Details of the Target
General Information of Target
| Target ID | LDTP03950 | |||||
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| Target Name | Mitogen-activated protein kinase kinase kinase 8 (MAP3K8) | |||||
| Gene Name | MAP3K8 | |||||
| Gene ID | 1326 | |||||
| Synonyms |
COT; ESTF; Mitogen-activated protein kinase kinase kinase 8; EC 2.7.11.25; Cancer Osaka thyroid oncogene; Proto-oncogene c-Cot; Serine/threonine-protein kinase cot; Tumor progression locus 2; TPL-2 |
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| 3D Structure | ||||||
| Sequence |
MEYMSTGSDNKEEIDLLIKHLNVSDVIDIMENLYASEEPAVYEPSLMTMCQDSNQNDERS
KSLLLSGQEVPWLSSVRYGTVEDLLAFANHISNTAKHFYGQRPQESGILLNMVITPQNGR YQIDSDVLLIPWKLTYRNIGSDFIPRGAFGKVYLAQDIKTKKRMACKLIPVDQFKPSDVE IQACFRHENIAELYGAVLWGETVHLFMEAGEGGSVLEKLESCGPMREFEIIWVTKHVLKG LDFLHSKKVIHHDIKPSNIVFMSTKAVLVDFGLSVQMTEDVYFPKDLRGTEIYMSPEVIL CRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAYPSYLYIIHKQAPPLEDIADDCSPG MRELIEASLERNPNHRPRAADLLKHEALNPPREDQPRCQSLDSALLERKRLLSRKELELP ENIADSSCTGSTEESEMLKRQRSLYIDLGALAGYFNLVRGPPTLEYG |
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| Target Type |
Clinical trial
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| Target Bioclass |
Enzyme
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| Family |
Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
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| Subcellular location |
Cytoplasm
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| Function |
Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the pro-inflammatory 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.
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| TTD ID | ||||||
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Target Site Mutations in Different Cell Lines
Probe(s) Labeling This Target
ABPP Probe
| Probe name | Structure | Binding Site(Ratio) | Interaction ID | Ref | |
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IA-alkyne Probe Info |
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C398(5.67) | LDD1703 | [1] | |
Competitor(s) Related to This Target
The Interaction Atlas With This Target
The Protein(s) Related To This Target
Enzyme
| Protein name | Family | Uniprot ID | |||
|---|---|---|---|---|---|
| Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) | . | Q13526 | |||
Transporter and channel
| Protein name | Family | Uniprot ID | |||
|---|---|---|---|---|---|
| Heat shock protein HSP 90-beta (HSP90AB1) | Heat shock protein 90 family | P08238 | |||
Transcription factor
| Protein name | Family | Uniprot ID | |||
|---|---|---|---|---|---|
| Nuclear factor NF-kappa-B p100 subunit (NFKB2) | . | Q00653 | |||
| Nuclear factor NF-kappa-B p105 subunit (NFKB1) | . | P19838 | |||
Other
| Protein name | Family | Uniprot ID | |||
|---|---|---|---|---|---|
| TNFAIP3-interacting protein 2 (TNIP2) | . | Q8NFZ5 | |||
The Drug(s) Related To This Target
Investigative

