Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

ESR2 (Estrogen Receptor 2 (ER beta))

Identity

Other namesESRB
ESR-BETA
ESTRB
ER-BETA
Erb
NR3A2
HGNC (Hugo) ESR2
LocusID (NCBI) 2100
Location 14q23.2
Location_base_pair Starts at 64693751 and ends at 64761128 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

 
  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.

Protein

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.
  

External links

Nomenclature
HGNC (Hugo)ESR2   3468
Cards
AtlasESR2ID40500ch14q23
Entrez_Gene (NCBI)ESR2  2100  estrogen receptor 2 (ER beta)
GeneCards (Weizmann)ESR2
Ensembl (Hinxton)ENSG00000140009 [Gene_View]  chr14:64693751-64761128 [Contig_View]  ESR2 [Vega]
ICGC DataPortalENSG00000140009
cBioPortalESR2
AceView (NCBI)ESR2
Genatlas (Paris)ESR2
WikiGenes2100
SOURCE (Princeton)NM_001040275 NM_001040276 NM_001214902 NM_001214903 NM_001271876 NM_001271877 NM_001291712 NM_001291723 NM_001437
Genomic and cartography
GoldenPath (UCSC)ESR2  -  14q23.2   chr14:64693751-64761128 -  14q23.2   [Description]    (hg19-Feb_2009)
EnsemblESR2 - 14q23.2 [CytoView]
Mapping of homologs : NCBIESR2 [Mapview]
OMIM601663   
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
RefSeq genomic (Entrez)AC_000146 NC_000014 NC_018925 NG_011535 NT_026437 NW_001838111 NW_004929393
Consensus coding sequences : CCDS (NCBI)ESR2
Cluster EST : UnigeneHs.734416 [ NCBI ]
CGAP (NCI)Hs.734416
Alternative Splicing : Fast-db (Paris)GSHG0009421
Alternative Splicing GalleryENSG00000140009
Gene ExpressionESR2 [ NCBI-GEO ]     ESR2 [ SEEK ]   ESR2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ92731 (Uniprot)
NextProtQ92731  [Medical]
With graphics : InterProQ92731
Splice isoforms : SwissVarQ92731 (Swissvar)
Domaine pattern : Prosite (Expaxy)NUCLEAR_REC_DBD_1 (PS00031)    NUCLEAR_REC_DBD_2 (PS51030)   
Domains : Interpro (EBI)ER-beta/gamma [organisation]   Estrogen_rcpt_beta_N [organisation]   Nucl_hormone_rcpt_ligand-bd [organisation]   Nucl_hrmn_rcpt_lig-bd_core [organisation]   Oest_rcpt/oest-rel_rcp [organisation]   Str_hrmn_rcpt [organisation]   Znf_hrmn_rcpt [organisation]   Znf_NHR/GATA [organisation]  
Related proteins : CluSTrQ92731
Domain families : Pfam (Sanger)ERbeta_N (PF12497)    Hormone_recep (PF00104)    zf-C4 (PF00105)   
Domain families : Pfam (NCBI)pfam12497    pfam00104    pfam00105   
Domain families : Smart (EMBL)HOLI (SM00430)  ZnF_C4 (SM00399)  
DMDM Disease mutations2100
Blocks (Seattle)Q92731
PDB (SRS)1L2J    1NDE    1QKM    1U3Q    1U3R    1U3S    1U9E    1X76    1X78    1X7B    1X7J    1YY4    1YYE    1ZAF    2FSZ    2GIU    2I0G    2JJ3    2NV7    2QTU    2YJD    2YLY    2Z4B    3OLL    3OLS    3OMO    3OMP    3OMQ    4J24    4J26   
PDB (PDBSum)1L2J    1NDE    1QKM    1U3Q    1U3R    1U3S    1U9E    1X76    1X78    1X7B    1X7J    1YY4    1YYE    1ZAF    2FSZ    2GIU    2I0G    2JJ3    2NV7    2QTU    2YJD    2YLY    2Z4B    3OLL    3OLS    3OMO    3OMP    3OMQ    4J24    4J26   
PDB (IMB)1L2J    1NDE    1QKM    1U3Q    1U3R    1U3S    1U9E    1X76    1X78    1X7B    1X7J    1YY4    1YYE    1ZAF    2FSZ    2GIU    2I0G    2JJ3    2NV7    2QTU    2YJD    2YLY    2Z4B    3OLL    3OLS    3OMO    3OMP    3OMQ    4J24    4J26   
PDB (RSDB)1L2J    1NDE    1QKM    1U3Q    1U3R    1U3S    1U9E    1X76    1X78    1X7B    1X7J    1YY4    1YYE    1ZAF    2FSZ    2GIU    2I0G    2JJ3    2NV7    2QTU    2YJD    2YLY    2Z4B    3OLL    3OLS    3OMO    3OMP    3OMQ    4J24    4J26   
Human Protein AtlasENSG00000140009 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ92731
HPRD03390
IPIIPI00023212   IPI00218153   IPI00397583   IPI00218155   IPI00218156   IPI00218157   IPI00218158   IPI01019014   IPI00384140   IPI01024780   IPI00218159   
Protein Interaction databases
DIP (DOE-UCLA)Q92731
IntAct (EBI)Q92731
FunCoupENSG00000140009
BioGRIDESR2
InParanoidQ92731
Interologous Interaction database Q92731
IntegromeDBESR2
STRING (EMBL)ESR2
Ontologies - Pathways
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  core promoter sequence-specific DNA binding  ovarian follicle development  neuron migration  DNA binding  sequence-specific DNA binding transcription factor activity  steroid hormone receptor activity  transcription coactivator activity  ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity  ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity  steroid binding  steroid binding  protein binding  extracellular region  nucleus  nucleus  nucleoplasm  mitochondrion  regulation of transcription, DNA-templated  transcription initiation from RNA polymerase II promoter  signal transduction  cell-cell signaling  brain development  zinc ion binding  hormone-mediated apoptotic signaling pathway  gene expression  enzyme binding  estrogen receptor activity  negative regulation of cell growth  intracellular estrogen receptor signaling pathway  estrogen response element binding  steroid hormone mediated signaling pathway  receptor antagonist activity  negative regulation of epithelial cell proliferation  positive regulation of sequence-specific DNA binding transcription factor activity  uterus development  vagina development  prostate gland epithelium morphogenesis  epithelial cell maturation involved in prostate gland development  negative regulation of androgen receptor signaling pathway  extracellular negative regulation of signal transduction  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  core promoter sequence-specific DNA binding  ovarian follicle development  neuron migration  DNA binding  sequence-specific DNA binding transcription factor activity  steroid hormone receptor activity  transcription coactivator activity  ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity  ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity  steroid binding  steroid binding  protein binding  extracellular region  nucleus  nucleus  nucleoplasm  mitochondrion  regulation of transcription, DNA-templated  transcription initiation from RNA polymerase II promoter  signal transduction  cell-cell signaling  brain development  zinc ion binding  hormone-mediated apoptotic signaling pathway  gene expression  enzyme binding  estrogen receptor activity  negative regulation of cell growth  intracellular estrogen receptor signaling pathway  estrogen response element binding  steroid hormone mediated signaling pathway  receptor antagonist activity  negative regulation of epithelial cell proliferation  positive regulation of sequence-specific DNA binding transcription factor activity  uterus development  vagina development  prostate gland epithelium morphogenesis  epithelial cell maturation involved in prostate gland development  negative regulation of androgen receptor signaling pathway  extracellular negative regulation of signal transduction  
Pathways : KEGGEstrogen signaling pathway    Prolactin signaling pathway   
Protein Interaction DatabaseESR2
Wikipedia pathwaysESR2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)ESR2
snp3D : Map Gene to Disease2100
SNP (GeneSNP Utah)ESR2
SNP : HGBaseESR2
Genetic variants : HAPMAPESR2
Exome VariantESR2
1000_GenomesESR2 
ICGC programENSG00000140009 
Somatic Mutations in Cancer : COSMICESR2 
CONAN: Copy Number AnalysisESR2 
Mutations and Diseases : HGMDESR2
Genomic VariantsESR2  ESR2 [DGVbeta]
dbVarESR2
ClinVarESR2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM601663   
MedgenESR2
GENETestsESR2
Disease Genetic AssociationESR2
Huge Navigator ESR2 [HugePedia]  ESR2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneESR2
Homology/Alignments : Family Browser (UCSC)ESR2
Phylogenetic Trees/Animal Genes : TreeFamESR2
Chemical/Protein Interactions : CTD2100
Chemical/Pharm GKB GenePA27886
Clinical trialESR2
Cancer Resource (Charite)ENSG00000140009
Other databases
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineESR2
iHOPESR2
OncoSearchESR2

Bibliography

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
 
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
 
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
 
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
 
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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written04-2008Chunyan Zhao, Karin Dahlman-Wright, Jan-Ake Gustafsson
Department of Biosciences and Nutrition, Novum, Karolinska Institutet, S-141 57 Huddinge, Sweden

Citation

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 online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/ESR2ID40500ch14q23.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Jul 26 15:18:53 CEST 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.