Estrogen receptor beta

Available structures
PDBOrtholog search: PDBe RCSB
Aliases ESR2, ER-BETA, ESR-BETA, ESRB, ESTRB, Erb, NR3A2, estrogen receptor 2
External IDs OMIM: 601663 MGI: 109392 HomoloGene: 1100 GeneCards: ESR2
Targeted by Drug
17β-estradiol, diethylstilbestrol, estriol, estrone, ethinyl estradiol, genistein, tamoxifen, bisphenol a, lasofoxifene, bazedoxifene, raloxifene[1]
RNA expression pattern

More reference expression data
Species Human Mouse









RefSeq (mRNA)


RefSeq (protein)


Location (UCSC) Chr 14: 64.08 – 64.34 Mb Chr 12: 76.12 – 76.18 Mb
PubMed search [2] [3]
View/Edit HumanView/Edit Mouse

Estrogen receptor beta (ER-β), also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2), is one of two main types of estrogen receptor, a nuclear receptor which is activated by the sex hormone estrogen.[4] In humans, ER-β is encoded by the ESR2 gene.[5]


ER-β is a member of the family of estrogen receptors and the superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17-β-estradiol, estriol or related ligands, the encoded protein forms homo-dimers or hetero-dimers with estrogen receptor α that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized.[6]

ER-β may have anti-proliferative effects and therefore oppose the actions of ERα in reproductive tissue.[7] ER-β may also have an important role in adaptive function of the lung during pregnancy.[8]

ER-β is a potent tumor suppressor and plays a crucial role in many cancer types such as prostate cancer.[9][10]

Tissue distribution

ER-β is expressed by many tissues including the uterus,[11] blood monocytes and tissue macrophages, colonic and pulmonary epithelial cells and in prostatic epithelium and in malignant counterparts of these tissues. Also, ER-β is found throughout the brain at different concentrations in different neuron clusters.[12][13]

ER-β abnormalities

ER-β function is related to various cardiovascular targets including ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein A1 (ApoA-1). Polymorphism may affect ER-β function and lead to altered responses in postmenopausal women receiving hormone replacement therapy.[14]



Agonists of ER-β selective over ERα include:


Antagonists of ER-β selective over ERα include:


Estrogen receptor beta has been shown to interact with:


  1. "Drugs that physically interact with Estrogen receptor beta view/edit references on wikidata".
  2. "Human PubMed Reference:".
  3. "Mouse PubMed Reference:".
  4. Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA (June 1996). "Cloning of a novel receptor expressed in rat prostate and ovary". Proc. Natl. Acad. Sci. U.S.A. 93 (12): 5925–30. doi:10.1073/pnas.93.12.5925. PMC 39164Freely accessible. PMID 8650195.
  5. Mosselman S, Polman J, Dijkema R (August 1996). "ER beta: identification and characterization of a novel human estrogen receptor". FEBS Lett. 392 (1): 49–53. doi:10.1016/0014-5793(96)00782-X. PMID 8769313.
  6. "Entrez Gene: ESR2 estrogen receptor 2 (ER beta)".
  7. Weihua Z, Saji S, Mäkinen S, Cheng G, Jensen EV, Warner M, Gustafsson JA (2000). "Estrogen receptor (ER) β, a modulator of ERα in the uterus". Proc. Natl. Acad. Sci. U.S.A. 97 (11): 5936–41. doi:10.1073/pnas.97.11.5936. PMC 18537Freely accessible. PMID 10823946.
  8. Carey MA, Card JW, Voltz JW, Germolec DR, Korach KS, Zeldin DC (2007). "The impact of sex and sex hormones on lung physiology and disease: lessons from animal studies". Am. J. Physiol. Lung Cell Mol. Physiol. 293 (2): L272–8. doi:10.1152/ajplung.00174.2007. PMID 17575008.
  9. Stettner M, Kaulfuss S, Burfeind P, Schweyer S, Strauss A, Ringert RH, Thelen P (2007). "The relevance of estrogen receptor-beta expression to the antiproliferative effects observed with histone deacetylase inhibitors and phytoestrogens in prostate cancer treatment". Mol Cancer Ther. 5 (10): 2626–33. doi:10.1158/1535-7163.MCT-07-0197. PMID 17913855.
  10. Kyriakidis I, Papaioannidou P (June 2016). "Estrogen receptor beta and ovarian cancer: a key to pathogenesis and response to therapy". Arch Gynecol Obstet. 293 (6): 1161–8. doi:10.1007/s00404-016-4027-8. PMID 26861465.
  11. Hapangama DK, Kamal AM, Bulmer JN (Mar 2015). "Estrogen receptor β: the guardian of the endometrium". Human Reproduction Update. 21 (2): 174–193. doi:10.1093/humupd/dmu053. PMID 25305176.
  12. Couse JF, Lindzey J, Grandien K, Gustafsson JA, Korach KS (1997). "Tissue distribution and quantitative analysis of estrogen receptor-alpha (ERα) and estrogen receptor-beta (ER-β) messenger ribonucleic acid in the wild-type and ERα-knockout mouse". Endocrinology. 138 (11): 4613–21. doi:10.1210/en.138.11.4613. PMID 9348186.
  13. Koehler KF, Helguero LA, Haldosén LA, Warner M, Gustafsson JA (2005). "Reflections on the discovery and significance of estrogen receptor β". Endocr. Rev. 26 (3): 465–78. doi:10.1210/er.2004-0027. PMID 15857973.
  14. Darabi M, Ani M, Panjehpour M, Rabbani M, Movahedian A, Zarean E (January–February 2011). "Effect of estrogen receptor beta A1730G polymorphism on ABCA1 gene expression response to postmenopausal hormone replacement therapy". Genetic testing and molecular biomarkers. 15 (1-2): 11–15. doi:10.1089/gtmb.2010.0106. PMID 21117950.
  15. 1 2 3 4 5 6 7 Hajirahimkhan A, Dietz BM, Bolton JL (May 2013). "Botanical modulation of menopausal symptoms: mechanisms of action?". Planta Medica. 79 (7): 538–53. doi:10.1055/s-0032-1328187. PMC 3800090Freely accessible. PMID 23408273.
  16. Minutolo F, Bertini S, Granchi C, Marchitiello T, Prota G, Rapposelli S, Tuccinardi T, Martinelli A, Gunther JR, Carlson KE, Katzenellenbogen JA, Macchia M (2009). "Structural evolutions of salicylaldoximes as selective agonists for estrogen receptor beta". J. Med. Chem. 52 (3): 858–67. doi:10.1021/jm801458t. PMID 19128016.
  17. Nakamura Y, Felizola SJ, Kurotaki Y, Fujishima F, McNamara KM, Suzuki T, Arai Y, Sasano H (May 2013). "Cyclin D1 (CCND1) expression is involved in estrogen receptor beta (ER-β) in human prostate cancer". Prostate. 173 (6): 590–5. doi:10.1002/pros.22599. PMID 23060014.
  18. Ogawa S, Inoue S, Watanabe T, Hiroi H, Orimo A, Hosoi T, Ouchi Y, Muramatsu M (February 1998). "The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER alpha in vivo and in vitro". Biochem. Biophys. Res. Commun. 243 (1): 122–6. doi:10.1006/bbrc.1997.7893. PMID 9473491.
  19. 1 2 Poelzl G, Kasai Y, Mochizuki N, Shaul PW, Brown M, Mendelsohn ME (March 2000). "Specific association of estrogen receptor β with the cell cycle spindle assembly checkpoint protein, MAD2". Proc. Natl. Acad. Sci. U.S.A. 97 (6): 2836–9. doi:10.1073/pnas.050580997. PMC 16016Freely accessible. PMID 10706629.
  20. Wong CW, Komm B, Cheskis BJ (June 2001). "Structure-function evaluation of ER alpha and beta interplay with SRC family coactivators. ER selective ligands". Biochemistry. 40 (23): 6756–65. doi:10.1021/bi010379h. PMID 11389589.
  21. Leo C, Li H, Chen JD (February 2000). "Differential mechanisms of nuclear receptor regulation by receptor-associated coactivator 3". J. Biol. Chem. 275 (8): 5976–82. doi:10.1074/jbc.275.8.5976. PMID 10681591.
  22. Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW (February 2001). "Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2". Mol. Endocrinol. 15 (2): 241–54. doi:10.1210/me.15.2.241. PMID 11158331.
  23. Ko L, Cardona GR, Iwasaki T, Bramlett KS, Burris TP, Chin WW (January 2002). "Ser-884 adjacent to the LXXLL motif of coactivator TRBP defines selectivity for ERs and TRs". Mol. Endocrinol. 16 (1): 128–40. doi:10.1210/mend.16.1.0755. PMID 11773444.
  24. Jung DJ, Na SY, Na DS, Lee JW (January 2002). "Molecular cloning and characterization of CAPER, a novel coactivator of activating protein-1 and estrogen receptors". J. Biol. Chem. 277 (2): 1229–34. doi:10.1074/jbc.M110417200. PMID 11704680.
  25. Migliaccio A, Castoria G, Di Domenico M, de Falco A, Bilancio A, Lombardi M, Barone MV, Ametrano D, Zannini MS, Abbondanza C, Auricchio F (October 2000). "Steroid-induced androgen receptor–oestradiol receptor β–Src complex triggers prostate cancer cell proliferation". EMBO J. 19 (20): 5406–17. doi:10.1093/emboj/19.20.5406. PMC 314017Freely accessible. PMID 11032808.
  26. Slentz-Kesler K, Moore JT, Lombard M, Zhang J, Hollingsworth R, Weiner MP (October 2000). "Identification of the human Mnk2 gene (MKNK2) through protein interaction with estrogen receptor beta". Genomics. 69 (1): 63–71. doi:10.1006/geno.2000.6299. PMID 11013076.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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