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Estrogen receptor - Wikipedia
"Estrogen receptors (ERs) are a group of proteins found inside and on cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the nuclear receptor family of intracellular receptors, and membrane estrogen receptors (mERs) (GPER (GPR30), ER-X, and Gq-mER), which are mostly G protein-coupled receptors. This article refers to the former (ER).
Once activated by estrogen, the ER is able to translocate into the nucleus and bind to DNA to regulate the activity of different genes (i.e. it is a DNA-binding transcription factor). However, it also has additional functions independent of DNA binding.
As hormone receptors for sex steroids (steroid hormone receptors), ERs, androgen receptors (ARs), and progesterone receptors (PRs) are important in sexual maturation and gestation.
Co-evolution of steroidogenic and steroid-inactivating enzymes and adrenal and sex steroid receptors.
"Receptors for the adrenal and sex steroids arose by a series of gene duplications from an ancestral nuclear receptor in a primitive vertebrate, at least 540 million years ago. Sequence analysis indicates many steroidogenic and steroid-inactivating enzymes, including cytochrome P450s and hydroxysteroid dehydrogenases (HSDs), arose at the same time. The estrogen receptor (ER) appears to be the ancestral steroid receptor."
See also: Amphioxus Gonads .
Motif analysis of amphioxus, lamprey and invertebrate estrogen receptors: toward a better understanding of estrogen receptor evolution.
"The origins of steroid-dependent regulation of the vertebrate estrogen receptor (ER) are poorly understood. We used artificial-intelligence-based software to construct 12 motifs specific to the estrogen-binding domain of ERalpha and ERbeta in land vertebrates and teleosts."
An amphioxus orthologue of the estrogen receptor that does not bind estradiol: insights into estrogen receptor evolution.
"... comparative analysis of extant ERs suggests that the ancestral ER did not bind estradiol and that it gained the ability to be regulated by estradiol specifically in the vertebrate lineage, before lamprey split."
3D model of amphioxus steroid receptor complexed with estradiol.
"An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. "
" The 3D model predicts that mutation of Glu-346 to Gln will increase the affinity of testosterone for amphioxus SR and elucidate the evolution of steroid-binding to nuclear receptors."
Estrogen-dependent transactivation of amphioxus steroid hormone receptor via both estrogen and androgen response elements.
"Estrogen actions are largely mediated through the estrogen receptors (ERs), which are ligand-activated transcription factors. To understand the molecular evolution of sex steroid hormone receptors, we isolated cDNAs encoding two steroid receptors from Japanese amphioxus, Branchiostoma belcheri: an ER ortholog and a ketosteroid receptor (SR) ortholog."