Proteins > Mitogen-activated protein kinase kinase kinase 7
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Mitogen-activated protein kinase kinase kinase 7
A mitogen-activated protein kinase kinase kinase 7 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O43318]
Synonyms
EC 2.7.11.25;
Transforming growth factor-beta-activated kinase 1;
TGF-beta-activated kinase 1
Research
Bioassay Publications (17)
| Timeframe | Studies on this Protein(%) | All Drugs % |
|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 3 (17.65) | 29.6817 |
| 2010's | 13 (76.47) | 24.3611 |
| 2020's | 1 (5.88) | 2.80 |
Compounds (76)
Drugs with Inhibition Measurements
Drugs with Activation Measurements
Discovery of 2,4-1ACS medicinal chemistry letters, , Apr-08, Volume: 12, Issue:4, 2021
ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.European journal of medicinal chemistry, , Jan-01, Volume: 161, 2019
Novel quinazoline derivatives bearing various 6-benzamide moieties as highly selective and potent EGFR inhibitors.Bioorganic & medicinal chemistry, , 05-01, Volume: 26, Issue:8, 2018
Novel LCK/FMS inhibitors based on phenoxypyrimidine scaffold as potential treatment for inflammatory disorders.European journal of medicinal chemistry, , Dec-01, Volume: 141, 2017
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
Synthesis, activity, and pharmacophore development for isatin-beta-thiosemicarbazones with selective activity toward multidrug-resistant cells.Journal of medicinal chemistry, , May-28, Volume: 52, Issue:10, 2009
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD).Bioorganic & medicinal chemistry letters, , Dec-01, Volume: 21, Issue:23, 2011
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
Identification of a selective inhibitor of transforming growth factor β-activated kinase 1 by biosensor-based screening of focused libraries.Bioorganic & medicinal chemistry letters, , 02-15, Volume: 27, Issue:4, 2017
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
Synthesis and anti-tumor activity of imidazopyrazines as TAK1 inhibitors.European journal of medicinal chemistry, , Feb-01, Volume: 163, 2019
Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors.Bioorganic & medicinal chemistry, , 02-15, Volume: 25, Issue:4, 2017
Structure-guided development of covalent TAK1 inhibitors.Bioorganic & medicinal chemistry, , 02-01, Volume: 25, Issue:3, 2017
Discovery of a potent and highly selective transforming growth factor β receptor-associated kinase 1 (TAK1) inhibitor by structure based drug design (SBDD).Bioorganic & medicinal chemistry, , 09-15, Volume: 24, Issue:18, 2016
Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues.Bioorganic & medicinal chemistry, , Nov-01, Volume: 23, Issue:21, 2015
5Z-7-Oxozeaenol covalently binds to MAP2K7 at Cys218 in an unprecedented manner.Bioorganic & medicinal chemistry letters, , Feb-01, Volume: 25, Issue:3, 2015
Oxindole derivatives as inhibitors of TAK1 kinase.Bioorganic & medicinal chemistry letters, , Mar-15, Volume: 21, Issue:6, 2011
Comprehensive analysis of kinase inhibitor selectivity.Nature biotechnology, , Oct-30, Volume: 29, Issue:11, 2011
AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).Blood, , Oct-01, Volume: 114, Issue:14, 2009
Enables
This protein enables 18 target(s):
| Target | Category | Definition |
|---|
| magnesium ion binding | molecular function | Binding to a magnesium (Mg) ion. [GOC:ai] |
| transcription coactivator binding | molecular function | Binding to a transcription coactivator, a protein involved in positive regulation of transcription via protein-protein interactions with transcription factors and other proteins that positively regulate transcription. Transcription coactivators do not bind DNA directly, but rather mediate protein-protein interactions between activating transcription factors and the basal transcription machinery. [GOC:krc] |
| protein serine/threonine kinase activity | molecular function | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate. [GOC:bf, MetaCyc:PROTEIN-KINASE-RXN, PMID:2956925] |
| MAP kinase activity | molecular function | Catalysis of the reaction: protein + ATP = protein phosphate + ADP. This reaction is the phosphorylation of proteins. Mitogen-activated protein kinase; a family of protein kinases that perform a crucial step in relaying signals from the plasma membrane to the nucleus. They are activated by a wide range of proliferation- or differentiation-inducing signals; activation is strong with agonists such as polypeptide growth factors and tumor-promoting phorbol esters, but weak (in most cell backgrounds) by stress stimuli. [GOC:ma, ISBN:0198547684] |
| MAP kinase kinase kinase activity | molecular function | Catalysis of the phosphorylation and activation of a MAP kinase kinase; each MAP kinase kinase can be phosphorylated by any of several MAP kinase kinase kinases. [PMID:9561267] |
| type II transforming growth factor beta receptor binding | molecular function | Binding to a type II transforming growth factor beta receptor. [GOC:ceb, GOC:mah, PMID:11252892] |
| protein binding | molecular function | Binding to a protein. [GOC:go_curators] |
| ATP binding | molecular function | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. [ISBN:0198506732] |
| MAP kinase kinase kinase kinase activity | molecular function | Catalysis of the phosphorylation of serine and threonine residues in a mitogen-activated protein kinase kinase kinase (MAPKKK), resulting in activation of MAPKKK. MAPKKK signaling pathways relay, amplify and integrate signals from the plasma membrane to the nucleus in response to a diverse range of extracellular stimuli. [GOC:bf, PMID:11790549] |
| receptor tyrosine kinase binding | molecular function | Binding to a receptor that possesses protein tyrosine kinase activity. [GOC:mah] |
| ubiquitin protein ligase binding | molecular function | Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins. [GOC:vp] |
| histone kinase activity | molecular function | Catalysis of the transfer of a phosphate group to a histone. [GOC:bf] |
| identical protein binding | molecular function | Binding to an identical protein or proteins. [GOC:jl] |
| scaffold protein binding | molecular function | Binding to a scaffold protein. Scaffold proteins are crucial regulators of many key signaling pathways. Although not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes. [GOC:BHF, GOC:sjp, PMID:10433269, Wikipedia:Scaffold_protein] |
| protein serine kinase activity | molecular function | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate. [RHEA:17989] |
| protein serine/threonine kinase binding | molecular function | Binding to a protein serine/threonine kinase. [GOC:krc, GOC:sl, PMID:28608965] |
| DNA-binding transcription factor binding | molecular function | Binding to a DNA-binding transcription factor, a protein that interacts with a specific DNA sequence (sometimes referred to as a motif) within the regulatory region of a gene to modulate transcription. [GOC:txnOH-2018] |
| linear polyubiquitin binding | molecular function | Binding to a linear polymer of ubiquitin. Linear ubiquitin polymers are formed by linking the amino-terminal methionine (M1) of one ubiquitin molecule to the carboxy-terminal glycine (G76) of the next. [GOC:bf, GOC:PARL, PMID:23453807] |
Located In
This protein is located in 4 target(s):
| Target | Category | Definition |
|---|
| nucleus | cellular component | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. [GOC:go_curators] |
| cytosol | cellular component | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. [GOC:hjd, GOC:jl] |
| plasma membrane | cellular component | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. [ISBN:0716731363] |
| endosome membrane | cellular component | The lipid bilayer surrounding an endosome. [GOC:mah] |
Active In
This protein is active in 2 target(s):
| Target | Category | Definition |
|---|
| cytoplasm | cellular component | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. [ISBN:0198547684] |
| cytosol | cellular component | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. [GOC:hjd, GOC:jl] |
Part Of
This protein is part of 1 target(s):
| Target | Category | Definition |
|---|
| ATAC complex | cellular component | A chromatin remodeling complex that regulates transcription via acetylation primarily of nucleosomal histones H3 and possibly H4. Shares the histone acetylation (HAT) module of GCN5/PCAF-ADA2-ADA3-SGF29 (or orthologs) with the related SAGA complex (GO:0000124). Contains HAT subunits GCN5 or PCAF in a mutually exclusive manner. In addition to the HAT module contains DR1/NC2B, KAT14, MBIP, WDR5, YEATS2 and ZZZ3 or orthologs. Also regulates the activity of non-histone targets and orchestrates mitotic progression by regulating Cyclin A degradation through acetylation. [GOC:bhm, PMID:19936620, PMID:20562830, PMID:28966424] |
Involved In
This protein is involved in 38 target(s):
| Target | Category | Definition |
|---|
| MAPK cascade | biological process | An intracellular protein kinase cascade containing at least a MAP kinase (MAPK). It starts with the activation of a MAP3K, and the consecutive activation of a MPK2K and a MAPK. The cascade can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinase in the downstream tier to transmit a signal within a cell. [PMID:20811974, PMID:9561267] |
| stimulatory C-type lectin receptor signaling pathway | biological process | The series of molecular signals initiated by the binding of C-type lectin to its receptor on the surface of a target cell, and resulting in cellular activation. [GO_REF:0000022, GOC:add, ISBN:0781735149] |
| positive regulation of T cell cytokine production | biological process | Any process that activates or increases the frequency, rate, or extent of T cell cytokine production. [GOC:add] |
| cytoplasmic pattern recognition receptor signaling pathway | biological process | The series of molecular signals initiated by the binding of a ligand from another organism to a cytoplasmic pattern recognition receptor (PRR). PRRs bind pathogen-associated molecular pattern (PAMPs), structures conserved among microbial species. [GOC:add, GOC:ar, ISBN:0781735149, PMID:15199967, PMID:17328678, PMID:18272355, PMID:19531363, PMID:21187438] |
| MyD88-dependent toll-like receptor signaling pathway | biological process | A toll-like receptor signaling pathway in which the MyD88 adaptor molecule mediates transduction of the signal. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate an innate immune response. [GOC:add, ISBN:0781735149, PMID:12467241, PMID:12524386, PMID:12855817, PMID:15585605, PMID:15728447] |
| chromatin remodeling | biological process | A dynamic process of chromatin reorganization resulting in changes to chromatin structure. These changes allow DNA metabolic processes such as transcriptional regulation, DNA recombination, DNA repair, and DNA replication. [GOC:jid, GOC:vw, PMID:12042764, PMID:12697820] |
| inflammatory response | biological process | The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. [GO_REF:0000022, ISBN:0198506732] |
| transforming growth factor beta receptor signaling pathway | biological process | The series of molecular signals initiated by an extracellular ligand binding to a transforming growth factor beta receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:BHF, GOC:mah, GOC:signaling] |
| canonical NF-kappaB signal transduction | biological process | An intracellular signaling cassette characterized by the I-kappaB-kinase (IKK)-dependent activation of NF-kappaB, also known as the canonical NF-kappaB signaling cascade. The cascade begins with activation of a trimeric IKK complex (consisting of catalytic kinase subunits IKKalpha and/or IKKbeta, and the regulatory scaffold protein NEMO) and ends with the regulation of transcription of target genes by NF-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. The canonical NF-kappaB pathway is mainly stimulated by proinflammatory cytokines such as IL-1beta, tumor necrosis factor (TNF)-alpha, antigen ligands, and toll-like receptors (TLRs). [GOC:bf, PMID:12773372, PMID:34659217] |
| I-kappaB phosphorylation | biological process | The process of introducing a phosphate group into an inhibitor of kappa B (I-kappaB) protein. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing bound NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. [GOC:bf, GOC:jl, PMID:21772278, PMID:7594468] |
| JNK cascade | biological process | A MAPK cascade containing at least the JNK (MAPK8) MAP kinase. It starts with the activation of JUN3K (a MAPK3K), which activates JNKK a MAP2K), which in turn activates JNK. The cascade can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinases in the downstream tier. The JNK cascade is activated by stress signals, as well as by G protein-coupled receptors, growth factors, and cytokines, and results in cellular responses such as cell proliferation, cell differentiation, apoptosis and inflammation. [PMID:11790549, PMID:20811974, PMID:23125017] |
| negative regulation of gene expression | biological process | Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). [GOC:txnOH-2018] |
| positive regulation of macroautophagy | biological process | Any process, such as recognition of nutrient depletion, that activates or increases the rate of macroautophagy to bring cytosolic macromolecules to the vacuole/lysosome for degradation. [GOC:go_curators, PMID:9412464] |
| positive regulation of interleukin-2 production | biological process | Any process that activates or increases the frequency, rate, or extent of interleukin-2 production. [GOC:mah] |
| toll-like receptor 3 signaling pathway | biological process | The series of molecular signals initiated by a ligand binding to the endolysosomal toll-like receptor 3. [GOC:add, PMID:16551253, PMID:17328678] |
| toll-like receptor 4 signaling pathway | biological process | The series of molecular signals initiated by a ligand binding to toll-like receptor 4. [GOC:add, PMID:16551253, PMID:17328678] |
| TRIF-dependent toll-like receptor signaling pathway | biological process | The series of molecular signals initiated by a ligand binding to a toll-like receptor where the TRIF adaptor mediates transduction of the signal. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate an innate immune response. [GOC:BHF, PMID:12855817] |
| nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway | biological process | The series of molecular signals initiated by a ligand binding to a nucleotide-binding domain, leucine rich repeat containing receptor (NLR), and ending with the regulation of a downstream cellular process. NLRs are cytoplasmic receptors defined by their tripartite domain architecture that contains: a variable C-terminus, a middle nucleotide-binding domain, and a LRR domain that is variable in the repeats composition and number. [GOC:sj, PMID:18280719, PMID:32838963, PMID:36973360] |
| p38MAPK cascade | biological process | A MAPK cascade containing at least the p38MAPK (MAPK14) MAP kinase, or Hog1 in yeast. It starts with the activation of a MAP3K, and the consecutive activation of a MPK2K and of p38MAPK. The cascade can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinases in the downstream tier. The p38MAPK cascade is activated by stress signals, including hyperosmolarity, as well as by G protein-coupled receptors, growth factors, and cytokines, and results in cellular responses such as cell proliferation, cell differentiation, apoptosis and inflammation. [PMID:20811974, PMID:23125017, PMID:32794416] |
| Fc-epsilon receptor signaling pathway | biological process | The series of molecular signals initiated by the binding of the Fc portion of immunoglobulin E (IgE) to an Fc-epsilon receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. The Fc portion of an immunoglobulin is its C-terminal constant region. [GOC:phg, PMID:12413516, PMID:15048725] |
| interleukin-33-mediated signaling pathway | biological process | The series of molecular signals initiated by interleukin-33 binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:jc, GOC:signaling] |
| interleukin-17A-mediated signaling pathway | biological process | The series of molecular signals initiated by interleukin-17A binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:jc, GOC:signaling] |
| defense response to bacterium | biological process | Reactions triggered in response to the presence of a bacterium that act to protect the cell or organism. [GOC:jl] |
| positive regulation of canonical NF-kappaB signal transduction | biological process | Any process that activates or increases the frequency, rate or extent of a canonical NF-kappaB signaling cascade. [GOC:jl] |
| anoikis | biological process | Apoptosis triggered by inadequate or inappropriate adherence to substrate e.g. after disruption of the interactions between normal epithelial cells and the extracellular matrix. [GOC:jl, http://www.copewithcytokines.de/] |
| positive regulation of JUN kinase activity | biological process | Any process that activates or increases the frequency, rate or extent of JUN kinase activity. [GOC:jl] |
| positive regulation of cell cycle | biological process | Any process that activates or increases the rate or extent of progression through the cell cycle. [GOC:go_curators] |
| positive regulation of cell size | biological process | Any process that increases cell size. [GOC:go_curators] |
| T cell receptor signaling pathway | biological process | The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell. [GOC:add] |
| stress-activated MAPK cascade | biological process | A MAPK cascade that starts with the activation of a stress-activated MAP kinase cascade. [GOC:ai, PMID:15936270] |
| interleukin-1-mediated signaling pathway | biological process | The series of molecular signals initiated by interleukin-1 binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:BHF, GOC:mah, GOC:signaling] |
| cellular response to tumor necrosis factor | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tumor necrosis factor stimulus. [GOC:mah] |
| cellular response to hypoxia | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level. [GOC:mah] |
| positive regulation of non-canonical NF-kappaB signal transduction | biological process | Any process that activates or increases the frequency, rate or extent of the non-canonical NF-kappaB cascade. [GOC:TermGenie] |
| cellular response to angiotensin | biological process | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an angiotensin stimulus. Angiotensin is any of three physiologically active peptides (angiotensin II, III, or IV) processed from angiotensinogen. [GO_REF:0000071, GOC:TermGenie, PMID:22982863] |
| positive regulation of vascular associated smooth muscle cell proliferation | biological process | Any process that activates or increases the frequency, rate or extent of vascular smooth muscle cell proliferation. [GO_REF:0000058, GOC:TermGenie, PMID:23246467] |
| positive regulation of vascular associated smooth muscle cell migration | biological process | Any process that activates or increases the frequency, rate or extent of vascular associated smooth muscle cell migration. [GO_REF:0000058, GOC:BHF, GOC:BHF_miRNA, GOC:rph, GOC:TermGenie, PMID:20693317] |
| immune response | biological process | Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat. [GO_REF:0000022, GOC:add] |