| 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). |
| Note | |
| 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 |
| |
| Nomenclature |
|---|
| HGNC (Hugo) | ESR2 3468 |
| Cards |
|---|
| Atlas | ESR2ID40500ch14q23 |
| Entrez_Gene (NCBI) | ESR2 2100 estrogen receptor 2 |
| Aliases | ER-BETA; ESR-BETA; ESRB; ESTRB; |
| Erb; NR3A2 |
| GeneCards (Weizmann) | ESR2 |
| Ensembl hg19 (Hinxton) | ENSG00000140009 [Gene_View] chr14:64693751-64761128 [Contig_View] ESR2 [Vega] |
| Ensembl hg38 (Hinxton) | ENSG00000140009 [Gene_View] chr14:64693751-64761128 [Contig_View] ESR2 [Vega] |
| ICGC DataPortal | ENSG00000140009 |
| TCGA cBioPortal | ESR2 |
| AceView (NCBI) | ESR2 |
| Genatlas (Paris) | ESR2 |
| WikiGenes | 2100 |
| SOURCE (Princeton) | ESR2 |
| Genomic and cartography |
|---|
| GoldenPath hg19 (UCSC) | ESR2 - chr14:64693751-64761128 - 14q23.2 [Description] (hg19-Feb_2009) |
| GoldenPath hg38 (UCSC) | ESR2 - 14q23.2 [Description] (hg38-Dec_2013) |
| Ensembl | ESR2 - 14q23.2 [CytoView hg19] ESR2 - 14q23.2 [CytoView hg38] |
| Mapping of homologs : NCBI | ESR2 [Mapview hg19] ESR2 [Mapview hg38] |
| OMIM | 601663 |
| 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) | NC_000014 NC_018925 NG_011535 NT_026437 NW_004929393 |
| Consensus coding sequences : CCDS (NCBI) | ESR2 |
| Cluster EST : Unigene | Hs.734416 [ NCBI ] |
| CGAP (NCI) | Hs.734416 |
| Alternative Splicing Gallery | ENSG00000140009 |
| Gene Expression | ESR2 [ NCBI-GEO ] ESR2 [ EBI - ARRAY_EXPRESS ]
ESR2 [ SEEK ] ESR2 [ MEM ] |
| Gene Expression Viewer (FireBrowse) | ESR2 [ Firebrowse - Broad ] |
| SOURCE (Princeton) | Expression in : [Datasets] [Normal Tissue Atlas] [carcinoma Classsification] [NCI60] |
| Genevisible | Expression in : [tissues] [cell-lines] [cancer] [perturbations] |
| BioGPS (Tissue expression) | 2100 |
| GTEX Portal (Tissue expression) | ESR2 |
| Protein : pattern, domain, 3D structure |
|---|
| UniProt/SwissProt | Q92731 (Uniprot) |
| NextProt | Q92731 [Sequence] [Exons] [Medical] [Publications] |
| With graphics : InterPro | Q92731 |
| Splice isoforms : SwissVar | Q92731 (Swissvar) |
| PhosPhoSitePlus | Q92731 |
| Domaine pattern : Prosite (Expaxy) | NUCLEAR_REC_DBD_1 (PS00031) NUCLEAR_REC_DBD_2 (PS51030) |
| Domains : Interpro (EBI) | ER-beta/gamma Estrogen_rcpt_beta_N Nucl_hrmn_rcpt_lig-bd Nuclear_hrmn_rcpt Oest_rcpt/oest-rel_rcp Znf_hrmn_rcpt Znf_NHR/GATA |
| 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 mutations | 2100 |
| Blocks (Seattle) | ESR2 |
| 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 |
| Structural Biology KnowledgeBase | 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 |
| SCOP (Structural Classification of Proteins) | 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 |
| CATH (Classification of proteins structures) | 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 |
| Superfamily | Q92731 |
| Human Protein Atlas | ENSG00000140009 |
| Peptide Atlas | Q92731 |
| HPRD | 03390 |
| IPI | IPI00023212 IPI00218153 IPI00397583 IPI00218155 IPI00218156 IPI00218157 IPI00218158 IPI01019014 IPI00384140 IPI01024780 IPI00218159 |
| Protein Interaction databases |
|---|
| DIP (DOE-UCLA) | Q92731 |
| IntAct (EBI) | Q92731 |
| FunCoup | ENSG00000140009 |
| BioGRID | ESR2 |
| STRING (EMBL) | ESR2 |
| ZODIAC | ESR2 |
| Ontologies - Pathways |
|---|
| QuickGO | Q92731 |
| Ontology : AmiGO | negative regulation of transcription from RNA polymerase II promoter core promoter sequence-specific DNA binding ovarian follicle development behavioral fear response DNA binding transcription factor activity, sequence-specific DNA binding steroid hormone receptor activity transcription coactivator activity RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding steroid binding steroid binding protein binding extracellular region nucleus nucleus nucleoplasm mitochondrion plasma membrane cilium regulation of transcription, DNA-templated transcription initiation from RNA polymerase II promoter signal transduction cell-cell signaling learning or memory drug binding zinc ion binding response to water deprivation response to activity response to insecticide enzyme binding cerebellum development amygdala development hypothalamus development estrogen receptor activity negative regulation of cell growth intracellular estrogen receptor signaling pathway prostate gland development response to nutrient levels protein-DNA complex response to testosterone response to genistein estrogen response element binding cellular response to drug RNA polymerase II transcription factor activity, estrogen-activated sequence-specific DNA binding peroxisome proliferator activated receptor binding neuron projection positive regulation of apoptotic process perikaryon regulation of neuron apoptotic process response to human chorionic gonadotropin estrous cycle response to ethanol positive regulation of epidermal growth factor receptor signaling pathway positive regulation of transcription, DNA-templated positive regulation of vasodilation positive regulation of transcription from RNA polymerase II promoter receptor antagonist activity perinuclear region of cytoplasm negative regulation of smooth muscle cell proliferation negative regulation of epithelial cell proliferation positive regulation of sequence-specific DNA binding transcription factor activity Sertoli cell development Sertoli cell proliferation positive regulation of ERK1 and ERK2 cascade cellular response to magnetism cellular response to estradiol stimulus response to dexamethasone extracellular negative regulation of signal transduction negative regulation of neuron death response to salt estradiol binding response to bisphenol A steroid hormone binding negative regulation of feeding behavior negative regulation of reactive oxygen species metabolic process |
| Ontology : EGO-EBI | negative regulation of transcription from RNA polymerase II promoter core promoter sequence-specific DNA binding ovarian follicle development behavioral fear response DNA binding transcription factor activity, sequence-specific DNA binding steroid hormone receptor activity transcription coactivator activity RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding steroid binding steroid binding protein binding extracellular region nucleus nucleus nucleoplasm mitochondrion plasma membrane cilium regulation of transcription, DNA-templated transcription initiation from RNA polymerase II promoter signal transduction cell-cell signaling learning or memory drug binding zinc ion binding response to water deprivation response to activity response to insecticide enzyme binding cerebellum development amygdala development hypothalamus development estrogen receptor activity negative regulation of cell growth intracellular estrogen receptor signaling pathway prostate gland development response to nutrient levels protein-DNA complex response to testosterone response to genistein estrogen response element binding cellular response to drug RNA polymerase II transcription factor activity, estrogen-activated sequence-specific DNA binding peroxisome proliferator activated receptor binding neuron projection positive regulation of apoptotic process perikaryon regulation of neuron apoptotic process response to human chorionic gonadotropin estrous cycle response to ethanol positive regulation of epidermal growth factor receptor signaling pathway positive regulation of transcription, DNA-templated positive regulation of vasodilation positive regulation of transcription from RNA polymerase II promoter receptor antagonist activity perinuclear region of cytoplasm negative regulation of smooth muscle cell proliferation negative regulation of epithelial cell proliferation positive regulation of sequence-specific DNA binding transcription factor activity Sertoli cell development Sertoli cell proliferation positive regulation of ERK1 and ERK2 cascade cellular response to magnetism cellular response to estradiol stimulus response to dexamethasone extracellular negative regulation of signal transduction negative regulation of neuron death response to salt estradiol binding response to bisphenol A steroid hormone binding negative regulation of feeding behavior negative regulation of reactive oxygen species metabolic process |
| Pathways : KEGG | Estrogen signaling pathway Prolactin signaling pathway |
| REACTOME | Q92731 [protein] |
| REACTOME Pathways | R-HSA-383280 Nuclear Receptor transcription pathway [pathway] |
| NDEx Network | ESR2 |
| Atlas of Cancer Signalling Network | ESR2 |
| Wikipedia pathways | ESR2 |
| Orthology - Evolution |
|---|
| OrthoDB | 2100 |
| GeneTree (enSembl) | ENSG00000140009 |
| Phylogenetic Trees/Animal Genes : TreeFam | ESR2 |
| Homologs : HomoloGene | ESR2 |
| Homology/Alignments : Family Browser (UCSC) | ESR2 |
| Gene fusions - Rearrangements |
|---|
| Polymorphisms : SNP, variants |
|---|
| NCBI Variation Viewer | ESR2 [hg38] |
| dbSNP Single Nucleotide Polymorphism (NCBI) | ESR2 |
| dbVar | ESR2 |
| ClinVar | ESR2 |
| 1000_Genomes | ESR2 |
| Exome Variant Server | ESR2 |
| ExAC (Exome Aggregation Consortium) | ESR2 (select the gene name) |
| Genetic variants : HAPMAP | 2100 |
| Genomic Variants (DGV) | ESR2 [DGVbeta] |
| Mutations |
|---|
| ICGC Data Portal | ESR2 |
| TCGA Data Portal | ESR2 |
| Broad Tumor Portal | ESR2 |
| OASIS Portal | ESR2 [ Somatic mutations - Copy number] |
| Somatic Mutations in Cancer : COSMIC | ESR2 |
| LOVD (Leiden Open Variation Database) | Whole genome datasets |
| LOVD (Leiden Open Variation Database) | LOVD - Leiden Open Variation Database |
| LOVD (Leiden Open Variation Database) | LOVD 3.0 shared installation |
| LOVD (Leiden Open Variation Database) | MSeqDR-LSDB Mitochondrial Disease Locus Specific Database |
| BioMuta | search ESR2 |
| DgiDB (Drug Gene Interaction Database) | ESR2 |
| DoCM (Curated mutations) | ESR2 (select the gene name) |
| CIViC (Clinical Interpretations of Variants in Cancer) | ESR2 (select a term) |
| intoGen | ESR2 |
| Impact of mutations | [PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] |
| Diseases |
|---|
| DECIPHER (Syndromes) | 14:64693751-64761128 ENSG00000140009 |
| CONAN: Copy Number Analysis | ESR2 |
| Mutations and Diseases : HGMD | ESR2 |
| OMIM | 601663 |
| Medgen | ESR2 |
| Genetic Testing Registry | ESR2
|
| NextProt | Q92731 [Medical] |
| TSGene | 2100 |
| GENETests | ESR2 |
| Huge Navigator |
ESR2 [HugePedia] |
| snp3D : Map Gene to Disease | 2100 |
| BioCentury BCIQ | ESR2 |
| ClinGen | ESR2 |
| Clinical trials, drugs, therapy |
|---|
| Chemical/Protein Interactions : CTD | 2100 |
| Chemical/Pharm GKB Gene | PA27886 |
| Clinical trial | ESR2 |
| Miscellaneous |
|---|
| canSAR (ICR) | ESR2 (select the gene name) |
| Probes |
|---|
| Litterature |
|---|
| PubMed | 499 Pubmed reference(s) in Entrez |
| GeneRIFs | Gene References Into Functions (Entrez) |
| CoreMine | ESR2 |
| EVEX | ESR2 |
| GoPubMed | ESR2 |
| iHOP | ESR2 |
