Anti-Estrogen Receptor alpha

Protein function: Nuclear 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. {ECO:0000269, PubMed:10681512, ECO:0000269, PubMed:10816575, ECO:0000269, PubMed:11477071, ECO:0000269, PubMed:11682626, ECO:0000269, PubMed:14764652, ECO:0000269, PubMed:15078875, ECO:0000269, PubMed:15891768, ECO:0000269, PubMed:16043358, ECO:0000269, PubMed:16617102, ECO:0000269, PubMed:16684779, ECO:0000269, PubMed:17922032, ECO:0000269, PubMed:17932106, ECO:0000269, PubMed:18247370, ECO:0000269, PubMed:19350539, ECO:0000269, PubMed:20074560, ECO:0000269, PubMed:20705611, ECO:0000269, PubMed:21330404, ECO:0000269, PubMed:22083956, ECO:0000269, PubMed:7651415, ECO:0000269, PubMed:9328340}. [The UniProt Consortium]