Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJQT60)

DTT Name TGF-beta-activated kinase 1 (MAP3K7)
Synonyms Transforming growth factor-beta-activated kinase 1; TAK1; Mitogen-activated protein kinase kinase kinase 7
Gene Name MAP3K7
DTT Type
Literature-reported target
 [1]
Related Disease
Mature B-cell lymphoma [ICD-11: 2A85]
BioChemical Class
Kinase
UniProt ID
M3K7_HUMAN
TTD ID
T04361
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
EC 2.7.11.25
Sequence
MSTASAASSSSSSSAGEMIEAPSQVLNFEEIDYKEIEVEEVVGRGAFGVVCKAKWRAKDV
AIKQIESESERKAFIVELRQLSRVNHPNIVKLYGACLNPVCLVMEYAEGGSLYNVLHGAE
PLPYYTAAHAMSWCLQCSQGVAYLHSMQPKALIHRDLKPPNLLLVAGGTVLKICDFGTAC
DIQTHMTNNKGSAAWMAPEVFEGSNYSEKCDVFSWGIILWEVITRRKPFDEIGGPAFRIM
WAVHNGTRPPLIKNLPKPIESLMTRCWSKDPSQRPSMEEIVKIMTHLMRYFPGADEPLQY
PCQYSDEGQSNSATSTGSFMDIASTNTSNKSDTNMEQVPATNDTIKRLESKLLKNQAKQQ
SESGRLSLGASRGSSVESLPPTSEGKRMSADMSEIEARIAATTAYSKPKRGHRKTASFGN
ILDVPEIVISGNGQPRRRSIQDLTVTGTEPGQVSSRSSSPSVRMITTSGPTSEKPTRSHP
WTPDDSTDTNGSDNSIPMAYLTLDHQLQPLAPCPNSKESMAVFEQHCKMAQEYMKVQTEI
ALLLQRKQELVAELDQDEKDQQNTSRLVQEHKKLLDENKSLSTYYQQCKKQLEVIRSQQQ
KRQGTS
Function
Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity. Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway.
KEGG Pathway
MAPK signaling pathway (hsa04010 )
NF-kappa B signaling pathway (hsa04064 )
Autophagy - animal (hsa04140 )
AMPK signaling pathway (hsa04152 )
Wnt signaling pathway (hsa04310 )
Osteoclast differentiation (hsa04380 )
Adherens junction (hsa04520 )
Neutrophil extracellular trap formation (hsa04613 )
Toll-like receptor signaling pathway (hsa04620 )
NOD-like receptor signaling pathway (hsa04621 )
RIG-I-like receptor signaling pathway (hsa04622 )
IL-17 signaling pathway (hsa04657 )
T cell receptor signaling pathway (hsa04660 )
TNF signaling pathway (hsa04668 )
Alcoholic liver disease (hsa04936 )
Pathogenic Escherichia coli infection (hsa05130 )
Shigellosis (hsa05131 )
Salmonella infection (hsa05132 )
Yersinia infection (hsa05135 )
Leishmaniasis (hsa05140 )
Toxoplasmosis (hsa05145 )
Hepatitis B (hsa05161 )
Measles (hsa05162 )
Herpes simplex virus 1 infection (hsa05168 )
Epstein-Barr virus infection (hsa05169 )
Human immunodeficiency virus 1 infection (hsa05170 )
Coronavirus disease - COVID-19 (hsa05171 )
Lipid and atherosclerosis (hsa05417 )
Fluid shear stress and atherosclerosis (hsa05418 )
Reactome Pathway
NOD1/2 Signaling Pathway (R-HSA-168638 )
FCERI mediated NF-kB activation (R-HSA-2871837 )
Ca2+ pathway (R-HSA-4086398 )
TAK1 activates NFkB by phosphorylation and activation of IKKs complex (R-HSA-445989 )
Interleukin-1 signaling (R-HSA-446652 )
activated TAK1 mediates p38 MAPK activation (R-HSA-450302 )
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 (R-HSA-450321 )
TNFR1-induced NFkappaB signaling pathway (R-HSA-5357956 )
CLEC7A (Dectin-1) signaling (R-HSA-5607764 )
TRAF6 mediated induction of TAK1 complex (R-HSA-937072 )
Activation of NF-kappaB in B cells (R-HSA-1169091 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
3 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AZ-TAK1 DMD4LGN Mantle cell lymphoma 2A85.5 Investigative [1]
NG-25 DMC48D9 Discovery agent N.A. Investigative [2]
PMID23099093C17d DMWS7O9 Discovery agent N.A. Investigative [3]
------------------------------------------------------------------------------------

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2082).
2 Discovery of type II inhibitors of TGFbeta-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2). J Med Chem. 2015 Jan 8;58(1):183-96.
3 Synthesis and structure-activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKepsilon kinases. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7169-73.