Estrogen receptor alpha

ESR1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases ESR1, ER, ESR, ESRA, ESTRR, Era, NR3A1, estrogen receptor 1
External IDs OMIM: 133430 MGI: 1352467 HomoloGene: 47906 GeneCards: ESR1
Genetically Related Diseases
obesity, breast cancer, Alcohol dependence[1]
Targeted by Drug
17β-estradiol, diethylstilbestrol, estriol, estrone, ethinyl estradiol, raloxifene, tamoxifen, lasofoxifene, bazedoxifene, hexestrol[2]
Orthologs
Species Human Mouse
Entrez

2099

13982

Ensembl

ENSG00000091831

ENSMUSG00000019768

UniProt

P03372

P19785

RefSeq (mRNA)

NM_007956
NM_001302531
NM_001302532
NM_001302533

RefSeq (protein)

NP_001289460.1
NP_001289461.1
NP_031982.1

Location (UCSC) Chr 6: 151.66 – 152.13 Mb Chr 10: 4.61 – 5.01 Mb
PubMed search [3] [4]
Wikidata
View/Edit HumanView/Edit Mouse

Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ESR1 (EStrogen Receptor 1).[5][6][7]

Structure

The estrogen receptor (ER) is a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription.[8] Alternative splicing results in several ESR1 mRNA transcripts, which differ primarily in their 5-prime untranslated regions. The translated receptors show less variability.[9][10]

Ligands

Agonists

Agonists of ERα selective over ERβ include:

Antagonists

Antagonists of ERα selective over ERβ include:

Clinical significance

Estrogen insensitivity syndrome is a very rare condition characterized by a defective ERα that is insensitive to estrogens.[11][12][13][14] The clinical presentation of a female was observed to include absence of breast development and other female secondary sexual characteristics at puberty, hypoplastic uterus, primary amenorrhea, enlarged multicystic ovaries and associated lower abdominal pain, mild hyperandrogenism (manifested as cystic acne), and delayed bone maturation as well as an increased rate of bone turnover.[14] The clinical presentation in a male was reported to include lack of epiphyseal closure, tall stature, osteoporosis, and poor sperm viability.[13] Both individuals were completely insensitive to exogenous estrogen treatment, even with high doses.[13][14]

Coactivators

Coactivators of ER-α include:

Interactions

Estrogen receptor alpha has been shown to interact with:

References

  1. "Diseases that are genetically associated with ESR1 view/edit references on wikidata".
  2. "Drugs that physically interact with Estrogen receptor view/edit references on wikidata".
  3. "Human PubMed Reference:".
  4. "Mouse PubMed Reference:".
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Further reading

  • McDonnell DP, Norris JD (2002). "Connections and regulation of the human estrogen receptor". Science. 296 (5573): 1642–4. doi:10.1126/science.1071884. PMID 12040178. 
  • Simoncini T, Fornari L, Mannella P, Varone G, Caruso A, Liao JK, Genazzani AR (2003). "Novel non-transcriptional mechanisms for estrogen receptor signaling in the cardiovascular system. Interaction of estrogen receptor alpha with phosphatidylinositol 3-OH kinase". Steroids. 67 (12): 935–9. doi:10.1016/S0039-128X(02)00040-5. PMID 12398989. 
  • Lannigan DA (2003). "Estrogen receptor phosphorylation". Steroids. 68 (1): 1–9. doi:10.1016/S0039-128X(02)00110-1. PMID 12475718. 
  • Herrington DM (2003). "Role of estrogen receptor-alpha in pharmacogenetics of estrogen action". Curr. Opin. Lipidol. 14 (2): 145–50. doi:10.1097/00041433-200304000-00005. PMID 12642782. 
  • Tanaka Y, Sasaki M, Kaneuchi M, Fujimoto S, Dahiya R (2004). "Estrogen receptor alpha polymorphisms and renal cell carcinoma--a possible risk". Mol. Cell. Endocrinol. 202 (1–2): 109–16. doi:10.1016/S0303-7207(03)00071-6. PMID 12770739. 
  • Ali S, Coombes RC (2004). "Estrogen receptor alpha in human breast cancer: occurrence and significance". Journal of Mammary Gland Biology and Neoplasia. 5 (3): 271–81. doi:10.1023/A:1009594727358. PMID 14973389. 
  • Olsson H (2004). "Estrogen receptor content in malignant breast tumors in men--a review". Journal of Mammary Gland Biology and Neoplasia. 5 (3): 283–7. doi:10.1023/A:1009546811429. PMID 14973390. 
  • Surmacz E, Bartucci M (2005). "Role of estrogen receptor alpha in modulating IGF-I receptor signaling and function in breast cancer". J. Exp. Clin. Cancer Res. 23 (3): 385–94. PMID 15595626. 
  • Evinger AJ, Levin ER (2005). "Requirements for estrogen receptor alpha membrane localization and function". Steroids. 70 (5–7): 361–3. doi:10.1016/j.steroids.2005.02.015. PMID 15862818. 
  • Wang CL, Tang XY, Chen WQ, Su YX, Zhang CX, Chen YM (2007). "Association of estrogen receptor alpha gene polymorphisms with bone mineral density in Chinese women: a meta-analysis". Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 18 (3): 295–305. doi:10.1007/s00198-006-0239-2. PMID 17089081. 
  • Keaveney M, Klug J, Gannon F (1992). "Sequence analysis of the 5' flanking region of the human estrogen receptor gene". DNA Seq. 2 (6): 347–58. doi:10.3109/10425179209020816. PMID 1476547. 
  • Piva R, Gambari R, Zorzato F, Kumar L, del Senno L (1992). "Analysis of upstream sequences of the human estrogen receptor gene". Biochem. Biophys. Res. Commun. 183 (3): 996–1002. doi:10.1016/S0006-291X(05)80289-X. PMID 1567414. 
  • Reese JC, Katzenellenbogen BS (1992). "Characterization of a temperature-sensitive mutation in the hormone binding domain of the human estrogen receptor. Studies in cell extracts and intact cells and their implications for hormone-dependent transcriptional activation". J. Biol. Chem. 267 (14): 9868–73. PMID 1577818. 
  • Dotzlaw H, Alkhalaf M, Murphy LC (1992). "Characterization of estrogen receptor variant mRNAs from human breast cancers". Mol. Endocrinol. 6 (5): 773–85. doi:10.1210/me.6.5.773. PMID 1603086. 
  • Keaveney M, Klug J, Dawson MT, Nestor PV, Neilan JG, Forde RC, Gannon F (1991). "Evidence for a previously unidentified upstream exon in the human oestrogen receptor gene". J. Mol. Endocrinol. 6 (1): 111–5. doi:10.1677/jme.0.0060111. PMID 2015052. 
  • Reese JC, Katzenellenbogen BS (1991). "Mutagenesis of cysteines in the hormone binding domain of the human estrogen receptor. Alterations in binding and transcriptional activation by covalently and reversibly attaching ligands". J. Biol. Chem. 266 (17): 10880–7. PMID 2040605. 
  • Schwabe JW, Neuhaus D, Rhodes D (1991). "Solution structure of the DNA-binding domain of the oestrogen receptor". Nature. 348 (6300): 458–61. doi:10.1038/348458a0. PMID 2247153. 
  • Tora L, Mullick A, Metzger D, Ponglikitmongkol M, Park I, Chambon P (1989). "The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties". EMBO J. 8 (7): 1981–6. PMC 401066Freely accessible. PMID 2792078. 
  • Ponglikitmongkol M, Green S, Chambon P (1989). "Genomic organization of the human oestrogen receptor gene". EMBO J. 7 (11): 3385–8. PMC 454836Freely accessible. PMID 3145193. 
  • Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J (1986). "Sequence and expression of human estrogen receptor complementary DNA". Science. 231 (4742): 1150–4. doi:10.1126/science.3753802. PMID 3753802. 

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