NF-AT
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NF-AT
Nuclear factor of activated T-cells (NFAT) is a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system. NFAT is also involved in the development of cardiac, skeletal muscle, and nervous systems. NFAT was first discovered as an activator for the transcription of IL-2 in T cells (as a regulator of T cell immune response) but has since been found to play an important role in regulating many more body systems. NFAT transcription factors are involved in many normal body processes as well as in development of several diseases, such as inflammatory bowel diseases and several types of cancer. NFAT is also being investigated as a drug target for several different disorders. Family members The NFAT transcription factor family consists of five members NFATc1, NFATc2, NFATc3, NFATc4, and NFAT5. NFATc1 through NFATc4 are regulated by calcium signalling, and are known as the class ...
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NFATC1
Nuclear factor of activated T-cells, cytoplasmic 1 is a protein that in humans is encoded by the ''NFATC1'' gene. Function The product of this gene is a component of the nuclear factor of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation, and an inducible nuclear component. Proteins belonging to this family of transcription factors play a central role in inducible gene transcription during immune response. The product of this gene is an inducible nuclear component. It functions as a major molecular target for the immunosuppressive drugs such as ciclosporin. Five transcript variants encoding distinct isoforms have been identified for this gene. Different isoforms of this protein may regulate inducible expression of different cytokine genes. Interactions NFATC1 has been shown to interact with PIM1. See also * NFAT Nu ...
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NFATC2
Nuclear factor of activated T-cells, cytoplasmic 2 is a protein that in humans is encoded by the ''NFATC2'' gene. Function This gene is a member of the nuclear factor of activated T cells (NFAT) family. The product of this gene is a DNA-binding protein with a REL-homology region (RHR) and an NFAT-homology region (NHR). This protein is present in the cytosol and only translocates to the nucleus upon T cell receptor (TCR) stimulation, where it becomes a member of the nuclear factors of activated T cells transcription complex. This complex plays a central role in inducing gene transcription during the immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. Clinical significance Translocation forming an in frame fusions product between EWSR1 gene and the NFATc2 gene has been described in bone tumor with a Ewing sarcoma-like clinical appearance. The translocation breakpoint led to the loss of the controlling elements of t ...
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NFATC3
Nuclear factor of activated T-cells, cytoplasmic 3 is a protein that in humans is encoded by the ''NFATC3'' gene. Function The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family participate to form this complex also. The product of this gene plays a role in the regulation of gene expression in T cells and immature thymocytes. Four transcript variants encoding distinct isoforms have been identified for this gene. See also * NFAT Nuclear factor of activated T-cells (NFAT) is a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system. NFAT is also involved in the developme ... References Furth ...
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NFATC4
Nuclear factor of activated T-cells, cytoplasmic 4 is a protein that in humans is encoded by the ''NFATC4'' gene. Function The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family of nuclear factors of activated T cells also participate in the formation of this complex. The product of this gene plays a role in the inducible expression of cytokine genes in T cells, especially in the induction of the IL-2 and IL-4. Interactions NFATC4 has been shown to interact with CREB-binding protein. See also * NFAT Nuclear factor of activated T-cells (NFAT) is a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the im ...
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NFAT5
Nuclear factor of activated T-cells 5, also known as NFAT5 and sometimes TonEBP, is a human gene that encodes a transcription factor that regulates the expression of genes involved in the osmotic stress. The product of this gene is a member of the nuclear factors of activated T cells (NFAT) family of transcription factors. Proteins belonging to this family play a central role in inducible gene transcription during the immune response. This protein regulates gene expression induced by osmotic stress in mammalian cells. Unlike monomeric members of this protein family, this protein exists as a homodimer and forms stable dimers with DNA elements. Multiple transcript variants encoding different isoforms have been found for this gene. Osmotic stress Tissues that comprise the kidneys, skin, and eyes are often subjected to osmotic stresses. When the extracellular environment is hypertonic, cells lose water and consequently, shrink. To counteract this, cells increase their sodium uptake ...
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Casein Kinase 1
The Casein kinase 1 family () of protein kinases are serine/threonine-selective enzymes that function as regulators of signal transduction pathways in most eukaryotic cell types. CK1 isoforms are involved in Wnt signaling, circadian rhythms, nucleo-cytoplasmic shuttling of transcription factors, DNA repair, and DNA transcription. Discovery By the early 1950s it was known from metabolic labeling studies using radioactive phosphate that phosphate groups attached to phosphoproteins inside cells can sometimes undergo rapid exchange of new phosphate for old. In order to perform experiments that would allow isolation and characterization of the enzymes involved in attaching and removing phosphate from proteins, there was a need for convenient Substrate (biochemistry), substrates for protein kinases and phosphatase, protein phosphatases. Casein has been used as a substrate since the earliest days of research on protein phosphorylation. By the late 1960s, CAMP-dependent protein kinase, cycl ...
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Cyclosporine
Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephrotic syndrome, and in organ transplants to prevent rejection. It is also used as eye drops for keratoconjunctivitis sicca (dry eyes). Common side effects include high blood pressure, headache, kidney problems, increased hair growth, and vomiting. Other severe side effects include an increased risk of infection, liver problems, and an increased risk of lymphoma. Blood levels of the medication should be checked to decrease the risk of side effects. Use during pregnancy may result in preterm birth; however, ciclosporin does not appear to cause birth defects. Ciclosporin is believed to work by decreasing the function of lymphocytes. It does this by forming a complex with cyclophilin to block the phosphatase activity of calcineuri ...
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Calcineurin
Calcineurin (CaN) is a calcium and calmodulin dependent serine/threonine protein phosphatase (also known as protein phosphatase 3, and calcium-dependent serine-threonine phosphatase). It activates the T cells of the immune system and can be blocked by drugs. Calcineurin activates nuclear factor of activated T cell cytoplasmic (NFATc), a transcription factor, by dephosphorylating it. The activated NFATc is then translocated into the nucleus, where it upregulates the expression of interleukin 2 (IL-2), which, in turn, stimulates the growth and differentiation of the T cell response. Calcineurin is the target of a class of drugs called calcineurin inhibitors, which include ciclosporin, voclosporin, pimecrolimus and tacrolimus. Structure Calcineurin is a heterodimer of a 61-kD calmodulin-binding catalytic subunit, calcineurin A and a 19-kD Ca2+-binding regulatory subunit, calcineurin B. There are three isozymes of the catalytic subunit, each encoded by a separate gene (PPP3CA, ...
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Interleukin-7 Receptor
The interleukin-7 receptor is a protein found on the surface of cells. It is made up of two different smaller protein chains - i.e. it is a heterodimer, and consists of two subunits, interleukin-7 receptor-α (CD127) and common-γ chain receptor ( CD132). The common-γ chain receptors is shared with various cytokines, including interleukin-2, -4, -9, and -15. Interleukin-7 receptor is expressed on various cell types, including naive and memory T cells and many others. Function Interleukin-7 receptor has been shown to play a critical role in the development of immune cells called lymphocytes - specifically in a process known as V(D)J recombination. This protein is also found to control the accessibility of a region of the genome that contains the T-cell receptor gamma gene, by STAT5 and histone acetylation . Knockout studies in mice suggest that blocking apoptosis is an essential function of this protein during differentiation and activation of T lymphocytes. Functional d ...
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ORAI1
Calcium release-activated calcium channel protein 1 is a calcium selective ion channel that in humans is encoded by the ''ORAI1'' gene. Orai channels play an important role in the activation of T-lymphocytes. The loss of function mutation of Orai1 causes severe combined immunodeficiency (SCID) in humans The mammalian orai family has two additional homologs, Orai2 and Orai3. Orai proteins share no homology with any other ion channel family of any other known proteins. They have 4 transmembrane domains and form hexamers. Structure and function Orai channels are activated upon the depletion of internal calcium stores, which is called the "store-operated" or the "capacitative" mechanism. They are molecular constituents of the "calcium release activated calcium currents" ( ICRAC). Upon activation of phospholipase C by various cell surface receptors, inositol trisphosphate is formed that releases calcium from the endoplasmic reticulum. The decreased calcium concentration in the endopl ...
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Calcium Release Activated Channel
Calcium release-activated channels (CRAC) are specialized plasma membrane Ca2+ ion channels. When calcium ions (Ca2+) are depleted from the endoplasmic reticulum (a major store of Ca2+) of mammalian cells, the CRAC channel is activated to slowly replenish the level of calcium in the endoplasmic reticulum. The Ca2+ Release-activated Ca2+ (CRAC) Channel (CRAC-C) Family (TC# 1.A.52) is a member of the Cation Diffusion Facilitator (CDF) Superfamily. These proteins typically have between 4 and 6 transmembrane α-helical spanners (TMSs). The 4 TMS CRAC channels arose by loss of 2TMSs from 6TMS CDF carriers, an example of ' reverse' evolution'. Homology There are several proteins that belong to the CRAC-C family. A list of the currently classified members of the CRAC-C family can be found in thTransporter Classification Database This classification is based on sequence similarity which also happens to coincide with functional and structural similarities between homologues. Structure ...
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Transcription Factor
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 ...
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