General Information of Target

Target ID LDTP03950
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
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MEYMSTGSDNKEEIDLLIKHLNVSDVIDIMENLYASEEPAVYEPSLMTMCQDSNQNDERS
KSLLLSGQEVPWLSSVRYGTVEDLLAFANHISNTAKHFYGQRPQESGILLNMVITPQNGR
YQIDSDVLLIPWKLTYRNIGSDFIPRGAFGKVYLAQDIKTKKRMACKLIPVDQFKPSDVE
IQACFRHENIAELYGAVLWGETVHLFMEAGEGGSVLEKLESCGPMREFEIIWVTKHVLKG
LDFLHSKKVIHHDIKPSNIVFMSTKAVLVDFGLSVQMTEDVYFPKDLRGTEIYMSPEVIL
CRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAYPSYLYIIHKQAPPLEDIADDCSPG
MRELIEASLERNPNHRPRAADLLKHEALNPPREDQPRCQSLDSALLERKRLLSRKELELP
ENIADSSCTGSTEESEMLKRQRSLYIDLGALAGYFNLVRGPPTLEYG
Target Type
Clinical trial
Target Bioclass
Enzyme
Family
Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
Subcellular location
Cytoplasm
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.
TTD ID
T00852
Uniprot ID
P41279
DrugMap ID
TTNM0P7
Ensemble ID
ENST00000263056.6
HGNC ID
HGNC:6860
ChEMBL ID
CHEMBL4899

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
769P SNV: p.W72L .
HCT116 SNV: p.A354T .
JURKAT SNV: p.R288Ter .
NCIH1793 SNV: p.T6P .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IA-alkyne
 Probe Info 
C398(5.67)  LDD1703  [1]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 T cell C398(5.67)  LDD1703  [1]
 LDCM0024  KB05 T cell C398(20.00)  LDD1705  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) . Q13526
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Heat shock protein HSP 90-beta (HSP90AB1) Heat shock protein 90 family P08238
Transcription factor
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Nuclear factor NF-kappa-B p100 subunit (NFKB2) . Q00653
Nuclear factor NF-kappa-B p105 subunit (NFKB1) . P19838
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
TNFAIP3-interacting protein 2 (TNIP2) . Q8NFZ5

The Drug(s) Related To This Target

Investigative
Click To Hide/Show 9 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Isis 116359 Antisense drug D0I1AW
Isis 116360 Antisense drug D0C5VI
Isis 116361 Antisense drug D03JVY
Isis 116362 Antisense drug D0M6ZQ
Isis 116363 Antisense drug D0TQ1F
Isis 116414 Antisense drug D09WUL
8-chloro-quinoline-3-carbonitrile Small molecular drug D03MUZ
Nsc-686549 Small molecular drug D0V0QJ
Tpl2 Kinase Inhibitor Small molecular drug D06KSF

References

1 An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29. doi: 10.1016/j.cell.2020.07.001. Epub 2020 Jul 29.