ovary (granulosa cells), prostate (epithelium), testis, epididymis, colon, lung, bladder, bone marrow, salivary gland, vascular endothelium and regions of the brain, including hypothalamus and cortex.
Localisation Nucleus
Function Cellular signaling of estrogen is mediated through two estrogen receptors (ERs), ER alpha and ER beta. The first ER, now known as ER alpha, was cloned in 1986. This receptor was regarded as the only ER that mediates estrogenic effects, until a second ER, now known as ER beta, was cloned from rat prostate. ER alpha and ER beta belong to the superfamily of nuclear receptors and specifically to the family of steroid receptors that act as ligand-regulated transcription factors. ER alpha and ER beta have a high sequence homology and share affinity for the same ligands and DNA response elements.
Binding of ligand activates ERs, by a mechanism that involves dissociation of heat shock proteins and dimerization of receptor proteins. Estrogen-modulated gene transcription is exerted via different mechanisms: the genomic and the nongenomic pathways. The canonical model for ER-mediated regulation of gene expression involves the direct binding of dimeric ER to DNA sequences known as estrogen response elements (EREs), followed by recruitment of a variety of coregulators to alter chromatin structure and facilitate recruitment of the RNA polymerase II (Pol II) transcriptional machinery.
The transcriptional activity of ERs can be modulated by different types of post-translational modifications such as phosphorylation, acetylation, sumoylation, ubiquitination and methylation.
ER alpha and ER beta exhibit different affinities for some natural compounds, and distinct expression patterns in a variety of tissues. Transcriptional activation by ER alpha is mediated by two distinct activation functions: the constitutively active AF-1 and the ligand-dependent AF-2. ER beta seems to have a weaker corresponding AF-1 function and thus depends more on the AF-2 for its transcriptional activation function. ER alpha and ER beta have different activities in certain ligand, cell-type, and promoter contexts.
Homology Chimpanzee (Pan troglodytes), dog (Canis lupus familiaris), cow (Bos taurus), mouse (Mus musculus), rat (Rattus norvegicus) chicken (Gallus gallus), zebrafish (Danio rerio).

Implicated in

Entity Various cancers
Note Targeted disruption of ER beta in mice has suggested roles for ER beta in many tissues and organs, including the ovary, uterus, mammary gland, brain, immune system and ventral prostate.
Entity Prostate cancer
Disease Estrogens can have profound effects on prostate growth and differentiation as well as in the pathogenesis of prostate cancer. In the adult rodent ventral prostate, ER beta is expressed in the epithelial cells, whereas ER alpha is expressed in the stroma. The estrogenic effects in the prostate may therefore be exerted by both ERs but in different cells. ER beta knockout mice display signs of prostatic hyperplasia with aging.
Entity Breast cancer
Disease Estrogen is essential for growth and development of the mammary glands, and has been associated with promotion and growth of breast cancer. ER beta is found in both ductal and lobular epithelial and stromal cells of the rodent, whereas ER alpha is only found in the ductal and lobular epithelial cells and not in stroma. Recent studies have indicated a protective role of ER beta against breast cancer development. In vitro studies indicated that ER beta is an important modulator of proliferation and invasion of breast cancer cells.
Entity Colon cancer
Disease ER beta is the predominant ER in the colonic epithelium, suggesting that effects of estrogen in the colon are mediated by ER beta. In colons from ER beta knockout mice, the number of proliferating cells was higher, and the migration of labelled cells from base to lumen of the crypts was faster when compared to wild-type mice. Additionally, immunohistochemical staining revealed fewer apoptotic cells (cleaved caspase 3-positive), a significant decrease in expression of the epithelial differentiation marker, cytokeratin CK20, the adherens junction protein, alpha -catenin, and the hemidesmosomal protein, plectin, in ER beta knockout mice. These findings suggest a role for ER beta in the organization and architectural maintenance of the colon.
Entity Ovarian cancer
Disease A loss of ER beta expression or a decrease in ER beta/ER alpha ratio in epithelial ovarian cancer cells as compared with normal tissues has been reported by several groups. ER beta overexpression in ovarian cancer cells has been reported to exert antitumoral effects.


International Union of Pharmacology. LXIV. Estrogen receptors.
Dahlman-Wright K, Cavailles V, Fuqua SA, Jordan VC, Katzenellenbogen JA, Korach KS, Maggi A, Muramatsu M, Parker MG, Gustafsson JA.
Pharmacol Rev. 2006 Dec;58(4):773-81. (REVIEW
PMID 17132854
Estrogen receptor-beta: recent lessons from in vivo studies.
Harris HA.
Mol Endocrinol. 2007 Jan;21(1):1-13. (REVIEW)
PMID 16556737
Cloning of a novel receptor expressed in rat prostate and ovary.
Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA.
Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5925-30.
PMID 8650195
Mechanisms of estrogen action.
Nilsson S, Mäkelä S, Treuter E, Tujague M, Thomsen J, Andersson G, Enmark E, Pettersson K, Warner M, Gustafsson JA.
Physiol Rev. 2001 Oct;81(4):1535-65. (REVIEW)
PMID 11581496
Molecular cloning and characterization of human estrogen receptor betacx: a potential inhibitor ofestrogen action in human.
Ogawa S, Inoue S, Watanabe T, Orimo A, Hosoi T, Ouchi Y, Muramatsu M.
Nucleic Acids Res. 1998 Aug 1;26(15):3505-12.
PMID 9671811
Estrogen receptor beta: an overview and update.
Zhao C, Dahlman-Wright K, Gustafsson JA.
Nucl Recept Signal. 2008 Feb 1;6:e003. (REVIEW)
PMID 18301783


This paper should be referenced as such :
Zhao, C ; Dahlman-Wright, K ; Gustafsson, JA
ESR2 (Estrogen Receptor 2 (ER beta) )
Atlas Genet Cytogenet Oncol Haematol. 2009;13(3):201-203.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(3;21)(q26;q11) NRIP1::MECOM

External links

HGNC (Hugo)ESR2   3468
Entrez_Gene (NCBI)ESR2    estrogen receptor 2
Erb; NR3A2; ODG8
GeneCards (Weizmann)ESR2
Ensembl hg19 (Hinxton)ENSG00000140009 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000140009 [Gene_View]  ENSG00000140009 [Sequence]  chr14:64233029-64294410 [Contig_View]  ESR2 [Vega]
ICGC DataPortalENSG00000140009
TCGA cBioPortalESR2
AceView (NCBI)ESR2
Genatlas (Paris)ESR2
SOURCE (Princeton)ESR2
Genetics Home Reference (NIH)ESR2
Genomic and cartography
GoldenPath hg38 (UCSC)ESR2  -     chr14:64233029-64294410 -  14q23.2-q23.3   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)ESR2  -     14q23.2-q23.3   [Description]    (hg19-Feb_2009)
GoldenPathESR2 - 14q23.2-q23.3 [CytoView hg19]  ESR2 - 14q23.2-q23.3 [CytoView hg38]
Genome Data Viewer NCBIESR2 [Mapview hg19]  
OMIM601663   618187   
Gene and transcription
Genbank (Entrez)AB006589 AB006590 AB209620 AF047463 AF051427
RefSeq transcript (Entrez)NM_001040275 NM_001040276 NM_001214902 NM_001214903 NM_001271876 NM_001271877 NM_001291712 NM_001291723 NM_001437
Consensus coding sequences : CCDS (NCBI)ESR2
Gene ExpressionESR2 [ NCBI-GEO ]   ESR2 [ EBI - ARRAY_EXPRESS ]   ESR2 [ SEEK ]   ESR2 [ MEM ]
Gene Expression Viewer (FireBrowse)ESR2 [ Firebrowse - Broad ]
GenevisibleExpression of ESR2 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)2100
GTEX Portal (Tissue expression)ESR2
Human Protein AtlasENSG00000140009-ESR2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)ESR2
Human Protein Atlas [tissue]ENSG00000140009-ESR2 [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:17:25 CEST 2021

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