Estrogen receptor beta

4J26, 1L2J, 1NDE, 1QKM, 1U3Q, 1U3R, 1U3S, 1U9E, 1X76, 1X78, 1X7B, 1X7J, 1YY4, 1YYE, 1ZAF, 2FSZ, 2GIU, 2I0G, 2JJ3, 2NV7, 2QTU, 2YJD, 2YLY, 2Z4B, 3OLL, 3OLS, 3OMO, 3OMP, 3OMQ, 4J24, 4ZI1210013983ENSG00000140009ENSMUSG00000021055Q92731O08537NM_001271877NM_001291712NM_001291723NM_001437NM_010157NM_207707NP_001278652NP_001428NP_034287NP_997590Estrogen receptor beta (ER-β), also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2), is one of two main types of estrogen receptor, a nuclear receptor which is activated by the sex hormone estrogen. In humans, ER-β is encoded by the ESR2 gene.1hj1: RAT ESTROGEN RECEPTOR BETA LIGAND-BINDING DOMAIN IN COMPLEX WITH PURE ANTIESTROGEN ICI164,3841l2j: Human Estrogen Receptor beta Ligand-binding Domain in Complex with (R,R)-5,11-cis-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol1nde: Estrogen Receptor beta with Selective Triazine Modulator1qkm: HUMAN ESTROGEN RECEPTOR BETA LIGAND-BINDING DOMAIN IN COMPLEX WITH PARTIAL AGONIST GENISTEIN1qkn: RAT ESTROGEN RECEPTOR BETA LIGAND-BINDING DOMAIN IN COMPLEX WITH ANTAGONIST RALOXIFENE1u3q: Crystal Structure of Estrogen Receptor beta complexed with CL-2721u3r: Crystal Structure of Estrogen Receptor beta complexed with WAY-3381u3s: Crystal Structure of Estrogen Receptor beta complexed with WAY-7971u9e: CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR BETA COMPLEXED WITH WAY-3971x76: CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR BETA COMPLEXED WITH WAY-6971x78: CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR BETA COMPLEXED WITH WAY-2441x7b: CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR BETA COMPLEXED WITH ERB-0411x7j: CRYSTAL STRUCTURE OF ESTROGEN RECEPTOR BETA COMPLEXED WITH GENISTEIN1yy4: Crystal structure of estrogen receptor beta complexed with 1-chloro-6-(4-hydroxy-phenyl)-naphthalen-2-ol1yye: Crystal structure of estrogen receptor beta complexed with way-2021961zaf: Crystal structure of estrogen receptor beta complexed with 3-Bromo-6-hydroxy-2-(4-hydroxy-phenyl)-inden-1-one2fsz: A second binding site for hydroxytamoxifen within the coactivator-binding groove of estrogen receptor beta2giu: Human estrogen receptor beta ligand-binding domain in complex with compound 452i0g: Benzopyrans are Selective Estrogen Receptor beta Agonists (SERBAs) with Novel Activity in Models of Benign Prostatic Hyperplasia2j7x: STRUCTURE OF ESTRADIOL-BOUND ESTROGEN RECEPTOR BETA LBD IN COMPLEX WITH LXXLL MOTIF FROM NCOA52j7y: STRUCTURE OF 17-EPIESTRIOL-BOUND ESTROGEN RECEPTOR BETA LBD IN COMPLEX WITH LXXLL MOTIF FROM NCOA5 Estrogen receptor beta (ER-β), also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2), is one of two main types of estrogen receptor, a nuclear receptor which is activated by the sex hormone estrogen. In humans, ER-β is encoded by the ESR2 gene. ER-β is a member of the family of estrogen receptors and the superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17-β-estradiol, estriol or related ligands, the encoded protein forms homo-dimers or hetero-dimers with estrogen receptor α that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized. ER-β may have anti-proliferative effects and therefore oppose the actions of ERα in reproductive tissue. ER-β may also have an important role in adaptive function of the lung during pregnancy. ER-β is a potent tumor suppressor and plays a crucial role in many cancer types such as prostate cancer. ER-β is expressed by many tissues including the uterus, blood monocytes and tissue macrophages, colonic and pulmonary epithelial cells and in prostatic epithelium and in malignant counterparts of these tissues. Also, ER-β is found throughout the brain at different concentrations in different neuron clusters. ER-β function is related to various cardiovascular targets including ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein A1 (ApoA-1). Polymorphism may affect ER-β function and lead to altered responses in postmenopausal women receiving hormone replacement therapy. Abnormalities in gene expression associated with ER-β have also been linked to autism spectrum disorder. Mutations in ERβ have been shown to influence cardiomyocytes, the cells that comprise the largest part of the heart, and can lead to an increased risk of cardiovascular disease (CVD). There is a disparity in prevalence of CVD between pre- and post-menopausal women, and the difference can be attributed to estrogen levels. Many types of ERβ receptors exist in order to help regulate gene expression and subsequent health in the body, but binding of 17βE2 (a naturally occurring estrogen) specifically improves cardiac metabolism. The heart utilizes a lot of energy in the form of ATP to properly pump blood and maintain physiological requirements in order to live, and 17βE2 helps by increasing these myocardial ATP levels and respiratory function. In addition, 17βE2 can alter myocardial signaling pathways and stimulate myocyte regeneration, which can aid in inhibiting myocyte cell death. The ERβ signaling pathway plays a role in both vasodilation and arterial dilation, which contributes to an individual having a healthy heart rate and a decrease in blood pressure. This regulation can increase endothelial function and arterial perfusion, both of which are important to myocyte health. Thus, alterations in this signaling pathways due to ERβ mutation could lead to myocyte cell death from physiological stress. While ERα has a more profound role in regeneration after myocyte cell death, ERβ can still help by increasing endothelial progenitor cell activation and subsequent cardiac function. Genetic variation in ERβ is both sex and age dependent and ERβ polymorphism can lead to accelerated brain aging, cognitive impairment, and development of AD pathology. Similar to CVD, post-menopausal women have an increased risk of developing Alzheimer’s disease (AD) due to a loss of estrogen, which affects proper aging of the hippocampus, neural survival and regeneration, and amyloid metabolism. ERβ mRNA is highly expressed in hippocampal formation, an area of the brain that is associated with memory. This expression contributes to increased neuronal survival and helps protect against neurodegenerative diseases such as AD. The pathology of AD is also associated with accumulation of amyloid beta peptide (Aβ). While a proper concentration of Aβ in the brain is important for healthy functioning, too much can lead to cognitive impairment. Thus, ERβ helps control Aβ levels by maintaining the protein it is derived from, β-amyloid precursor protein. ERβ helps by up-regulating insulin-degrading enzyme (IDE), which leads to β-amyloid degradation when accumulation levels begin to rise. However, in AD, lack of ERβ causes a decrease in this degradation and an increase in plaque build-up.