Estrogen Receptor Alpha (ERa)

ER-A1; ER; ESR; ESR1; ESRA; NR3A1; NR3-A1; Estrogen Receptor 1; Nuclear Receptor Subfamily 3,Group A,Member 1

SPN	V762
HGNC	3467
MGI	1352467
PubMed	14973389
RGD	2581
UniProt	P03372
Wiki	ERA

Estrogen receptor structure-function is a vast topic and the subject of very active current research. Nuclear receptors are a large family of structurally related ligand-inducible transcription factors, including steroid receptors (SRs), thyroid/retinoids receptors (TR, RARs and RXRs), vitamin D receptors (VDR), LXR, PPARs, estrogen receptors (ERα and ERβ), and orphan receptors for which no ligand has been yet identified. While having in common a modular structure, they are activated by distinct lipophilic small molecules such as glucocorticoids, progesterone, estrogens, retinoids, and fatty acid derivatives.All nuclear receptors have a hydrophobic pocket into which its specific ligand binds, with helix 12 (H12) being the key response element of NRs.

Reference

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Nature 320:134-139(1986) [PubMed] [Europe PMC] [Abstract]

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Science 231:1150-1154(1986) [PubMed] [Europe PMC] [Abstract]

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BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]

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"Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta."
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"Purification and identification of p68 RNA helicase acting as a transcriptional coactivator specific for the activation function 1 of human estrogen receptor alpha."
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"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. 19:4688-4700(2000) [PubMed] [Europe PMC] [Abstract]

"Function of N-terminal transactivation domain of the estrogen receptor requires a potential alpha-helical structure and is negatively regulated by the A domain."
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Mol. Endocrinol. 17:589-599(2003) [PubMed] [Europe PMC] [Abstract]

"Plasma membrane localization and function of the estrogen receptor alpha variant (ER46) in human endothelial cells."
Proc. Natl. Acad. Sci. U.S.A. 100:4807-4812(2003) [PubMed] [Europe PMC] [Abstract]

"A subpopulation of estrogen receptors are modified by O-linked N-acetylglucosamine."
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Mol. Endocrinol. 11:1569-1580(1997) [PubMed] [Europe PMC] [Abstract]

"Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action."
Oncogene 16:2513-2526(1998) [PubMed] [Europe PMC] [Abstract]

"Potentiation of human estrogen receptor alpha transcriptional activation through phosphorylation of serines 104 and 106 by the cyclin A-CDK2 complex."
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"A nuclear factor ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo."
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"An estrogen receptor-selective coregulator that potentiates the effectiveness of antiestrogens and represses the activity of estrogens."
Proc. Natl. Acad. Sci. U.S.A. 96:6947-6952(1999) [PubMed] [Europe PMC] [Abstract]

"Synergy between estrogen receptor alpha activation functions AF1 and AF2 mediated by transcription intermediary factor TIF2."
EMBO Rep. 1:151-157(2000) [PubMed] [Europe PMC] [Abstract]

"Ligand-, cell-, and estrogen receptor subtype (alpha/beta)-dependent activation at GC-rich (Sp1) promoter elements."
J. Biol. Chem. 275:5379-5387(2000) [PubMed] [Europe PMC] [Abstract]

"Inhibition of vascular endothelial growth factor expression in HEC1A endometrial cancer cells through interactions of estrogen receptor alpha and Sp3 proteins."
J. Biol. Chem. 275:22769-22779(2000) [PubMed] [Europe PMC] [Abstract]

"Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300-binding protein."
Genes Dev. 15:2598-2612(2001) [PubMed] [Europe PMC] [Abstract]

"Characterization of the physical interaction between estrogen receptor alpha and JUN proteins."
J. Biol. Chem. 276:36361-36369(2001) [PubMed] [Europe PMC] [Abstract]

"Retinoblastoma-binding protein 2 (Rbp2) potentiates nuclear hormone receptor-mediated transcription."
J. Biol. Chem. 276:28402-28412(2001) [PubMed] [Europe PMC] [Abstract]

"CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant."
Mol. Cell. Biol. 21:343-353(2001) [PubMed] [Europe PMC] [Abstract]

"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. 15:1953-1970(2001) [PubMed] [Europe PMC] [Abstract]

"Identification of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha."
J. Biol. Chem. 277:28624-28630(2002) [PubMed] [Europe PMC] [Abstract]

"Suppression of estrogen receptor-mediated transcription and cell growth by interaction with TR2 orphan receptor."
J. Biol. Chem. 277:33571-33579(2002) [PubMed] [Europe PMC] [Abstract]

"ERAP140, a conserved tissue-specific nuclear receptor coactivator."
Mol. Cell. Biol. 22:3358-3372(2002) [PubMed] [Europe PMC] [Abstract]

"A negative coregulator for the human ER."
Mol. Endocrinol. 16:459-468(2002) [PubMed] [Europe PMC] [Abstract]

"Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade."
Proc. Natl. Acad. Sci. U.S.A. 99:14783-14788(2002) [PubMed] [Europe PMC] [Abstract]

"BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation."
Mol. Cell. Biol. 23:6210-6220(2003) [PubMed] [Europe PMC] [Abstract]

"ERBP, a novel estrogen receptor binding protein enhancing the activity of estrogen receptor."
Biochem. Biophys. Res. Commun. 317:54-59(2004) [PubMed] [Europe PMC] [Abstract]

"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. 279:26184-26191(2004) [PubMed] [Europe PMC] [Abstract]

"An alternative splicing variant of the selenoprotein thioredoxin reductase is a modulator of estrogen signaling."
J. Biol. Chem. 279:38721-38729(2004) [PubMed] [Europe PMC] [Abstract]

"Protein phosphatase 5 is a negative regulator of estrogen receptor-mediated transcription."
Mol. Endocrinol. 18:1131-1143(2004) [PubMed] [Europe PMC] [Abstract]

"Estrogen receptor inhibits interleukin-6 gene expression by disruption of nuclear factor kappaB transactivation."
Cytokine 31:251-257(2005) [PubMed] [Europe PMC] [Abstract]

"Functional regulation of oestrogen receptor pathway by the dynein light chain 1."
EMBO Rep. 6:538-544(2005) [PubMed] [Europe PMC] [Abstract]

Erratum
EMBO Rep. 6:1101-1101(2005)

"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 24:5576-5588(2005) [PubMed] [Europe PMC] [Abstract]

"Identification of the MLL2 complex as a coactivator for estrogen receptor alpha."
J. Biol. Chem. 281:15714-15720(2006) [PubMed] [Europe PMC] [Abstract]

"Essential role of KIBRA in co-activator function of dynein light chain 1 in mammalian cells."
J. Biol. Chem. 281:19092-19099(2006) [PubMed] [Europe PMC] [Abstract]

"MUC1 oncoprotein stabilizes and activates estrogen receptor alpha."
Mol. Cell 21:295-305(2006) [PubMed] [Europe PMC] [Abstract]

"ZNF366 is an estrogen receptor corepressor that acts through CtBP and histone deacetylases."
Nucleic Acids Res. 34:6126-6136(2006) [PubMed] [Europe PMC] [Abstract]

"MTA1, a transcriptional activator of breast cancer amplified sequence 3."
Proc. Natl. Acad. Sci. U.S.A. 103:6670-6675(2006) [PubMed] [Europe PMC] [Abstract]

Erratum
Proc. Natl. Acad. Sci. U.S.A. 110:4147-4148(2013)

"An inherent role of microtubule network in the action of nuclear receptor."
Proc. Natl. Acad. Sci. U.S.A. 103:15981-15986(2006) [PubMed] [Europe PMC] [Abstract]

"The NMDAR subunit NR3A interacts with microtubule-associated protein 1S in the brain."
Biochem. Biophys. Res. Commun. 361:127-132(2007) [PubMed] [Europe PMC] [Abstract]

"CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome."
EMBO J. 26:1831-1842(2007) [PubMed] [Europe PMC] [Abstract]

"Estrogenically regulated LRP16 interacts with estrogen receptor alpha and enhances the receptor's transcriptional activity."
Endocr. Relat. Cancer 14:741-753(2007) [PubMed] [Europe PMC] [Abstract]

"MS-KIF18A, a kinesin, is associated with estrogen receptor."
J. Cell. Biochem. 100:693-702(2007) [PubMed] [Europe PMC] [Abstract]

"PRMT2, a member of the protein arginine methyltransferase family, is a coactivator of the androgen receptor."
J. Steroid Biochem. Mol. Biol. 107:1-14(2007) [PubMed] [Europe PMC] [Abstract]

"Estrogen induces expression of BCAS3, a novel estrogen receptor-alpha coactivator, through proline-, glutamic acid-, and leucine-rich protein-1 (PELP1)."
Mol. Endocrinol. 21:1847-1860(2007) [PubMed] [Europe PMC] [Abstract]

"Ubiquitin-interaction motifs of RAP80 are critical in its regulation of estrogen receptor alpha."
Nucleic Acids Res. 35:1673-1686(2007) [PubMed] [Europe PMC] [Abstract]

"ANCCA, an estrogen-regulated AAA+ ATPase coactivator for ERalpha, is required for coregulator occupancy and chromatin modification."
Proc. Natl. Acad. Sci. U.S.A. 104:18067-18072(2007) [PubMed] [Europe PMC] [Abstract]

"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. 216:101-110(2008) [PubMed] [Europe PMC] [Abstract]

"Regulation of estrogen rapid signaling through arginine methylation by PRMT1."
Mol. Cell 31:212-221(2008) [PubMed] [Europe PMC] [Abstract]

"CBP Is a dosage-dependent regulator of nuclear factor-kappaB suppression by the estrogen receptor."
Mol. Endocrinol. 22:263-272(2008) [PubMed] [Europe PMC] [Abstract]

"MTA1-mediated transcriptional repression of BRCA1 tumor suppressor gene."
Oncogene 27:1971-1980(2008) [PubMed] [Europe PMC] [Abstract]

"ERAP75 functions as a coactivator to enhance estrogen receptor alpha transactivation in prostate stromal cells."
Prostate 68:1273-1282(2008) [PubMed] [Europe PMC] [Abstract]

"SH2D4A regulates cell proliferation via the ERalpha/PLC-gamma/PKC pathway."
BMB Rep. 42:516-522(2009) [PubMed] [Europe PMC] [Abstract]

"Regulation of estrogen-dependent transcription by the LIM cofactors CLIM and RLIM in breast cancer."
Cancer Res. 69:128-136(2009) [PubMed] [Europe PMC] [Abstract]

"Functional interaction of DYX1C1 with estrogen receptors suggests involvement of hormonal pathways in dyslexia."
Hum. Mol. Genet. 18:2802-2812(2009) [PubMed] [Europe PMC] [Abstract]

"NF-kappaB and estrogen receptor alpha interactions: Differential function in estrogen receptor-negative and -positive hormone-independent breast cancer cells."
J. Cell. Biochem. 107:448-459(2009) [PubMed] [Europe PMC] [Abstract]

"OTU Domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) deubiquitinates estrogen receptor (ER) alpha and affects ERalpha transcriptional activity."
J. Biol. Chem. 284:16135-16145(2009) [PubMed] [Europe PMC] [Abstract]

"CK1delta modulates the transcriptional activity of ERalpha via AIB1 in an estrogen-dependent manner and regulates ERalpha-AIB1 interactions."
Nucleic Acids Res. 37:3110-3123(2009) [PubMed] [Europe PMC] [Abstract]

"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 28:4053-4064(2009) [PubMed] [Europe PMC] [Abstract]

"The regulation of MS-KIF18A expression and cross talk with estrogen receptor."
PLoS ONE 4:E6407-E6407(2009) [PubMed] [Europe PMC] [Abstract]

"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. 285:31100-31106(2010) [PubMed] [Europe PMC] [Abstract]

"Mammalian MST2 kinase and human Salvador activate and reduce estrogen receptor alpha in the absence of ligand."
J. Mol. Med. 89:181-191(2011) [PubMed] [Europe PMC] [Abstract]

"Splice isoform estrogen receptors as integral transmembrane proteins."
Mol. Biol. Cell 22:4415-4423(2011) [PubMed] [Europe PMC] [Abstract]

"Multiple sequence-specific DNA-binding proteins mediate estrogen receptor signaling through a tethering pathway."
Mol. Endocrinol. 25:564-574(2011) [PubMed] [Europe PMC] [Abstract]

"DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors."
Mol. Biol. Cell 23:188-199(2012) [PubMed] [Europe PMC] [Abstract]

"CBP mediates NF-kappaB-dependent histone acetylation and estrogen receptor recruitment to an estrogen response element in the BIRC3 promoter."
Mol. Cell. Biol. 32:569-575(2012) [PubMed] [Europe PMC] [Abstract]

"CLOCK is a substrate of SUMO and sumoylation of CLOCK upregulates the transcriptional activity of estrogen receptor-alpha."
Oncogene 32:4883-4891(2013) [PubMed] [Europe PMC] [Abstract]

"Modification of ASC1 by UFM1 is crucial for ERalpha transactivation and breast cancer development."
Mol. Cell 56:261-274(2014) [PubMed] [Europe PMC] [Abstract]

"Solution structure of the DNA-binding domain of the oestrogen receptor."
Nature 348:458-461(1990) [PubMed] [Europe PMC] [Abstract]

"The crystal structure of the estrogen receptor DNA-binding domain bound to DNA: how receptors discriminate between their response elements."
Cell 75:567-578(1993) [PubMed] [Europe PMC] [Abstract]

"Molecular basis of agonism and antagonism in the oestrogen receptor."
Nature 389:753-758(1997) [PubMed] [Europe PMC] [Abstract]

"Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains."
Proc. Natl. Acad. Sci. U.S.A. 95:5998-6003(1998) [PubMed] [Europe PMC] [Abstract]

"The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen."
Cell 95:927-937(1998) [PubMed] [Europe PMC] [Abstract]

"Homology model for the ligand-binding domain of the human estrogen receptor."
J. Biomol. Struct. Dyn. 15:841-850(1998) [PubMed] [Europe PMC] [Abstract]

"The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties."
EMBO J. 8:1981-1986(1989) [PubMed] [Europe PMC] [Abstract]

"A transcriptionally active estrogen receptor mutant is a novel type of dominant negative inhibitor of estrogen action."
Mol. Endocrinol. 10:1519-1526(1996) [PubMed] [Europe PMC] [Abstract]

"Screening for ESR mutations in breast and ovarian cancer patients."
Hum. Mutat. 9:531-536(1997) [PubMed] [Europe PMC] [Abstract]

"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. 9:2043-2050(2000) [PubMed] [Europe PMC] [Abstract]

"G protein-coupled receptor 30 expression is up-regulated by EGF and TGF alpha in estrogen receptor alpha-positive cancer cells."
Mol. Endocrinol. 23:1815-1826(2009) [PubMed] [Europe PMC] [Abstract]

"Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas."
Breast Cancer Res. 9:R5-R5(2007) [PubMed] [Europe PMC] [Abstract]

"Delayed puberty and estrogen resistance in a woman with estrogen receptor alpha variant."
N. Engl. J. Med. 369:164-171(2013) [PubMed] [Europe PMC] [Abstract]