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Thyroid Hormone Receptor
The thyroid hormone receptor (TR) is a type of nuclear receptor that is activated by binding thyroid hormone. TRs act as transcription factors, ultimately affecting the regulation of gene transcription and translation. These receptors also have non-genomic effects that lead to second messenger activation, and corresponding cellular response. Structure There are four domains that are present in all TRs. Two of these, the DNA-binding (DBD) and hinge domains, are involved in the ability of the receptor to bind hormone response elements( HREs). TRs also have a ligand binding domain (LBD) that allows them to bind to thyroid hormone with high affinity. The fourth domain is a transactivation domain which allows the receptor to bind other transcription factors. Function Thyroid hormone receptors play critical roles in the regulation of metabolism, heart rate, and development of organisms. These receptors are typically associated with retinoic acid receptors (RXR), forming heterod ...
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Thyroid Hormone Receptor Alpha
Thyroid hormone receptor alpha (TR-alpha) also known as nuclear receptor subfamily 1, group A, member 1 (NR1A1), is a nuclear receptor protein that in humans is encoded by the ''THRA'' gene. Function The protein encoded by this gene is a nuclear hormone receptor for triiodothyronine. It is one of the several receptors for thyroid hormone, and has been shown to mediate the biological activities of thyroid hormone. Knockout studies in mice suggest that the different receptors, while having certain extent of redundancy, may mediate different functions of thyroid hormone. Alternatively spliced transcript variants encoding distinct isoforms have been reported. Role in pathology Mutations of the THRA gene may cause nongoitrous congenital hypothyroidism-6, a subtype of congenital hypothyroidism. Interactions THR1 has been shown to interact with: * COPS2, * EP300, * ITGB3BP, * MED1, * MED6, * MED12, * MED16, * MEF2A, * NCOA6, * TRIP11, and * UBC The University ...
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Protein Dimer
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has roots meaning "two parts", '' di-'' + '' -mer''. A protein dimer is a type of protein quaternary structure. A protein homodimer is formed by two identical proteins. A protein heterodimer is formed by two different proteins. Most protein dimers in biochemistry are not connected by covalent bonds. An example of a non-covalent heterodimer is the enzyme reverse transcriptase, which is composed of two different amino acid chains. An exception is dimers that are linked by disulfide bridges such as the homodimeric protein NEMO. Some proteins contain specialized domains to ensure dimerization (dimerization domains) and specificity. The G protein-coupled cannabinoid receptors have the ability to form both homo- and heterodimers with several ...
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RNA Polymerase
In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the double-stranded DNA so that one strand of the exposed nucleotides can be used as a template for the synthesis of RNA, a process called transcription. A transcription factor and its associated transcription mediator complex must be attached to a DNA binding site called a promoter region before RNAP can initiate the DNA unwinding at that position. RNAP not only initiates RNA transcription, it also guides the nucleotides into position, facilitates attachment and elongation, has intrinsic proofreading and replacement capabilities, and termination recognition capability. In eukaryotes, RNAP can build chains as long as 2.4 million nucleotides. RNAP produces RNA that, functionally, is either for protein coding, i.e. messenger RNA (mRNA); o ...
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Nuclear Receptor Coactivator 1
The nuclear receptor coactivator 1 (''NCOA1'') is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA1 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA1, in turn, acylates histones, which makes downstream DNA more accessible to transcription. Hence, NCOA1 assists nuclear receptors in the upregulation of DNA expression. NCOA1 is also frequently called steroid receptor coactivator-1 (SRC-1). Interactions Nuclear receptor coactivator 1 possesses a basic helix-loop-helix (bHLH) domain and has been shown to interact with: * Androgen receptor, * C-Fos, * C-jun, * CIITA, * CREB-binding protein, * Cyclin D1, * DDX17, * DDX5 and * Estrogen receptor alpha, * Glucocorticoid receptor, * NFKB1, * PCAF, * PPARGC1A, * Peroxisome proliferator-activated receptor alpha, * SNW1, * STAT3, * STAT6, * TRIP4, and * Thyroid hormone receptor bet ...
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Nuclear Receptor Co-repressor 2
The nuclear receptor co-repressor 2 () is a transcriptional coregulatory protein that contains several nuclear receptor-interacting domains. In addition, NCOR2 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR2 assists nuclear receptors in the down regulation of target gene expression. NCOR2 is also referred to as a silencing mediator for retinoid or thyroid-hormone receptors (SMRT) or T3 receptor-associating cofactor 1 (TRAC-1). Function NCOR2/SMRT is a transcriptional coregulatory protein that contains several modulatory functional domains including multiple autonomous repression domains as well as two or three C-terminal nuclear receptor-interacting domains. NCOR2/SMRT serves as a repressive coregulatory factor (corepressor) for multiple transcription factor pathways. In this regard, NCOR2/SMRT functions as a platform protein, facilitating the recruitment of histone deacetylases to the DNA promoters bound by its interacting transcription factors. ...
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Nuclear Receptor Co-repressor 1
The nuclear receptor co-repressor 1 also known as thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1 (TRAC-1) is a protein that in humans is encoded by the ''NCOR1'' gene. NCOR1 is a transcriptional coregulatory protein which contains several nuclear receptor interacting domains. In addition, NCOR1 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR1 assists nuclear receptors in the down regulation of gene expression. Loss of function of this protein significantly increases the strength and power of mouse muscles. Family It is a member of the family of nuclear receptor corepressors; the other human protein that is a member of that family is Nuclear receptor co-repressor 2.UniProNuclear receptor corepressors familyPage accessed June 26, 2016 Interactions Nuclear receptor co-repressor 1 has been shown to interact with: * Androgen receptor, * CHD1, * Calcitriol receptor * GPS2, * Glucocorticoid receptor, * HDAC3, * HDA ...
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Cofactor (biochemistry)
A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that assist in biochemical transformations. The rates at which these happen are characterized in an area of study called enzyme kinetics. Cofactors typically differ from ligands in that they often derive their function by remaining bound. Cofactors can be divided into two types: inorganic ions and complex organic molecules called coenzymes. Coenzymes are mostly derived from vitamins and other organic essential nutrients in small amounts. (Note that some scientists limit the use of the term "cofactor" for inorganic substances; both types are included here.) Coenzymes are further divided into two types. The first is called a "prosthetic group", which consists of a coenzyme that is tightly (or even covalently) and permanently bound to a protein ...
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Coactivator (genetics)
A coactivator is a type of transcriptional coregulator that binds to an activator (a transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA promoter site or a specific DNA regulatory sequence called an enhancer. Binding of the activator-coactivator complex increases the speed of transcription by recruiting general transcription machinery to the promoter, therefore increasing gene expression. The use of activators and coactivators allows for highly specific expression of certain genes depending on cell type and developmental stage. Some coactivators also have histone acetyltransferase (HAT) activity. HATs form large multiprotein complexes that weaken the association of histones to DNA by acetylating the N-terminal histone tail. This provides more space for the transcription machinery to bind to the promoter, therefore increasing gene expression. Activators are found i ...
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Retinoic Acid
Retinoic acid (used simplified here for all-''trans''-retinoic acid) is a metabolite of vitamin A1 (all-''trans''-retinol) that mediates the functions of vitamin A1 required for growth and development. All-''trans''-retinoic acid is required in chordate animals, which includes all higher animals from fish to humans. During early embryonic development, all-''trans''-retinoic acid generated in a specific region of the embryo helps determine position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages. All-''trans''-retinoic acid (ATRA) is the major occurring retinoic acid, while isomers like 13-''cis''- and 9-''cis''-retinoic acid are also present in much lower levels. The key role of all-''trans''-retinoic acid in embryonic development mediates the high teratogeni ...
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Vitamin A
Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably beta-carotene �-carotene. Vitamin A has multiple functions: it is essential for embryo development and growth, for maintenance of the immune system, and for vision, where it combines with the protein opsin to form rhodopsin the light-absorbing molecule necessary for both low-light ( scotopic vision) and color vision. Vitamin A occurs as two principal forms in foods: A) retinol, found in animal-sourced foods, either as retinol or bound to a fatty acid to become a retinyl ester, and B) the carotenoids alpha-carotene, β-carotene, gamma-carotene, and the xanthophyll beta-cryptoxanthin (all of which contain β-ionone rings) that function as provitamin A in herbivore and omnivore animals which possess the enzymes that cleave and conve ...
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Retinoic Acid
Retinoic acid (used simplified here for all-''trans''-retinoic acid) is a metabolite of vitamin A1 (all-''trans''-retinol) that mediates the functions of vitamin A1 required for growth and development. All-''trans''-retinoic acid is required in chordate animals, which includes all higher animals from fish to humans. During early embryonic development, all-''trans''-retinoic acid generated in a specific region of the embryo helps determine position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages. All-''trans''-retinoic acid (ATRA) is the major occurring retinoic acid, while isomers like 13-''cis''- and 9-''cis''-retinoic acid are also present in much lower levels. The key role of all-''trans''-retinoic acid in embryonic development mediates the high teratogeni ...
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Corepressor
In the field of molecular biology, a corepressor is a molecule that represses the expression of genes. In prokaryotes, corepressors are small molecules whereas in eukaryotes, corepressors are proteins. A corepressor does not directly bind to DNA, but instead indirectly regulates gene expression by binding to repressors. A corepressor downregulates (or represses) the expression of genes by binding to and activating a repressor transcription factor. The repressor in turn binds to a gene's operator sequence (segment of DNA to which a transcription factor binds to regulate gene expression), thereby blocking transcription of that gene. Function Prokaryotes In prokaryotes, the term corepressor is used to denote the activating ligand of a repressor protein. For example, the '' E. coli'' tryptophan repressor (TrpR) is only able to bind to DNA and repress transcription of the ''trp'' operon when its corepressor tryptophan is bound to it. TrpR in the absence of tryptophan is ...
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