IKK1
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IKK1
Inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK-α) also known as IKK1 or conserved helix-loop-helix ubiquitous kinase (CHUK) is a protein kinase that in humans is encoded by the ''CHUK'' gene. IKK-α is part of the IκB kinase complex that plays an important role in regulating the NF-κB transcription factor. However, IKK-α has many additional cellular targets, and is thought to function independently of the NF-κB pathway to regulate epidermal differentiation. Function NF-κB response IKK-α is a member of the serine/threonine protein kinase family and forms a complex in the cell with IKK-β and NEMO. NF-κB transcription factors are normally held in an inactive state by the inhibitory proteins IκBs. IKK-α and IKK-β phosphorylate the IκB proteins, marking them for degradation via ubiquitination and allowing NF-κB transcription factors to go into the nucleus. Once activated, NF-κB transcription factors regulate genes that are implicated in m ...
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IκB Kinase
The IκB kinase (IkappaB kinase or IKK) is an enzyme complex that is involved in propagating the cellular response to inflammation. The IκB kinase enzyme complex is part of the upstream NF-κB signal transduction cascade. The IκBα (inhibitor of nuclear factor kappa B) protein inactivates the NF-κB transcription factor by masking the nuclear localization signals (NLS) of NF-κB proteins and keeping them sequestered in an inactive state in the cytoplasm. Specifically, IKK phosphorylates the inhibitory IκBα protein. This phosphorylation results in the dissociation of IκBα from NF-κB. NF-κB, which is now free, migrates into the nucleus and activates the expression of at least 150 genes; some of which are anti-apoptotic. Catalyzed reaction In enzymology, an IκB kinase () is an enzyme that catalyzes the chemical reaction: :ATP + IκB protein \rightleftharpoons ADP + IκB phosphoprotein Thus, the two substrates of this enzyme are ATP and IκB protein, whereas its two ...
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NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory. Discovery NF-κB was discovered by Ranjan Sen in the lab of Nobel laureate David Baltimore via its interaction with an 11-base pair sequence in the immunoglobulin light-chain enhancer in B cells. Later work by Alexander Poltorak and Bruno Lemaitre in mice and ''Drosophila'' frui ...
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HDAC9
Histone deacetylase 9 is an enzyme that in humans is encoded by the ''HDAC9'' gene. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene has sequence homology to members of the histone deacetylase family. This gene is orthologous to the Xenopus and mouse MITR genes. The MITR protein lacks the histone deacetylase catalytic domain. It represses MEF2 activity through recruitment of multicomponent corepressor complexes that include CtBP and HDACs. This encoded protein may play a role in hematopoiesis. Multiple alternatively spliced transcripts have been described for this gene but the full-length nature of some of them has not been determined. Histone deacetylase 9 (HDAC9), a member of class II HDACs, regulates a wide variety of normal and abnormal physiological functions. Hi ...
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Protein Kinase
A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a functional change of the target protein ( substrate) by changing enzyme activity, cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. There are two main types of protein kinase. The great majority are serine/threonine kinases, which phosphorylate the hydroxyl groups of serines and threonines in their targets and most of the others are tyrosine kinases, although additional types exist. Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction. Chemical ac ...
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Promoter (genetics)
In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of itself, such as tRNA or rRNA. Promoters are located near the transcription start sites of genes, upstream on the DNA (towards the 5' region of the sense strand). Promoters can be about 100–1000 base pairs long, the sequence of which is highly dependent on the gene and product of transcription, type or class of RNA polymerase recruited to the site, and species of organism. Promoters control gene expression in bacteria and eukaryotes. RNA polymerase must attach to DNA near a gene for transcription to occur. Promoter DNA sequences provide an enzyme binding site. The -10 sequence is TATAAT. -35 sequences are conserved on average, but not in most promoters. Artificial promoters with conserved -10 and -35 elements transcribe more slowly. All D ...
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MAP3K14
Mitogen-activated protein kinase kinase kinase 14 also known as NF-kappa-B-inducing kinase (NIK) is an enzyme that in humans is encoded by the ''MAP3K14'' gene. Function This gene encodes mitogen-activated protein kinase kinase kinase 14, NIK, which is a serine/threonine protein-kinase. This kinase binds to TRAF2 and stimulates NF-κB activity. It is a critical kinase of the alternative NF-κB activation pathway. It shares sequence similarity with several other MAPKK kinases. It participates in an NF-κB-inducing signalling cascade common to receptors of the tumour-necrosis/nerve-growth factor (TNF/ NGF) family and to the interleukin-1 type-I receptor. Interactions MAP3K14 has been shown to interact with: * CHUK, * IKK2, and * TRAF2 TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate wi ...
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IRAK1
Interleukin-1 receptor-associated kinase 1 (IRAK-1) is an enzyme in humans encoded by the ''IRAK1'' gene. IRAK-1 plays an important role in the regulation of the expression of inflammatory genes by immune cells, such as monocytes and macrophages, which in turn help the immune system in eliminating bacteria, viruses, and other pathogens. IRAK-1 is part of the IRAK family consisting of IRAK-1, IRAK-2, IRAK-3, and IRAK-4, and is activated by inflammatory molecules released by signaling pathways during pathogenic attack. IRAK-1 is classified as a kinase enzyme, which regulates pathways in both innate and adaptive immune systems. Structure IRAK-1 contains an N-terminal death domain ( DD), a ProST domain, a centrally located kinase domain, and a C-terminal domain. The DD on IRAK-1 acts as an interaction platform for other DD-containing protein, most notably the adaptor protein myeloid differentiation factor 88, MyD88. The proST domain contains serine, proline, and threonine amino aci ...
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FANCA
Fanconi anaemia, complementation group A, also known as FAA, FACA and FANCA, is a protein which in humans is encoded by the ''FANCA'' gene. It belongs to the Fanconi anaemia complementation group (FANC) family of genes of which 12 complementation groups are currently recognized and is hypothesised to operate as a post-replication repair or a cell cycle checkpoint. FANCA proteins are involved in inter-strand DNA cross-link repair and in the maintenance of normal chromosome stability that regulates the differentiation of haematopoietic stem cells into mature blood cells. Mutations involving the FANCA gene are associated with many somatic and congenital defects, primarily involving phenotypic variations of Fanconi anaemia, aplastic anaemia, and forms of cancer such as squamous cell carcinoma and acute myeloid leukaemia. Function The Fanconi anaemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, and FAN ...
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Beta-catenin
Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene. Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcription. In humans, the CTNNB1 protein is encoded by the ''CTNNB1'' gene. In ''Drosophila'', the homologous protein is called ''armadillo''. β-catenin is a subunit of the cadherin protein complex and acts as an intracellular signal transducer in the Wnt signaling pathway. It is a member of the catenin protein family and homologous to γ-catenin, also known as plakoglobin. Beta-catenin is widely expressed in many tissues. In cardiac muscle, beta-catenin localizes to adherens junctions in intercalated disc structures, which are critical for electrical and mechanical coupling between adjacent cardiomyocytes. Mutations and overexpression of β-catenin are associated with many cancers, including hepatocellular carcinoma, colorectal carcinoma, lun ...
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AKT2
AKT2, also known as RAC-beta serine/threonine-protein kinase, is an enzyme that in humans is encoded by the ''AKT2'' gene. It influences metabolite storage as part of the insulin signal transduction pathway. Function This gene is a putative oncogene encoding a protein belonging to the AKT subfamily of serine/threonine kinases that contain SH2-like (Src homology 2-like) domains. The encoded protein is a general protein kinase capable of phosphorylating several known proteins. AKT2 has important roles in controlling glycogenesis, gluconeogenesis, and glucose transport as part of the insulin signal transduction pathway. Clinical significance The gene was shown to be amplified and overexpressed in 2 of 8 ovarian carcinoma cell lines and 2 of 15 primary ovarian tumors. Overexpression contributes to the malignant phenotype of a subset of human ductal pancreatic cancers. Mice lacking Akt2 have a normal body mass, but display a profound diabetic phenotype, indicating that A ...
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AKT1
RAC(Rho family)-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the ''AKT1'' gene. This enzyme belongs to the AKT subfamily of serine/threonine kinases that contain SH2 (Src homology 2-like) protein domains. It is commonly referred to as PKB, or by both names as "Akt/PKB". Function The serine-threonine protein kinase AKT1 is catalytically inactive in serum-starved primary and immortalized fibroblasts. AKT1 and the related AKT2 are activated by platelet-derived growth factor. The activation is rapid and specific, and it is abrogated by mutations in the pleckstrin homology domain of AKT1. It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a critical mediator of growth factor-induced neuronal survival. Survival factors can suppress apoptosis in a transcription-independent manner by activating the serine/threonine kinase AKT1, which then phosphorylates and inactivates components o ...
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