Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT4LIAC)

• DTT Name: Serine/threonine-protein kinase NIK (MAP3K14)
• Synonyms: NIK; NF-kappa-beta-inducing kinase; Mitogen-activated protein kinase kinase kinase 14; HsNIK
• Gene Name: MAP3K14
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Kinase
• UniProt ID: M3K14_HUMAN
• TTD ID: T95736
• EC Number: EC 2.7.11.25
• Sequence:
  MAVMEMACPGAPGSAVGQQKELPKAKEKTPPLGKKQSSVYKLEAVEKSPVFCGKWEILND
  VITKGTAKEGSEAGPAAISIIAQAECENSQEFSPTFSERIFIAGSKQYSQSESLDQIPNN
  VAHATEGKMARVCWKGKRRSKARKKRKKKSSKSLAHAGVALAKPLPRTPEQESCTIPVQE
  DESPLGAPYVRNTPQFTKPLKEPGLGQLCFKQLGEGLRPALPRSELHKLISPLQCLNHVW
  KLHHPQDGGPLPLPTHPFPYSRLPHPFPFHPLQPWKPHPLESFLGKLACVDSQKPLPDPH
  LSKLACVDSPKPLPGPHLEPSCLSRGAHEKFSVEEYLVHALQGSVSSGQAHSLTSLAKTW
  AARGSRSREPSPKTEDNEGVLLTEKLKPVDYEYREEVHWATHQLRLGRGSFGEVHRMEDK
  QTGFQCAVKKVRLEVFRAEELMACAGLTSPRIVPLYGAVREGPWVNIFMELLEGGSLGQL
  VKEQGCLPEDRALYYLGQALEGLEYLHSRRILHGDVKADNVLLSSDGSHAALCDFGHAVC
  LQPDGLGKSLLTGDYIPGTETHMAPEVVLGRSCDAKVDVWSSCCMMLHMLNGCHPWTQFF
  RGPLCLKIASEPPPVREIPPSCAPLTAQAIQEGLRKEPIHRVSAAELGGKVNRALQQVGG
  LKSPWRGEYKEPRHPPPNQANYHQTLHAQPRELSPRAPGPRPAEETTGRAPKLQPPLPPE
  PPEPNKSPPLTLSKEESGMWEPLPLSSLEPAPARNPSSPERKATVPEQELQQLEIELFLN
  SLSQPFSLEEQEQILSCLSIDSLSLSDDSEKNPSKASQSSRDTLSSGVHSWSSQAEARSS
  SWNMVLARGRPTDTPSYFNGVKVQIQSLNGEHLHIREFHRVKVGDIATGISSQIPAAAFS
  LVTKDGQPVRYDMEVPDSGIDLQCTLAPDGSFAWSWRVKHGQLENRP
• Function: Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non-canonical pathway. Could act in a receptor-selective manner. Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  NF-kappa B signaling pathway (hsa04064)
  Apoptosis (hsa04210)
  Osteoclast differentiation (hsa04380)
  C-type lectin receptor signaling pathway (hsa04625)
  T cell receptor signaling pathway (hsa04660)
  TNF signaling pathway (hsa04668)
  Intestinal immune network for IgA production (hsa04672)
  Alcoholic liver disease (hsa04936)
  Epithelial cell signaling in Helicobacter pylori infection (hsa05120)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Epstein-Barr virus infection (hsa05169)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
• Reactome Pathway:
  Dectin-1 mediated noncanonical NF-kB signaling (R-HSA-5607761)
  TNFR2 non-canonical NF-kB pathway (R-HSA-5668541)
  NIK-->noncanonical NF-kB signaling (R-HSA-5676590)
  TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway (R-HSA-5676594)
  CD28 dependent PI3K/Akt signaling (R-HSA-389357)

Molecular Interaction Atlas (MIA) of This DTT

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID23374866C31	DMEZSHI	Discovery agent	N.A.	Investigative	[1]

References

• [1] Inhibiting NF- B-inducing kinase (NIK): discovery, structure-based design, synthesis, structure-activity relationship, and co-crystal structures. Bioorg Med Chem Lett. 2013 Mar 1;23(5):1238-44.