Estrogen receptor

NameEstrogen receptor
Synonyms
  • ER
  • ER-alpha
  • ESR
  • Estradiol receptor
  • NR3A1
  • Nuclear receptor subfamily 3 group A member 1
Gene NameESR1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000246|Estrogen receptor
MTMTLHTKASGMALLHQIQGNELEPLNRPQLKIPLERPLGEVYLDSSKPAVYNYPEGAAY
EFNAAAAANAQVYGQTGLPYGPGSEAAAFGSNGLGGFPPLNSVSPSPLMLLHPPPQLSPF
LQPHGQQVPYYLENEPSGYTVREAGPPAFYRPNSDNRRQGGRERLASTNDKGSMAMESAK
ETRYCAVCNDYASGYHYGVWSCEGCKAFFKRSIQGHNDYMCPATNQCTIDKNRRKSCQAC
RLRKCYEVGMMKGGIRKDRRGGRMLKHKRQRDDGEGRGEVGSAGDMRAANLWPSPLMIKR
SKKNSLALSLTADQMVSALLDAEPPILYSEYDPTRPFSEASMMGLLTNLADRELVHMINW
AKRVPGFVDLTLHDQVHLLECAWLEILMIGLVWRSMEHPGKLLFAPNLLLDRNQGKCVEG
MVEIFDMLLATSSRFRMMNLQGEEFVCLKSIILLNSGVYTFLSSTLKSLEEKDHIHRVLD
KITDTLIHLMAKAGLTLQQQHQRLAQLLLILSHIRHMSNKGMEHLYSMKCKNVVPLYDLL
LEMLDAHRLHAPTSRGGASVEETDQSHLATAGSTSSHSLQKYYITGEAEGFPATV
Number of residues595
Molecular Weight66215.45
Theoretical pI8.14
GO Classification
Functions
  • nitric-oxide synthase regulator activity
  • transcription factor activity, sequence-specific DNA binding
  • steroid hormone receptor activity
  • identical protein binding
  • beta-catenin binding
  • steroid binding
  • chromatin binding
  • transcription factor binding
  • enzyme binding
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding
  • ATPase binding
  • core promoter sequence-specific DNA binding
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
  • estrogen receptor activity
  • estrogen response element binding
  • zinc ion binding
  • RNA polymerase II transcription factor activity, estrogen-activated sequence-specific DNA binding
Processes
  • positive regulation of cytosolic calcium ion concentration
  • signal transduction
  • regulation of transcription, DNA-templated
  • positive regulation of fibroblast proliferation
  • negative regulation of sequence-specific DNA binding transcription factor activity
  • chromatin remodeling
  • uterus development
  • positive regulation of transcription, DNA-templated
  • epithelial cell development
  • response to estradiol
  • vagina development
  • positive regulation of transcription from RNA polymerase II promoter
  • epithelial cell proliferation involved in mammary gland duct elongation
  • androgen metabolic process
  • regulation of branching involved in prostate gland morphogenesis
  • phospholipase C-activating G-protein coupled receptor signaling pathway
  • intracellular steroid hormone receptor signaling pathway
  • cellular response to estradiol stimulus
  • response to estrogen
  • transcription from RNA polymerase II promoter
  • mammary gland alveolus development
  • intracellular estrogen receptor signaling pathway
  • positive regulation of nitric oxide biosynthetic process
  • positive regulation of nitric-oxide synthase activity
  • antral ovarian follicle growth
  • gene expression
  • prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis
  • positive regulation of phospholipase C activity
  • regulation of apoptotic process
  • prostate epithelial cord elongation
  • transcription, DNA-templated
  • transcription initiation from RNA polymerase II promoter
  • mammary gland branching involved in pregnancy
  • male gonad development
  • negative regulation of I-kappaB kinase/NF-kappaB signaling
  • negative regulation of gene expression
  • positive regulation of sequence-specific DNA binding transcription factor activity
Components
  • nucleus
  • plasma membrane
  • transcriptionally active chromatin
  • Golgi apparatus
  • integral component of membrane
  • cytosol
  • cytoplasm
  • nucleoplasm
  • membrane
  • nuclear chromatin
General FunctionZinc ion binding
Specific FunctionNuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID31234
UniProtKB IDP03372
UniProtKB Entry NameESR1_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0021831|Estrogen receptor (ESR1)
ATGACCATGACCCTCCACACCAAAGCATCTGGGATGGCCCTACTGCATCAGATCCAAGGG
AACGAGCTGGAGCCCCTGAACCGTCCGCAGCTCAAGATCCCCCTGGAGCGGCCCCTGGGC
GAGGTGTACCTGGACAGCAGCAAGCCCGCCGTGTACAACTACCCCGAGGGCGCCGCCTAC
GAGTTCAACGCCGCGGCCGCCGCCAACGCGCAGGTCTACGGTCAGACCGGCCTCCCCTAC
GGCCCCGGGTCTGAGGCTGCGGCGTTCGGCTCCAACGGCCTGGGGGGTTTCCCCCCACTC
AACAGCGTGTCTCCGAGCCCGCTGATGCTACTGCACCCGCCGCCGCAGCTGTCGCCTTTC
CTGCAGCCCCACGGCCAGCAGGTGCCCTACTACCTGGAGAACGAGCCCAGCGGCTACACG
GTGCGCGAGGCCGGCCCGCCGGCATTCTACAGGCCAAATTCAGATAATCGACGCCAGGGT
GGCAGAGAAAGATTGGCCAGTACCAATGACAAGGGAAGTATGGCTATGGAATCTGCCAAG
GAGACTCGCTACTGTGCAGTGTGCAATGACTATGCTTCAGGCTACCATTATGGAGTCTGG
TCCTGTGAGGGCTGCAAGGCCTTCTTCAAGAGAAGTATTCAAGGACATAACGACTATATG
TGTCCAGCCACCAACCAGTGCACCATTGATAAAAACAGGAGGAAGAGCTGCCAGGCCTGC
CGGCTCCGCAAATGCTACGAAGTGGGAATGATGAAAGGTGGGATACGAAAAGACCGAAGA
GGAGGGAGAATGTTGAAACACAAGCGCCAGAGAGATGATGGGGAGGGCAGGGGTGAAGTG
GGGTCTGCTGGAGACATGAGAGCTGCCAACCTTTGGCCAAGCCCGCTCATGATCAAACGC
TCTAAGAAGAACAGCCTGGCCTTGTCCCTGACGGCCGACCAGATGGTCAGTGCCTTGTTG
GATGCTGAGCCCCCCATACTCTATTCCGAGTATGATCCTACCAGACCCTTCAGTGAAGCT
TCGATGATGGGCTTACTGACCAACCTGGCAGACAGGGAGCTGGTTCACATGATCAACTGG
GCGAAGAGGGTGCCAGGCTTTGTGGATTTGACCCTCCATGATCAGGTCCACCTTCTAGAA
TGTGCCTGGCTAGAGATCCTGATGATTGGTCTCGTCTGGCGCTCCATGGAGCACCCAGGG
AAGCTACTGTTTGCTCCTAACTTGCTCTTGGACAGGAACCAGGGAAAATGTGTAGAGGGC
ATGGTGGAGATCTTCGACATGCTGCTGGCTACATCATCTCGGTTCCGCATGATGAATCTG
CAGGGAGAGGAGTTTGTGTGCCTCAAATCTATTATTTTGCTTAATTCTGGAGTGTACACA
TTTCTGTCCAGCACCCTGAAGTCTCTGGAAGAGAAGGACCATATCCACCGAGTCCTGGAC
AAGATCACAGACACTTTGATCCACCTGATGGCCAAGGCAGGCCTGACCCTGCAGCAGCAG
CACCAGCGGCTGGCCCAGCTCCTCCTCATCCTCTCCCACATCAGGCACATGAGTAACAAA
GGCATGGAGCATCTGTACAGCATGAAGTGCAAGAACGTGGTGCCCCTCTATGACCTGCTG
CTGGAGATGCTGGACGCCCACCGCCTACATGCGCCCACTAGCCGTGGAGGGGCATCCGTG
GAGGAGACGGACCAAAGCCACTTGGCCACTGCGGGCTCTACTTCATCGCATTCCTTGCAA
AAGTATTACATCACGGGGGAGGCAGAGGGTTTCCCTGCCACGGTCTGA
GenBank Gene IDX03635
GeneCard IDNot Available
GenAtlas IDESR1
HGNC IDHGNC:3467
Chromosome Location6
Locus6q25.1
References
  1. Green S, Walter P, Kumar V, Krust A, Bornert JM, Argos P, Chambon P: Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A. Nature. 1986 Mar 13-19;320(6058):134-9. 3754034
  2. Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J: Sequence and expression of human estrogen receptor complementary DNA. Science. 1986 Mar 7;231(4742):1150-4. 3753802
  3. Pink JJ, Wu SQ, Wolf DM, Bilimoria MM, Jordan VC: A novel 80 kDa human estrogen receptor containing a duplication of exons 6 and 7. Nucleic Acids Res. 1996 Mar 1;24(5):962-9. 8600466
  4. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. 17974005
  5. Wang Z, Zhang X, Shen P, Loggie BW, Chang Y, Deuel TF: Identification, cloning, and expression of human estrogen receptor-alpha36, a novel variant of human estrogen receptor-alpha66. Biochem Biophys Res Commun. 2005 Nov 4;336(4):1023-7. 16165085
  6. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. 14574404
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  8. Joel PB, Traish AM, Lannigan DA: Estradiol and phorbol ester cause phosphorylation of serine 118 in the human estrogen receptor. Mol Endocrinol. 1995 Aug;9(8):1041-52. 7476978
  9. Schubert EL, Lee MK, Newman B, King MC: Single nucleotide polymorphisms (SNPs) in the estrogen receptor gene and breast cancer susceptibility. J Steroid Biochem Mol Biol. 1999 Nov;71(1-2):21-7. 10619354
  10. Pfeffer U, Fecarotta E, Castagnetta L, Vidali G: Estrogen receptor variant messenger RNA lacking exon 4 in estrogen-responsive human breast cancer cell lines. Cancer Res. 1993 Feb 15;53(4):741-3. 7916651
  11. Arnold SF, Obourn JD, Jaffe H, Notides AC: Phosphorylation of the human estrogen receptor on tyrosine 537 in vivo and by src family tyrosine kinases in vitro. Mol Endocrinol. 1995 Jan;9(1):24-33. 7539106
  12. Reese JC, Katzenellenbogen BS: 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. 1992 May 15;267(14):9868-73. 1577818
  13. Arnold SF, Obourn JD, Jaffe H, Notides AC: Serine 167 is the major estradiol-induced phosphorylation site on the human estrogen receptor. Mol Endocrinol. 1994 Sep;8(9):1208-14. 7838153
  14. Stein B, Yang MX: Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta. Mol Cell Biol. 1995 Sep;15(9):4971-9. 7651415
  15. Endoh H, Maruyama K, Masuhiro Y, Kobayashi Y, Goto M, Tai H, Yanagisawa J, Metzger D, Hashimoto S, Kato S: Purification and identification of p68 RNA helicase acting as a transcriptional coactivator specific for the activation function 1 of human estrogen receptor alpha. Mol Cell Biol. 1999 Aug;19(8):5363-72. 10409727
  16. Flouriot G, Brand H, Denger S, Metivier R, Kos M, Reid G, Sonntag-Buck V, Gannon F: Identification of a new isoform of the human estrogen receptor-alpha (hER-alpha) that is encoded by distinct transcripts and that is able to repress hER-alpha activation function 1. EMBO J. 2000 Sep 1;19(17):4688-700. 10970861
  17. Metivier R, Petit FG, Valotaire Y, Pakdel F: Function of N-terminal transactivation domain of the estrogen receptor requires a potential alpha-helical structure and is negatively regulated by the A domain. Mol Endocrinol. 2000 Nov;14(11):1849-71. 11075817
  18. Bai Y, Giguere V: Isoform-selective interactions between estrogen receptors and steroid receptor coactivators promoted by estradiol and ErbB-2 signaling in living cells. Mol Endocrinol. 2003 Apr;17(4):589-99. Epub 2003 Jan 16. 12554772
  19. Li L, Haynes MP, Bender JR: Plasma membrane localization and function of the estrogen receptor alpha variant (ER46) in human endothelial cells. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4807-12. Epub 2003 Apr 7. 12682286
  20. Jiang MS, Hart GW: A subpopulation of estrogen receptors are modified by O-linked N-acetylglucosamine. J Biol Chem. 1997 Jan 24;272(4):2421-8. 8999954
  21. Porter W, Saville B, Hoivik D, Safe S: Functional synergy between the transcription factor Sp1 and the estrogen receptor. Mol Endocrinol. 1997 Oct;11(11):1569-80. 9328340
  22. Rubino D, Driggers P, Arbit D, Kemp L, Miller B, Coso O, Pagliai K, Gray K, Gutkind S, Segars J: Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action. Oncogene. 1998 May 14;16(19):2513-26. 9627117
  23. Rogatsky I, Trowbridge JM, Garabedian MJ: Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin A-CDK2 complex. J Biol Chem. 1999 Aug 6;274(32):22296-302. 10428798
  24. Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW: A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. J Biol Chem. 1999 Nov 26;274(48):34283-93. 10567404
  25. Montano MM, Ekena K, Delage-Mourroux R, Chang W, Martini P, Katzenellenbogen BS: An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens. Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6947-52. 10359819
  26. Benecke A, Chambon P, Gronemeyer H: Synergy between estrogen receptor alpha activation functions AF1 and AF2 mediated by transcription intermediary factor TIF2. EMBO Rep. 2000 Aug;1(2):151-7. 11265755
  27. Saville B, Wormke M, Wang F, Nguyen T, Enmark E, Kuiper G, Gustafsson JA, Safe S: Ligand-, cell-, and estrogen receptor subtype (alpha/beta)-dependent activation at GC-rich (Sp1) promoter elements. J Biol Chem. 2000 Feb 25;275(8):5379-87. 10681512
  28. Stoner M, Wang F, Wormke M, Nguyen T, Samudio I, Vyhlidal C, Marme D, Finkenzeller G, Safe S: Inhibition of vascular endothelial growth factor expression in HEC1A endometrial cancer cells through interactions of estrogen receptor alpha and Sp3 proteins. J Biol Chem. 2000 Jul 28;275(30):22769-79. 10816575
  29. Yahata T, Shao W, Endoh H, Hur J, Coser KR, Sun H, Ueda Y, Kato S, Isselbacher KJ, Brown M, Shioda T: Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300-binding protein. Genes Dev. 2001 Oct 1;15(19):2598-612. 11581164
  30. Teyssier C, Belguise K, Galtier F, Chalbos D: Characterization of the physical interaction between estrogen receptor alpha and JUN proteins. J Biol Chem. 2001 Sep 28;276(39):36361-9. Epub 2001 Jul 26. 11477071
  31. Chan SW, Hong W: Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription. J Biol Chem. 2001 Jul 27;276(30):28402-12. Epub 2001 May 17. 11358960
  32. Sauve F, McBroom LD, Gallant J, Moraitis AN, Labrie F, Giguere V: CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant. Mol Cell Biol. 2001 Jan;21(1):343-53. 11113208
  33. Metivier R, Penot G, Flouriot G, Pakdel F: Synergism between ERalpha transactivation function 1 (AF-1) and AF-2 mediated by steroid receptor coactivator protein-1: requirement for the AF-1 alpha-helical core and for a direct interaction between the N- and C-terminal domains. Mol Endocrinol. 2001 Nov;15(11):1953-70. 11682626
  34. Qi C, Chang J, Zhu Y, Yeldandi AV, Rao SM, Zhu YJ: Identification of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha. J Biol Chem. 2002 Aug 9;277(32):28624-30. Epub 2002 May 30. 12039952
  35. Hu YC, Shyr CR, Che W, Mu XM, Kim E, Chang C: Suppression of estrogen receptor-mediated transcription and cell growth by interaction with TR2 orphan receptor. J Biol Chem. 2002 Sep 13;277(37):33571-9. Epub 2002 Jul 1. 12093804
  36. Shao W, Halachmi S, Brown M: ERAP140, a conserved tissue-specific nuclear receptor coactivator. Mol Cell Biol. 2002 May;22(10):3358-72. 11971969
  37. Norris JD, Fan D, Sherk A, McDonnell DP: A negative coregulator for the human ER. Mol Endocrinol. 2002 Mar;16(3):459-68. 11875103
  38. Wong CW, McNally C, Nickbarg E, Komm BS, Cheskis BJ: Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14783-8. Epub 2002 Nov 1. 12415108
  39. Hsiao PW, Fryer CJ, Trotter KW, Wang W, Archer TK: BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation. Mol Cell Biol. 2003 Sep;23(17):6210-20. 12917342
  40. Bu H, Kashireddy P, Chang J, Zhu YT, Zhang Z, Zheng W, Rao SM, Zhu YJ: ERBP, a novel estrogen receptor binding protein enhancing the activity of estrogen receptor. Biochem Biophys Res Commun. 2004 Apr 23;317(1):54-9. 15047147
  41. Merot Y, Metivier R, Penot G, Manu D, Saligaut C, Gannon F, Pakdel F, Kah O, Flouriot G: The relative contribution exerted by AF-1 and AF-2 transactivation functions in estrogen receptor alpha transcriptional activity depends upon the differentiation stage of the cell. J Biol Chem. 2004 Jun 18;279(25):26184-91. Epub 2004 Apr 12. 15078875
  42. Damdimopoulos AE, Miranda-Vizuete A, Treuter E, Gustafsson JA, Spyrou G: An alternative splicing variant of the selenoprotein thioredoxin reductase is a modulator of estrogen signaling. J Biol Chem. 2004 Sep 10;279(37):38721-9. Epub 2004 Jun 14. 15199063
  43. Ikeda K, Ogawa S, Tsukui T, Horie-Inoue K, Ouchi Y, Kato S, Muramatsu M, Inoue S: Protein phosphatase 5 is a negative regulator of estrogen receptor-mediated transcription. Mol Endocrinol. 2004 May;18(5):1131-43. Epub 2004 Feb 5. 14764652
  44. Liu H, Liu K, Bodenner DL: Estrogen receptor inhibits interleukin-6 gene expression by disruption of nuclear factor kappaB transactivation. Cytokine. 2005 Aug 21;31(4):251-7. 16043358
  45. Rayala SK, den Hollander P, Balasenthil S, Yang Z, Broaddus RR, Kumar R: Functional regulation of oestrogen receptor pathway by the dynein light chain 1. EMBO Rep. 2005 Jun;6(6):538-44. 15891768
  46. Wittmann BM, Fujinaga K, Deng H, Ogba N, Montano MM: The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1. Oncogene. 2005 Aug 25;24(36):5576-88. 15940264
  47. Mo R, Rao SM, Zhu YJ: Identification of the MLL2 complex as a coactivator for estrogen receptor alpha. J Biol Chem. 2006 Jun 9;281(23):15714-20. Epub 2006 Apr 7. 16603732
  48. Rayala SK, den Hollander P, Manavathi B, Talukder AH, Song C, Peng S, Barnekow A, Kremerskothen J, Kumar R: Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells. J Biol Chem. 2006 Jul 14;281(28):19092-9. Epub 2006 May 9. 16684779
  49. Wei X, Xu H, Kufe D: MUC1 oncoprotein stabilizes and activates estrogen receptor alpha. Mol Cell. 2006 Jan 20;21(2):295-305. 16427018
  50. Lopez-Garcia J, Periyasamy M, Thomas RS, Christian M, Leao M, Jat P, Kindle KB, Heery DM, Parker MG, Buluwela L, Kamalati T, Ali S: ZNF366 is an estrogen receptor corepressor that acts through CtBP and histone deacetylases. Nucleic Acids Res. 2006;34(21):6126-36. Epub 2006 Nov 3. 17085477
  51. Gururaj AE, Singh RR, Rayala SK, Holm C, den Hollander P, Zhang H, Balasenthil S, Talukder AH, Landberg G, Kumar R: MTA1, a transcriptional activator of breast cancer amplified sequence 3. Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6670-5. Epub 2006 Apr 14. 16617102
  52. Manavathi B, Acconcia F, Rayala SK, Kumar R: An inherent role of microtubule network in the action of nuclear receptor. Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):15981-6. Epub 2006 Oct 16. 17043237
  53. Eriksson M, Samuelsson H, Samuelsson EB, Liu L, McKeehan WL, Benedikz E, Sundstrom E: The NMDAR subunit NR3A interacts with microtubule-associated protein 1S in the brain. Biochem Biophys Res Commun. 2007 Sep 14;361(1):127-32. Epub 2007 Jul 16. 17658481
  54. Zhang PJ, Zhao J, Li HY, Man JH, He K, Zhou T, Pan X, Li AL, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM: CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome. EMBO J. 2007 Apr 4;26(7):1831-42. Epub 2007 Mar 8. 17347654
  55. Han WD, Zhao YL, Meng YG, Zang L, Wu ZQ, Li Q, Si YL, Huang K, Ba JM, Morinaga H, Nomura M, Mu YM: Estrogenically regulated LRP16 interacts with estrogen receptor alpha and enhances the receptor's transcriptional activity. Endocr Relat Cancer. 2007 Sep;14(3):741-53. 17914104
  56. Luboshits G, Benayahu D: MS-KIF18A, a kinesin, is associated with estrogen receptor. J Cell Biochem. 2007 Feb 15;100(3):693-702. 17006958
  57. Meyer R, Wolf SS, Obendorf M: PRMT2, a member of the protein arginine methyltransferase family, is a coactivator of the androgen receptor. J Steroid Biochem Mol Biol. 2007 Oct;107(1-2):1-14. Epub 2007 May 24. 17587566
  58. Gururaj AE, Peng S, Vadlamudi RK, Kumar R: Estrogen induces expression of BCAS3, a novel estrogen receptor-alpha coactivator, through proline-, glutamic acid-, and leucine-rich protein-1 (PELP1). Mol Endocrinol. 2007 Aug;21(8):1847-60. Epub 2007 May 15. 17505058
  59. Yan J, Kim YS, Yang XP, Albers M, Koegl M, Jetten AM: Ubiquitin-interaction motifs of RAP80 are critical in its regulation of estrogen receptor alpha. Nucleic Acids Res. 2007;35(5):1673-86. Epub 2007 Feb 20. 17311814
  60. Zou JX, Revenko AS, Li LB, Gemo AT, Chen HW: ANCCA, an estrogen-regulated AAA+ ATPase coactivator for ERalpha, is required for coregulator occupancy and chromatin modification. Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18067-72. Epub 2007 Nov 12. 17998543
  61. Lambertini E, Tavanti E, Torreggiani E, Penolazzi L, Gambari R, Piva R: ERalpha and AP-1 interact in vivo with a specific sequence of the F promoter of the human ERalpha gene in osteoblasts. J Cell Physiol. 2008 Jul;216(1):101-10. doi: 10.1002/jcp.21379. 18247370
  62. Le Romancer M, Treilleux I, Leconte N, Robin-Lespinasse Y, Sentis S, Bouchekioua-Bouzaghou K, Goddard S, Gobert-Gosse S, Corbo L: Regulation of estrogen rapid signaling through arginine methylation by PRMT1. Mol Cell. 2008 Jul 25;31(2):212-21. doi: 10.1016/j.molcel.2008.05.025. 18657504
  63. Nettles KW, Gil G, Nowak J, Metivier R, Sharma VB, Greene GL: CBP Is a dosage-dependent regulator of nuclear factor-kappaB suppression by the estrogen receptor. Mol Endocrinol. 2008 Feb;22(2):263-72. Epub 2007 Oct 11. 17932106
  64. Molli PR, Singh RR, Lee SW, Kumar R: MTA1-mediated transcriptional repression of BRCA1 tumor suppressor gene. Oncogene. 2008 Mar 27;27(14):1971-80. Epub 2007 Oct 8. 17922032
  65. Chen M, Ni J, Zhang Y, Muyan M, Yeh S: ERAP75 functions as a coactivator to enhance estrogen receptor alpha transactivation in prostate stromal cells. Prostate. 2008 Sep 1;68(12):1273-82. doi: 10.1002/pros.20774. 18563714
  66. Li T, Li W, Lu J, Liu H, Li Y, Zhao Y: SH2D4A regulates cell proliferation via the ERalpha/PLC-gamma/PKC pathway. BMB Rep. 2009 Aug 31;42(8):516-22. 19712589
  67. Johnsen SA, Gungor C, Prenzel T, Riethdorf S, Riethdorf L, Taniguchi-Ishigaki N, Rau T, Tursun B, Furlow JD, Sauter G, Scheffner M, Pantel K, Gannon F, Bach I: Regulation of estrogen-dependent transcription by the LIM cofactors CLIM and RLIM in breast cancer. Cancer Res. 2009 Jan 1;69(1):128-36. doi: 10.1158/0008-5472.CAN-08-1630. 19117995
  68. Massinen S, Tammimies K, Tapia-Paez I, Matsson H, Hokkanen ME, Soderberg O, Landegren U, Castren E, Gustafsson JA, Treuter E, Kere J: Functional interaction of DYX1C1 with estrogen receptors suggests involvement of hormonal pathways in dyslexia. Hum Mol Genet. 2009 Aug 1;18(15):2802-12. doi: 10.1093/hmg/ddp215. Epub 2009 May 7. 19423554
  69. Gionet N, Jansson D, Mader S, Pratt MA: NF-kappaB and estrogen receptor alpha interactions: Differential function in estrogen receptor-negative and -positive hormone-independent breast cancer cells. J Cell Biochem. 2009 Jun 1;107(3):448-59. doi: 10.1002/jcb.22141. 19350539
  70. Stanisic V, Malovannaya A, Qin J, Lonard DM, O'Malley BW: OTU Domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) deubiquitinates estrogen receptor (ER) alpha and affects ERalpha transcriptional activity. J Biol Chem. 2009 Jun 12;284(24):16135-45. doi: 10.1074/jbc.M109.007484. Epub 2009 Apr 21. 19383985
  71. Giamas G, Castellano L, Feng Q, Knippschild U, Jacob J, Thomas RS, Coombes RC, Smith CL, Jiao LR, Stebbing J: CK1delta modulates the transcriptional activity of ERalpha via AIB1 in an estrogen-dependent manner and regulates ERalpha-AIB1 interactions. Nucleic Acids Res. 2009 May;37(9):3110-23. doi: 10.1093/nar/gkp136. Epub 2009 Apr 1. 19339517
  72. Wortham NC, Ahamed E, Nicol SM, Thomas RS, Periyasamy M, Jiang J, Ochocka AM, Shousha S, Huson L, Bray SE, Coombes RC, Ali S, Fuller-Pace FV: The DEAD-box protein p72 regulates ERalpha-/oestrogen-dependent transcription and cell growth, and is associated with improved survival in ERalpha-positive breast cancer. Oncogene. 2009 Nov 19;28(46):4053-64. doi: 10.1038/onc.2009.261. Epub 2009 Aug 31. 19718048
  73. Zusev M, Benayahu D: The regulation of MS-KIF18A expression and cross talk with estrogen receptor. PLoS One. 2009 Jul 28;4(7):e6407. doi: 10.1371/journal.pone.0006407. 19636373
  74. Koyama S, Wada-Hiraike O, Nakagawa S, Tanikawa M, Hiraike H, Miyamoto Y, Sone K, Oda K, Fukuhara H, Nakagawa K, Kato S, Yano T, Taketani Y: Repression of estrogen receptor beta function by putative tumor suppressor DBC1. Biochem Biophys Res Commun. 2010 Feb 12;392(3):357-62. doi: 10.1016/j.bbrc.2010.01.025. Epub 2010 Jan 13. 20074560
  75. Pradhan M, Bembinster LA, Baumgarten SC, Frasor J: Proinflammatory cytokines enhance estrogen-dependent expression of the multidrug transporter gene ABCG2 through estrogen receptor and NF{kappa}B cooperativity at adjacent response elements. J Biol Chem. 2010 Oct 8;285(41):31100-6. doi: 10.1074/jbc.M110.155309. Epub 2010 Aug 12. 20705611
  76. Dong XY, Sun X, Guo P, Li Q, Sasahara M, Ishii Y, Dong JT: ATBF1 inhibits estrogen receptor (ER) function by selectively competing with AIB1 for binding to the ER in ER-positive breast cancer cells. J Biol Chem. 2010 Oct 22;285(43):32801-9. doi: 10.1074/jbc.M110.128330. Epub 2010 Aug 18. 20720010
  77. Park Y, Park J, Lee Y, Lim W, Oh BC, Shin C, Kim W, Lee Y: Mammalian MST2 kinase and human Salvador activate and reduce estrogen receptor alpha in the absence of ligand. J Mol Med (Berl). 2011 Feb;89(2):181-91. doi: 10.1007/s00109-010-0698-y. Epub 2010 Nov 23. 21104395
  78. Kim KH, Toomre D, Bender JR: Splice isoform estrogen receptors as integral transmembrane proteins. Mol Biol Cell. 2011 Nov;22(22):4415-23. doi: 10.1091/mbc.E11-05-0416. Epub 2011 Sep 21. 21937726
  79. Heldring N, Isaacs GD, Diehl AG, Sun M, Cheung E, Ranish JA, Kraus WL: Multiple sequence-specific DNA-binding proteins mediate estrogen receptor signaling through a tethering pathway. Mol Endocrinol. 2011 Apr;25(4):564-74. doi: 10.1210/me.2010-0425. Epub 2011 Feb 17. 21330404
  80. Giamas G, Filipovic A, Jacob J, Messier W, Zhang H, Yang D, Zhang W, Shifa BA, Photiou A, Tralau-Stewart C, Castellano L, Green AR, Coombes RC, Ellis IO, Ali S, Lenz HJ, Stebbing J: Kinome screening for regulators of the estrogen receptor identifies LMTK3 as a new therapeutic target in breast cancer. Nat Med. 2011 Jun;17(6):715-9. doi: 10.1038/nm.2351. Epub 2011 May 22. 21602804
  81. Pedram A, Razandi M, Deschenes RJ, Levin ER: DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors. Mol Biol Cell. 2012 Jan;23(1):188-99. doi: 10.1091/mbc.E11-07-0638. Epub 2011 Oct 26. 22031296
  82. Pradhan M, Baumgarten SC, Bembinster LA, Frasor J: CBP mediates NF-kappaB-dependent histone acetylation and estrogen receptor recruitment to an estrogen response element in the BIRC3 promoter. Mol Cell Biol. 2012 Jan;32(2):569-75. doi: 10.1128/MCB.05869-11. Epub 2011 Nov 14. 22083956
  83. Li S, Wang M, Ao X, Chang AK, Yang C, Zhao F, Bi H, Liu Y, Xiao L, Wu H: CLOCK is a substrate of SUMO and sumoylation of CLOCK upregulates the transcriptional activity of estrogen receptor-alpha. Oncogene. 2013 Oct 10;32(41):4883-91. doi: 10.1038/onc.2012.518. Epub 2012 Nov 19. 23160374
  84. Feng Y, Singleton D, Guo C, Gardner A, Pakala S, Kumar R, Jensen E, Zhang J, Khan S: DNA homologous recombination factor SFR1 physically and functionally interacts with estrogen receptor alpha. PLoS One. 2013 Jul 9;8(7):e68075. doi: 10.1371/journal.pone.0068075. Print 2013. 23874500
  85. Yoo HM, Kang SH, Kim JY, Lee JE, Seong MW, Lee SW, Ka SH, Sou YS, Komatsu M, Tanaka K, Lee ST, Noh DY, Baek SH, Jeon YJ, Chung CH: Modification of ASC1 by UFM1 is crucial for ERalpha transactivation and breast cancer development. Mol Cell. 2014 Oct 23;56(2):261-74. doi: 10.1016/j.molcel.2014.08.007. Epub 2014 Sep 11. 25219498
  86. Schwabe JW, Neuhaus D, Rhodes D: Solution structure of the DNA-binding domain of the oestrogen receptor. Nature. 1990 Nov 29;348(6300):458-61. 2247153
  87. Schwabe JW, Chapman L, Finch JT, Rhodes D: The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: how receptors discriminate between their response elements. Cell. 1993 Nov 5;75(3):567-78. 8221895
  88. Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, Ohman L, Greene GL, Gustafsson JA, Carlquist M: Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 1997 Oct 16;389(6652):753-8. 9338790
  89. Tanenbaum DM, Wang Y, Williams SP, Sigler PB: Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains. Proc Natl Acad Sci U S A. 1998 May 26;95(11):5998-6003. 9600906
  90. Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL: The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell. 1998 Dec 23;95(7):927-37. 9875847
  91. Maalouf GJ, Xu W, Smith TF, Mohr SC: Homology model for the ligand-binding domain of the human estrogen receptor. J Biomol Struct Dyn. 1998 Apr;15(5):841-51. 9619507
  92. Tora L, Mullick A, Metzger D, Ponglikitmongkol M, Park I, Chambon P: The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties. EMBO J. 1989 Jul;8(7):1981-6. 2792078
  93. McInerney EM, Ince BA, Shapiro DJ, Katzenellenbogen BS: A transcriptionally active estrogen receptor mutant is a novel type of dominant negative inhibitor of estrogen action. Mol Endocrinol. 1996 Dec;10(12):1519-26. 8961262
  94. Anderson TI, Wooster R, Laake K, Collins N, Warren W, Skrede M, Elles R, Tveit KM, Johnston SR, Dowsett M, Olsen AO, Moller P, Stratton MR, Borresen-Dale AL: Screening for ESR mutations in breast and ovarian cancer patients. Hum Mutat. 1997;9(6):531-6. 9195227
  95. Becherini L, Gennari L, Masi L, Mansani R, Massart F, Morelli A, Falchetti A, Gonnelli S, Fiorelli G, Tanini A, Brandi ML: Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor alpha gene and their relationship to bone mass variation in postmenopausal Italian women. Hum Mol Genet. 2000 Aug 12;9(13):2043-50. 10942433
  96. Vivacqua A, Lappano R, De Marco P, Sisci D, Aquila S, De Amicis F, Fuqua SA, Ando S, Maggiolini M: G protein-coupled receptor 30 expression is up-regulated by EGF and TGF alpha in estrogen receptor alpha-positive cancer cells. Mol Endocrinol. 2009 Nov;23(11):1815-26. doi: 10.1210/me.2009-0120. Epub 2009 Sep 11. 19749156
  97. Chanock SJ, Burdett L, Yeager M, Llaca V, Langerod A, Presswalla S, Kaaresen R, Strausberg RL, Gerhard DS, Kristensen V, Perou CM, Borresen-Dale AL: Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas. Breast Cancer Res. 2007;9(1):R5. 17224074
  98. Quaynor SD, Stradtman EW Jr, Kim HG, Shen Y, Chorich LP, Schreihofer DA, Layman LC: Delayed puberty and estrogen resistance in a woman with estrogen receptor alpha variant. N Engl J Med. 2013 Jul 11;369(2):164-71. doi: 10.1056/NEJMoa1303611. 23841731