ER-? may have anti-proliferative effects and therefore oppose the actions of ER-? in reproductive tissue.[4] ER-? may also have an important role in adpative function of the lung during pregnancy.[5]
Tags: DNA-binding proteins, Proteins, Transcription factors
Estrogen-related receptor beta (ERR-beta), also known as NR3B2 (nuclear receptor subfamily 3, group B, member 2), is a nuclear receptor which is encoded by the gene ESRRB (EStrogen Related Receptor Beta).[1] This gene encodes a protein with sequence similarity to the estrogen receptor, a member of nuclear hormone receptor family of steroid hormone receptors. Its function is unknown; however, a similar protein in mouse plays an essential role in placental development.[1]
There are two types of estrogen receptor, ER is a member of the nuclear hormone family of intracellular receptors which is activated by the hormone 17?-estradiol[1] (estrogen), while the estrogen (G protein coupled) receptor GPER is a G-protein coupled receptor. This article refers to the nuclear hormone receptor ER. The main function of the estrogen receptor is as a DNA binding transcription factor which regulates gene expression. However the estrogen receptor also has additional functions independent of DNA binding.[2]
Estrogen receptor beta (ER-beta), also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2), is a nuclear receptor which is activated by the sex hormone estrogen. ER-beta is encoded by the human gene ESR2 (EStrogen Receptor 2). This gene encodes a member of the family of estrogen receptors and 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 17beta-estradiol or related ligands, the encoded protein forms homo- or hetero-dimers that interact with specific DNA sequences to
See also steroid and sex hormone receptors Group A: Estrogen receptor (Sex hormones: Estrogen) 1: Estrogen receptor-? (ER?; NR3A1, ESR1) 2: Estrogen receptor-? (ER?; NR3A2, ESR2) Group B: Estrogen related receptor 1: Estrogen-related receptor-? (ERR?; NR3B1, ESRRA) 2: Estrogen-related receptor-? (ERR?; NR3B2, ESRRB) 3: Estrogen-related receptor-? (ERR?; NR3B3, ESRRG) Group C: 3-Ketosteroid receptors 1: Glucocorticoid receptor (GR; NR3C1) (Cortisol) 2: Mineralocorticoid receptor (MR; NR3C2) (Aldosterone) 3: Progesterone receptor (PR; NR3C3, PGR) (Sex hormones: Progesterone) 4: Androgen receptor (AR; NR3C4, AR) (Sex hormones: Testosterone)
In the absence of hormone, estrogen receptors are largely located in the cytosol. Hormone binding to the receptor triggers a number of events starting with migration of the receptor from the cytosol into the nucleus, dimerization of the receptor, and subsequently binding of the receptor dimer to specific sequences of DNA known as hormone response elements. The DNA/receptor complex then recruits other proteins which are responsible for the transcription of downstream DNA into mRNA and finally protein which results in a change in cell function. Estrogen receptors also occur within the cell nucleus and both estrogen receptor subtypes have a
There are two different forms of the estrogen receptor, usually referred to as ? and ?, each encoded by a separate gene (ESR1 and ESR2 respectively). Hormone activated estrogen receptors form dimers, and since the two forms are coexpressed in many cell types, the receptors may form ER? (??) or ER? (??) homodimers or ER?? (??) heterodimers.[3] Estrogen receptor alpha and beta show significant overall sequence homology, and both are composed of seven domains (listed from the N- to C-terminus; amino acid sequence numbers refer to human ER):Due to alternative RNA splicing, several ER isoforms are known to exist. At
A dramatic demonstration of the importance of estrogens in the regulation of fat deposition comes from transgenic mice that were genetically engineered to lack a functional aromatase gene. These mice have very low levels of estrogen and are obese.[26] Obesity was also observed in estrogen deficient female mice lacking the follicle-stimulating hormone receptor.[27] The effect of low estrogen on increased obesity has been linked to estrogen receptor alpha.[28]
Estrogen receptor alpha (ER-alpha), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is a nuclear receptor which is activated by the sex hormone estrogen. ER-alpha is encoded by the human gene ESR1 (EStrogen Receptor 1).[1][2][3] The estrogen receptor (ESR) is a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription.[4] Alternative splicing results in several ESR1 mRNA transcripts, which differ primarily in their 5-prime untranslated regions. The translated receptors show less variability.[5][1]
The protein encoded by this gene is a nuclear receptor that is closely related to the estrogen receptor. This protein acts as a site-specific transcription regulator and has been also shown to interact with estrogen and the transcription factor TFIIB by direct protein-protein contact. The binding and regulatory activities of this protein have been demonstrated in the regulation of a variety of genes including lactoferrin, osteopontin, medium-chain acyl coenzyme A dehydrogenase (MCAD) and thyroid hormone receptor genes. A processed pseudogene of ESRRA is located on chromosome 13q12.1
Estrogen receptor alpha (ER?) and estrogen related receptor alpha (ERR?) have been found to regulate many of the same genes.[9][10] Furthermore ERR? appears to modulate the activity of ER? in various tissues including breast, uterus, and bone.[11]
The ER's helix 12 domain plays a crucial role in determining interactions with coactivators and corepressors and thereby the respective agonist or antagonist effect of the ligand.[11][12] Different ligands may differ in their affinity for alpha and beta isoforms of the estrogen receptor: 17-beta-estradiol binds equally well to both receptors estrone and raloxifene bind preferentially to the alpha receptor estriol and genistein to the beta receptor Subtype selective estrogen receptor modulators preferentially bind to either the ?- or ?-subtype of the receptor. Additionally, the different estrogen receptor combinations may respond differently to various ligands which may translate into tissue selective agonistic and antagonistic effects.[13] The
Metalloestrogens are a class of inorganic xenoestrogens which can affect the gene expression of human cells responding to estrogen. Effects are related to the physiologic function of estrogen because metalloestrogens have shown affinity for estrogen receptors. Because they can mimic estrogen thus activating the receptor, they are considered harmful and potentially linked with breast cancer.[1] List of metalloestrogens include aluminium, antimony, arsenite, barium, cadmium, chromium (Cr(II)), cobalt, copper, lead, mercury, nickel, selenite, tin and vanadate
Estrogen-related receptor gamma (ERR-gamma), also known as NR3B3 (nuclear receptor subfamily 3, group B, member 3), is a nuclear receptor which is encoded by the gene ESRRG (EStrogen Related Receptor Gamma).[1] This protein is a member of nuclear hormone receptor family of steroid hormone receptors. No physiological activating ligand is known for this orphan receptor, but 4-hydroxytamoxifen and diethylstilbestrol act as inverse agonists and deactivate ESRRG.
Estrogen-related receptor alpha (ERR-alpha), also known as NR3B1 (nuclear receptor subfamily 3, group B, member 1), is a nuclear receptor which is encoded by the gene ESRRA (EStrogen Related Receptor Alpha).[1][
Estrogen receptors were first identified by Elwood V. Jensen at the University of Chicago in the 1950s,[29] for which Jensen was awarded the Lasker Award.[30] The gene for a second estrogen receptor (ER?) was identified in 1996 by Kuiper in rat prostate and ovary using degenerate ERalpha primers.[31]