Target General Infomation
Target ID
T04361
Former ID
TTDNR00706
Target Name
Mitogen-activated protein kinase kinase kinase 7
Gene Name
MAP3K7
Synonyms
TGF-beta-activated kinase 1; Transforming growth factor-beta-activated kinase 1; MAP3K7
Target Type
Research
Disease Mantle cell lymphoma [ICD9: 200.4, 202.8, 203.0, 208.9; ICD10: C81-C86, C85.7, C90.0, C91-C95]
Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. 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-junN-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 byIKK. 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. .
BioChemical Class
Kinase
UniProt ID
EC Number
EC 2.7.11.25
Sequence
MSTASAASSSSSSSAGEMIEAPSQVLNFEEIDYKEIEVEEVVGRGAFGVVCKAKWRAKDV
AIKQIESESERKAFIVELRQLSRVNHPNIVKLYGACLNPVCLVMEYAEGGSLYNVLHGAE
PLPYYTAAHAMSWCLQCSQGVAYLHSMQPKALIHRDLKPPNLLLVAGGTVLKICDFGTAC
DIQTHMTNNKGSAAWMAPEVFEGSNYSEKCDVFSWGIILWEVITRRKPFDEIGGPAFRIM
WAVHNGTRPPLIKNLPKPIESLMTRCWSKDPSQRPSMEEIVKIMTHLMRYFPGADEPLQY
PCQYSDEGQSNSATSTGSFMDIASTNTSNKSDTNMEQVPATNDTIKRLESKLLKNQAKQQ
SESGRLSLGASRGSSVESLPPTSEGKRMSADMSEIEARIAATTAYSKPKRGHRKTASFGN
ILDVPEIVISGNGQPRRRSIQDLTVTGTEPGQVSSRSSSPSVRMITTSGPTSEKPTRSHP
WTPDDSTDTNGSDNSIPMAYLTLDHQLQPLAPCPNSKESMAVFEQHCKMAQEYMKVQTEI
ALLLQRKQELVAELDQDEKDQQNTSRLVQEHKKLLDENKSLSTYYQQCKKQLEVIRSQQQ
KRQGTS
Structure
2EVA; 2YIY; 4GS6; 4L3P; 4L52; 4L53; 4O91
Inhibitor AZ-TAK1 Drug Info [543552]
compound 17d Drug Info [532095]
NG-25 Drug Info [532902]
Pathways
NetPath Pathway IL5 Signaling Pathway
FSH Signaling Pathway
PANTHER Pathway TGF-beta signaling pathway
Toll receptor signaling pathway
Wnt signaling pathway
p38 MAPK pathway
Pathway Interaction Database BCR signaling pathway
p38 MAPK signaling pathway
Noncanonical Wnt signaling pathway
Presenilin action in Notch and Wnt signaling
IL1-mediated signaling events
TNF receptor signaling pathway
BMP receptor signaling
JNK signaling in the CD4+ TCR pathway
C-MYB transcription factor network
Ephrin B reverse signaling
TGF-beta receptor signaling
Reactome Activation of NF-kappaB in B cells
NOD1/2 Signaling Pathway
FCERI mediated NF-kB activation
Ca2+ pathway
TAK1 activates NFkB by phosphorylation and activation of IKKs complex
Interleukin-1 signaling
activated TAK1 mediates p38 MAPK activation
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
TNFR1-induced NFkappaB signaling pathway
CLEC7A (Dectin-1) signaling
TRAF6 mediated induction of TAK1 complex
WikiPathways Toll-like receptor signaling pathway
DNA Damage Response (only ATM dependent)
TCR Signaling Pathway
Insulin Signaling
p38 MAPK Signaling Pathway
Wnt Signaling Pathway and Pluripotency
MAPK Signaling Pathway
TGF beta Signaling Pathway
IL-6 signaling pathway
FAS pathway and Stress induction of HSP regulation
NLR Proteins
MyD88 cascade initiated on plasma membrane
Cardiac Hypertrophic Response
MAP kinase activation in TLR cascade
MyD88 dependent cascade initiated on endosome
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
Mal cascade initiated on plasma membrane
Fc epsilon receptor (FCERI) signaling
MyD88-independent cascade
Signaling by the B Cell Receptor (BCR)
TAK1 activates NFkB by phosphorylation and activation of IKKs complex
Structural Pathway of Interleukin 1 (IL-1)
EBV LMP1 signaling
TNF alpha Signaling Pathway
B Cell Receptor Signaling Pathway
IL17 signaling pathway
TWEAK Signaling Pathway
RANKL/RANK Signaling Pathway
IL-1 signaling pathway
TCR signaling
Interleukin-1 signaling
Regulation of toll-like receptor signaling pathway
References
Ref 532095Synthesis 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.
Ref 532902Discovery 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.
Ref 543552(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).

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