General Information of Drug Therapeutic Target (DTT) (ID: TTNM0P7)

DTT Name Serine/threonine-protein kinase cot (COT)
Synonyms Tumor progression locus 2; TPL-2; Proto-oncogene c-Cot; Mitogen-activated protein kinase kinase kinase 8; ESTF; Cancer Osaka thyroid oncogene; COT
Gene Name MAP3K8
DTT Type
Literature-reported target
[1]
UniProt ID
M3K8_HUMAN
TTD ID
T00852
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.7.11.25
Sequence
MEYMSTGSDNKEEIDLLIKHLNVSDVIDIMENLYASEEPAVYEPSLMTMCQDSNQNDERS
KSLLLSGQEVPWLSSVRYGTVEDLLAFANHISNTAKHFYGQRPQESGILLNMVITPQNGR
YQIDSDVLLIPWKLTYRNIGSDFIPRGAFGKVYLAQDIKTKKRMACKLIPVDQFKPSDVE
IQACFRHENIAELYGAVLWGETVHLFMEAGEGGSVLEKLESCGPMREFEIIWVTKHVLKG
LDFLHSKKVIHHDIKPSNIVFMSTKAVLVDFGLSVQMTEDVYFPKDLRGTEIYMSPEVIL
CRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAYPSYLYIIHKQAPPLEDIADDCSPG
MRELIEASLERNPNHRPRAADLLKHEALNPPREDQPRCQSLDSALLERKRLLSRKELELP
ENIADSSCTGSTEESEMLKRQRSLYIDLGALAGYFNLVRGPPTLEYG
Function
Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.
KEGG Pathway
MAPK signaling pathway (hsa04010 )
Toll-like receptor signaling pathway (hsa04620 )
T cell receptor signaling pathway (hsa04660 )
TNF signaling pathway (hsa04668 )
Reactome Pathway
MAP3K8 (TPL2)-dependent MAPK1/3 activation (R-HSA-5684264 )
CD28 dependent PI3K/Akt signaling (R-HSA-389357 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
GS-5290 DM9NURZ Inflammatory bowel disease DD72 Phase 1 [2]
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References

1 Cot/Tpl-2 protein kinase as a target for the treatment of inflammatory disease. Curr Top Med Chem. 2009;9(7):611-22.
2 Clinical pipeline report, company report or official report of Gilead