Creative Biogene Creative Biogene
Inquiry
Pages
Products
  1. Home
  2. Search Results for "ESR2"

ESR2

Official Full Name
estrogen receptor 2
Organism
Homo sapiens
GeneID
2100
Background
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 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. [provided by RefSeq, Jul 2008]
Synonyms
Erb; ESRB; ODG8; ESTRB; NR3A2; ER-BETA; ESR-BETA;
Bio Chemical Class
Nuclear hormone receptor
Protein Sequence
MDIKNSPSSLNSPSSYNCSQSILPLEHGSIYIPSSYVDSHHEYPAMTFYSPAVMNYSIPSNVTNLEGGPGRQTTSPNVLWPTPGHLSPLVVHRQLSHLYAEPQKSPWCEARSLEHTLPVNRETLKRKVSGNRCASPVTGPGSKRDAHFCAVCSDYASGYHYGVWSCEGCKAFFKRSIQGHNDYICPATNQCTIDKNRRKSCQACRLRKCYEVGMVKCGSRRERCGYRLVRRQRSADEQLHCAGKAKRSGGHAPRVRELLLDALSPEQLVLTLLEAEPPHVLISRPSAPFTEASMMMSLTKLADKELVHMISWAKKIPGFVELSLFDQVRLLESCWMEVLMMGLMWRSIDHPGKLIFAPDLVLDRDEGKCVEGILEIFDMLLATTSRFRELKLQHKEYLCVKAMILLNSSMYPLVTATQDADSSRKLAHLLNAVTDALVWVIAKSGISSQQQSMRLANLLMLLSHVRHASNKGMEHLLNMKCKNVVPVYDLLLEMLNAHVLRGCKSSITGSECSPAEDSKSKEGSQNPQSQ
Open
Disease
Alzheimer disease, Breast cancer, Cushing syndrome, Hepatitis virus infection, Herpes simplex infection, Hyper-lipoproteinaemia, Indeterminate colitis, Irregularities, Low bone mass disorder, Menopausal disorder, Postoperative inflammation, Prostate cancer, Prostate hyperplasia, Sepsis, Solid tumour/cancer, Thrombocytopenia, Trematode disease, Vasomotor/allergic rhinitis
Approved Drug
4 +
Clinical Trial Drug
9 +
Discontinued Drug
9 +

Cat.No. Product Name Price
Cat.No. Product Name Price
Cat.No. Product Name Price
Cat.No. Product Name Price

Detailed Information

Two important functional elements of this gene's protein output are a C-terminal ligand-binding domain and an N-terminal DNA-binding domain. Among the several cellular compartments ESR2 exists in are the nucleus, cytoplasm, and mitochondria. ESR2 generates homo- or hetero-dimers when interacting with estrogens such as 17beta-estradiol, which interact with particular DNA regions to control transcription. The complexity of estrogen signaling paths is further enhanced by some isoforms of ESR2's known ability to block the activation of other estrogen receptors.

Receptor 2 for Estrogen and Its Function in Cellular Development

A ligand-dependent transcription factor, ESR2 mediates several body physiological effects of estrogens. Like ESR1, also known as ERα, it has a similar ligand-binding affinity and can thereby induce the expression of genes related to different cellular activities. ESR2, for example, can turn on transcription in target gene promoter areas by use of estrogen response elements (EREs). Oestrogen's ability to control cell development, differentiation, and metabolic activities depends mostly on this genetic pathway.

Fascinatingly, some ESR2 isoforms are devoid of ligand-binding capacity and cannot use EREs to turn on genes. These isoforms may help to reduce the activity of other members of the estrogen receptor family, therefore controlling the response to estrogenic signals generally.

Apart from genomic activities, ESR2 can also mediate non-genomic effects, particularly at the plasma membrane, where it interacts with several signaling pathways, including the PI3K/AKT pathway, which is essential for insulin sensitivity and glucose homeostasis.

ESR2 and Its Implications in Glycemic Homeostasis

Glycemic homeostasis is mostly regulated by oestrogen, so changes in oestrogen levels or receptor activity are usually linked with diseases like diabetes mellitus (DM). Research on defective estrogen signaling—especially via ESR2—has revealed how insulin sensitivity and glucose metabolism may be altered.

In women, the intricate link between oestrogen and glycemic control can vary depending on oestrogen levels. For example, postmenopausal women often have more insulin resistance; oestrogen replacement treatment helps to reduce this. Likewise, women with Turner syndrome or polycystic ovarian syndrome (PCOS) show more risk for type 2 diabetes (T2D), partly because of disturbances in oestrogen production. Conversely, high estrogen levels during pregnancy could cause insulin resistance, which would result in gestational diabetes.

Although historically linked with female reproductive health, oestrogen's importance in men has also attracted interest. Male glucose metabolism is under control in part by estrogen and its receptors, particularly ESR2. Studies have connected hyperglycemia and insulin resistance to congenital estrogen insufficiency in men. Additionally found to change fat distribution and lower insulin sensitivity is oestrogen treatment for male-to-female transsexuals. This emphasizes how important balanced estrogen receptor activity is to both sexes in preserving ideal glucose homeostasis.

Molecular Mechanisms of ESR2 Action

Estrogen exerts its effects primarily through two receptors, ESR1 and ESR2, which belong to the nuclear receptor superfamily of transcription factors. These receptors contain several domains that allow them to mediate estrogen-induced gene expression. The N-terminal region contains the activation function (AF-1), while the C-terminal region has the ligand-binding domain (LBD) and a second activation function (AF-2). The ability of ESR2 to recruit co-regulatory proteins and interact with other transcription factors plays a crucial role in its diverse biological effects.

Genomic Mechanisms

ESR2, like ESR1, activates transcription by binding to estrogen response elements (EREs) on the promoter regions of target genes. Both receptors can function as homodimers or heterodimers, interacting with full or half ERE sites in the DNA. This genomic action typically regulates the expression of genes involved in cell proliferation, differentiation, and metabolism. ESR2's affinity for estrogen is similar to that of ESR1, but it is thought to have a distinct pattern of co-regulatory protein recruitment, which can influence the final biological outcome of estrogen signaling.

Non-Genomic Mechanisms

Beyond its genomic effects, ESR2 also mediates rapid non-genomic signaling. At the plasma membrane, ESR2 can activate various signaling pathways, including the PI3K/AKT pathway, which is central to regulating glucose metabolism and insulin sensitivity. The non-genomic action of ESR2 can influence cellular responses that are independent of direct gene transcription, adding a layer of complexity to its function in regulating glucose homeostasis.

ESR2 and GLUT4 Regulation

One of the key proteins involved in glucose metabolism is GLUT4, the insulin-sensitive glucose transporter. The expression of GLUT4 in tissues like skeletal muscle and adipose tissue is essential for glucose uptake, especially after meals. The regulation of GLUT4 expression and its translocation to the plasma membrane is a critical aspect of maintaining blood glucose levels.

Role of ESR2 in GLUT4 Expression

Research has shown that ESR2 can influence the expression of GLUT4 by modulating the transcription of the SLC2A4 gene, which encodes GLUT4. Although the exact mechanisms are still under investigation, it is thought that ESR2 may regulate GLUT4 expression through both genomic and non-genomic pathways. For instance, ESR2 might recruit co-activators that promote the transcription of the SLC2A4 gene, leading to increased GLUT4 expression and improved glucose uptake in muscle and adipose tissues.

Figure 1 shows how SP1 and CEBPA mediate E2-induced ESR1/ESR2 regulation of Slc2a4 transcription.Figure 1. Mechanisms of SP1 and CEBPA in E2-Induced ESR1/ESR2-Mediated Regulation of Slc2a4 Transcription (Gregorio KCR, et al., 2021)

In conditions such as insulin resistance and diabetes, the expression of GLUT4 is often reduced, which contributes to impaired glucose uptake and elevated blood glucose levels. Studies have shown that interventions that increase GLUT4 expression or enhance its translocation to the plasma membrane can improve glycemic control. This underscores the importance of ESR2 in maintaining proper glucose metabolism and its potential as a therapeutic target for insulin resistance and diabetes.

References:

  1. Chantalat E, Valera MC, et al. Estrogen Receptors and Endometriosis. Int J Mol Sci. 2020 Apr 17;21(8):2815.
  2. Wang S, Liu L, et al. Effects of BXSMD on ESR1 and ESR2 expression in CSD female mice. J Ethnopharmacol. 2024 Jan 10;318(Pt B):116973.
  3. Hamilton KJ, Hewitt SC, et al. Estrogen Hormone Biology. Curr Top Dev Biol. 2017;125:109-146.
Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry

Products

Transfected Stable Cell Lines

Premade Virus Particles

Laboratory Equipment

RNA Interference Products

Cell Lysate

Clones

Enzymes

Kits

Aptamers

Services

Stable Cell Line Generation

Target-based Drug Discovery Service

Custom Libraries Construction Service

Microbe Genome Editing Service

Biosafety Testing Service

Nucleotides Service

MicroRNA Service

RNAi Service

Custom Viral Service

Platforms

CRISPR/Cas9 PlatformCB

QvirusTM Platform

IntegrateRNA Platform

Microbiology Platform

Zebrafish Platform

Get in Touch

Tel

Fax

Email

USA

Germany

Copyright © Creative Biogene. All rights reserved.

Privacy Policy | Cookie Policy