Target Information
Target General Infomation | |||||
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Target ID |
T04361
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Former ID |
TTDNR00706
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Target Name |
Mitogen-activated protein kinase kinase kinase 7
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Gene Name |
MAP3K7
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Synonyms |
TGF-beta-activated kinase 1; Transforming growth factor-beta-activated kinase 1; MAP3K7
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Target Type |
Research
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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. .
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BioChemical Class |
Kinase
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UniProt ID | |||||
EC Number |
EC 2.7.11.25
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Sequence |
MSTASAASSSSSSSAGEMIEAPSQVLNFEEIDYKEIEVEEVVGRGAFGVVCKAKWRAKDV
AIKQIESESERKAFIVELRQLSRVNHPNIVKLYGACLNPVCLVMEYAEGGSLYNVLHGAE PLPYYTAAHAMSWCLQCSQGVAYLHSMQPKALIHRDLKPPNLLLVAGGTVLKICDFGTAC DIQTHMTNNKGSAAWMAPEVFEGSNYSEKCDVFSWGIILWEVITRRKPFDEIGGPAFRIM WAVHNGTRPPLIKNLPKPIESLMTRCWSKDPSQRPSMEEIVKIMTHLMRYFPGADEPLQY PCQYSDEGQSNSATSTGSFMDIASTNTSNKSDTNMEQVPATNDTIKRLESKLLKNQAKQQ SESGRLSLGASRGSSVESLPPTSEGKRMSADMSEIEARIAATTAYSKPKRGHRKTASFGN ILDVPEIVISGNGQPRRRSIQDLTVTGTEPGQVSSRSSSPSVRMITTSGPTSEKPTRSHP WTPDDSTDTNGSDNSIPMAYLTLDHQLQPLAPCPNSKESMAVFEQHCKMAQEYMKVQTEI ALLLQRKQELVAELDQDEKDQQNTSRLVQEHKKLLDENKSLSTYYQQCKKQLEVIRSQQQ KRQGTS |
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Structure |
2EVA; 2YIY; 4GS6; 4L3P; 4L52; 4L53; 4O91
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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 532095 | 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. |
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