Liver X Receptor Beta
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Liver X Receptor Beta
Liver X receptor beta (LXR-β) is a member of the nuclear receptor family of transcription factors. LXR-β is encoded by the gene (nuclear receptor subfamily 1, group H, member 2). Function The liver X receptors (LXRs) were originally identified as orphan members of the nuclear receptor superfamily because their ligands were unknown. Like other receptors in the family, LXRs heterodimerize with retinoid X receptor and bind to specific response elements (LXREs) characterized by direct repeats separated by 4 nucleotides. Two genes, alpha ( LXRA) and beta, are known to encode LXR proteins. Structure Crystal structure of human liver X receptor β(LXRβ) forming heterodimer with its partner retinoid X receptor α(RXRα) on its cognate element, an AGGTCA direct repeat spaced by 4 nt shows an extended X-shaped arrangement, with DNA- and ligand-binding domains crossed. The LXRβ core binds DNA via canonical contacts and auxiliary DNA contacts that enhance affinity for the response ele ...
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Nuclear Receptor
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of specific genes thereby controlling the development, homeostasis, and metabolism of the organism. Nuclear receptors bind directly to DNA regulating the expression of adjacent genes; hence these receptors are classified as transcription factors. The regulation of gene expression by nuclear receptors often occurs in the presence of a ligand—a molecule that affects the receptor's behavior. Ligand binding to a nuclear receptor results in a conformational change activating the receptor. The result is up- or down-regulation of gene expression. A unique property of nuclear receptors that differentiates them from other classes of receptors is their direct control of genomic DNA. Nuclear receptors play key roles in both embryonic development a ...
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Transcription Factors
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization (body plan) during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are up to 1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome. TFs work alone or with other proteins in a complex, by promoting (as an activator), or blocking (as a repressor) the recruitment of RNA po ...
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Liver X Receptor
The liver X receptor (LXR) is a member of the nuclear receptor family of transcription factors and is closely related to nuclear receptors such as the PPARs, FXR and RXR. Liver X receptors (LXRs) are important regulators of cholesterol, fatty acid, and glucose homeostasis. LXRs were earlier classified as orphan nuclear receptors, however, upon discovery of endogenous oxysterols as ligands they were subsequently deorphanized. Two isoforms of LXR have been identified and are referred to as LXRα and LXRβ. The liver X receptors are classified into subfamily 1 (thyroid hormone receptor-like) of the nuclear receptor superfamily, and are given the nuclear receptor nomenclature symbols NR1H3 (LXRα) and NR1H2 (LXRβ) respectively. LXRα and LXRβ were discovered separately between 1994-1995. LXRα isoform was independently identified by two groups and initially named RLD-1 and LXR, whereas four groups identified the LXRβ isoform and called it UR, NER, OR-1, and RIP-15. The h ...
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Orphan Receptor
In biochemistry, an orphan receptor is a protein that has a similar structure to other identified receptors but whose endogenous ligand has not yet been identified. If a ligand for an orphan receptor is later discovered, the receptor is referred to as an "adopted orphan". Conversely, the term orphan ligand refers to a biological ligand whose cognate receptor has not yet been identified. Examples Examples of orphan receptors are found in the G protein-coupled receptor (GPCR) and nuclear receptor families. If an endogenous ligand is found, the orphan receptor is "adopted" or "de-orphanized". An example is the nuclear receptor Farnesoid X receptor (FXR) and the GPCR TGR5/GPCR19/G protein-coupled bile acid receptor, both of which are activated by bile acids. Adopted orphan receptors in the nuclear receptor group include FXR, liver X receptor (LXR), and peroxisome proliferator-activated receptor (PPAR). Another example of an orphan receptor site is the PCP binding site in the ...
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Retinoid X Receptor
The retinoid X receptor (RXR) is a type of nuclear receptor that is activated by 9-cis retinoic acid, which is discussed controversially to be of endogenous relevance, and 9-''cis''-13,14-dihydroretinoic acid, which is likely to be the major endogenous mammalian RXR-selective agonist. In a novel review publication, this 9-''cis''-13,14-dihydroretinoic acid was shown to be a metabolite not originating from the known vitamin A (vitamin A1) pathway and its nutritional precursors all-''trans''-retinol ( vitamin A (vitamin A1) or all-''trans''- beta-carotene (provitamin A (provitamin A1)). An independent pathway for generating this endogenous RXR-ligand 9-''cis''-13,14-dihydroretinoic acid from 9-''cis''-13,14-dihydroretinol present in food source and named vitamin A5 or alternatively via provitamin A5 has been suggested as the first novel vitamin identified since 1948, cobalamin / vitamin B12. There are three retinoic X receptors (RXR): RXR-alpha, RXR-beta, and RXR-gamma, en ...
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Response Element
Response elements are short sequences of DNA within a gene Promoter (genetics), promoter or Enhancer (genetics), enhancer region that are able to bind specific transcription factors and regulate Transcription (genetics), transcription of genes. Under conditions of stress, a transcription activator protein binds to the response element and stimulates transcription. If the same response element sequence is located in the control regions of different genes, then these genes will be activated by the same stimuli, thus producing a coordinated response. Hormone response element A hormone response element (HRE) is a short sequence of DNA within the Promoter (biology), promoter of a gene, that is able to bind to a specific hormone receptor complex and therefore regulate Transcription (genetics), transcription. The sequence is most commonly a pair of inverted repeats separated by three nucleotides, which also indicates that the receptor binds as a protein dimer, dimer. Specifically, HRE resp ...
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Liver X Receptor Alpha
Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein that in humans is encoded by the ''NR1H3'' gene (nuclear receptor subfamily 1, group H, member 3). Expression miRNA hsa-miR-613 autoregulates the human LXRα gene by targeting the endogenous LXRα through its specific miRNA response element (613MRE) within the LXRα 3′-untranslated region. LXRα autoregulates its own suppression via induction of SREBP1c which upregulates miRNA has-miR-613. Function The liver X receptors, LXRα (this protein) and LXRβ, form a subfamily of the nuclear receptor superfamily and are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. Additionally, they play an important role in the local activation of thyroid hormones via deiodinases. The inducible LXRα is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRβ is ubiquitously expressed. Ligand-acti ...
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NCOA6
Nuclear receptor coactivator 6 is a protein that in humans is encoded by the ''NCOA6'' gene. Function The protein encoded by this gene is a transcriptional coactivator that can interact with nuclear hormone receptors to enhance their transcriptional activator functions. The encoded protein has been shown to be involved in the hormone-dependent coactivation of several receptors, including prostanoid, retinoid, vitamin D3, thyroid hormone, and steroid receptors. The encoded protein may also act as a general coactivator since it has been shown to interact with some basal transcription factors, histone acetyltransferases, and methyltransferases. Interactions NCOA6 has been shown to interact with: * ASCL2 and * Activating transcription factor 2, * Androgen receptor, * CREB-binding protein, * DNA-PKcs, * E2F1, * EP300, * Estrogen receptor alpha, * Estrogen receptor beta, * HBXIP, * HIST2H3C, * HSF1, * Ku70, * Ku80, * Liver X receptor beta, * MLL3, * RBBP5, * Reti ...
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Retinoid X Receptor Alpha
Retinoid X receptor alpha (RXR-alpha), also known as NR2B1 (nuclear receptor subfamily 2, group B, member 1) is a nuclear receptor that in humans is encoded by the ''RXRA'' gene. Function Retinoid X receptors (RXRs) and retinoic acid receptors (RARs), are nuclear receptors that mediate the biological effects of retinoids by their involvement in retinoic acid-mediated gene activation. These receptors exert their action by binding, as homodimers or heterodimers, to specific sequences in the promoters of target genes and regulating their transcription. The protein encoded by this gene is a member of the steroid and thyroid hormone receptor superfamily of transcription factors. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coa ...
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Intracellular Receptors
Intracellular receptors are Globular protein receptors located inside the cell rather than on its cell membrane. The word ''intracellular'' means "within or inside a cell". Molecules that cross a cell membrane to bind with a receptor are generally nonpolar and may be relatively small. These molecules are also known as ligands. Hormones that use intracellular receptors include thyroid, aldosterone, and steroid hormones. Examples are the class of nuclear receptors located in the cell nucleus and cytoplasm and the IP3 receptor located on the endoplasmic reticulum. The ligands that bind to them are usually intracellular second messengers like inositol trisphosphate (IP3) and extracellular lipophilic hormones like steroid hormones. Some intracrine peptide hormones also have intracellular receptors. Examples * transcription factors ** nuclear receptors * other ** Sigma1 (neurosteroids) ** IP3 receptor (inositol triphosphate, IP3) See also * Receptor * Steroid hormone A ster ...
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