Aliases for ESR1 Gene
External Ids for ESR1 Gene
Previous HGNC Symbols for ESR1 Gene
Previous GeneCards Identifiers for ESR1 Gene
This gene encodes an estrogen receptor, a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis. Alternative promoter usage and alternative splicing result in dozens of transcript variants, but the full-length nature of many of these variants has not been determined. [provided by RefSeq, Mar 2014]
GeneCards Summary for ESR1 Gene
ESR1 (Estrogen Receptor 1) is a Protein Coding gene. Diseases associated with ESR1 include estrogen resistance and migraine. Among its related pathways are PI-3K cascade and Signaling by GPCR. GO annotations related to this gene include sequence-specific DNA binding transcription factor activity and chromatin binding. An important paralog of this gene is AR.
UniProtKB/Swiss-Prot for ESR1 Gene
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.
Estrogen controls many cellular processes including growth, differentiation and function of the reproductive system. In females, estrogen's main targets are the ovaries, uterus, vagina and mammary glands. In the male, target organs are the testes, prostate and epididymis. Estrogen is also responsible for the growth and maintenance of the skeleton and the normal functioning of the cardiovascular and nervous systems. Estrogen exerts most of its actions via estrogen receptors (ER). Estrogen receptors are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Today, two estrogen receptors are known, ERalpha and ERbeta. ERalpha protein is highly homologous to ERbeta protein, especially in the DNA and ligand binding domains, although divergence exists in the N-terminal transactivation domain. Both receptors interact with the same DNA response element and show a similar ligand binding profile. Upon ligand binding estrogen receptors undergo a conformational change allowing spontaneous dimerization to form either homo- or heterodimers. As a dimer, the estrogen receptor binds to the estrogen response element (ERE) in the promoter region of target genes. ERalpha and ERbeta which are present in a broad spectrum of tissues.