ESR1
GeneName
ESR1
Summary
ESR1, also known as the estrogen receptor (ER), is a 66kDa nuclear hormone receptor that mediates the effects of estrogens in various tissues, including the breast, uterus, and bone. It functions primarily as a transcription factor, binding to estrogen response elements in target gene promoters to regulate gene expression. ESR1 is found in multiple cellular compartments, including the nucleus, cytoplasm, and plasma membrane, and is involved in chromatin remodelling and transcription regulation. The receptor also interacts with various proteins, such as 14-3-3 proteins and calmodulin, which modulate its activity and stability.
Importance
ESR1 is relevant to: - Breast cancer research, particularly in understanding hormone receptor-positive tumours and developing targeted therapies. - Endocrine disruptor studies, as it mediates the effects of environmental estrogens. - Bone health, given its role in regulating osteoblast and osteoclast activity. - Reproductive health, influencing processes such as mammary gland development and uterine function.
Top Products
For researchers investigating ESR1, we highly recommend the Anti-Estrogen Receptor alpha antibody [E115] - ChIP Grade (ab32063). This top-selling recombinant monoclonal antibody is well-cited, with 207 citations, reflecting its strong reputation in the field. It has been validated in knockout models and is suitable for a variety of applications, including Western blotting (WB), immunohistochemistry (IHC), and chromatin immunoprecipitation (ChIP). This versatility makes it an excellent choice for those seeking reliable detection and analysis of ESR1 in their studies. The Recombinant Human Estrogen Receptor alpha protein ELISA Kit (ab153776) is a reliable option for researchers looking to measure ESR1 with confidence.
Abcam Product Citation Summary
The data indicates a strong focus on the role of ESR1 in various contexts related to mammary tissues and cell lines, particularly in studies involving tamoxifen resistance and luminal cell differentiation. The use of multiple applications, including western blotting and immunohistochemistry, highlights the importance of ESR1 in understanding endocrine resistance and meiotic differentiation in mouse models.
Abcam Product Citation Table
Domain
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The modulating domain, also known as A/B or AF-1 domain has a ligand-independent transactivation function. The C-terminus contains a ligand-dependent transactivation domain, also known as E/F or AF-2 domain which overlaps with the ligand binding domain. AF-1 and AF-2 activate transcription independently and synergistically and act in a promoter- and cell-specific manner. AF-1 seems to provide the major transactivation function in differentiated cells.
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. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity).
Isoform 3
Involved in activation of NOS3 and endothelial nitric oxide production (PubMed:21937726). 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 (PubMed:10970861). Binds to ERE and inhibits isoform 1 (PubMed:10970861).
Involvement in disease
Estrogen resistance
ESTRR
A disorder characterized by partial or complete resistance to estrogens, in the presence of elevated estrogen serum levels. Clinical features include absence of the pubertal growth spurt, delayed bone maturation, unfused epiphyses, reduced bone mineral density, osteoporosis, continued growth into adulthood and very tall adult stature. Glucose intolerance, hyperinsulinemia and lipid abnormalities may also be present.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably enhances transcriptional activity. Self-association induces phosphorylation. Dephosphorylation at Ser-118 by PPP5C inhibits its transactivation activity. Phosphorylated by LMTK3 in vitro.
Glycosylated; contains N-acetylglucosamine, probably O-linked.
Ubiquitinated; regulated by LATS1 via DCAF1 it leads to ESR1 proteasomal degradation (PubMed:21602804, PubMed:28068668). Deubiquitinated by OTUB1 (PubMed:19383985). Ubiquitinated by STUB1/CHIP; in the CA1 hippocampal region following loss of endogenous circulating estradiol (17-beta-estradiol/E2) (By similarity). Ubiquitinated by UBR5, leading to its degradation: UBR5 specifically recognizes and binds ligand-bound ESR1 when it is not associated with coactivators (NCOAs) (PubMed:37478846). In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation (PubMed:37478846).
Dimethylated by PRMT1 at Arg-260. The methylation may favor cytoplasmic localization (PubMed:18657504, PubMed:24498420). Demethylated by JMJD6 at Arg-260 (PubMed:24498420).
Palmitoylated (isoform 3). Not biotinylated (isoform 3).
Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation, but not for signaling mediated by the nuclear hormone receptor.
Sequence Similarities
Belongs to the nuclear hormone receptor family. NR3 subfamily.
Tissue Specificity
Widely expressed (PubMed:10970861). Not expressed in the pituitary gland (PubMed:10970861).
Isoform 3
Widely expressed, however not expressed in the pituitary gland.
Cellular localization
- Isoform 1
- Nucleus
- Cytoplasm
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- A minor fraction is associated with the inner membrane.
- Isoform 3
- Nucleus
- Cytoplasm
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cell membrane
- Single-pass type I membrane protein
- Associated with the inner membrane via palmitoylation (Probable). At least a subset exists as a transmembrane protein with a N-terminal extracellular domain.
- Nucleus
- Golgi apparatus
- Cell membrane
- Colocalizes with ZDHHC7 and ZDHHC21 in the Golgi apparatus where most probably palmitoylation occurs. Associated with the plasma membrane when palmitoylated.
Alternative names
ESR, NR3A1, ESR1, Estrogen receptor, ER, ER-alpha, Estradiol receptor, Nuclear receptor subfamily 3 group A member 1