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Mitogen-activated protein kinase kinase kinase 14
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM604655 MGI1858204 HomoloGene2940 ChEMBL: 5888 GeneCards: MAP3K14 Gene
EC number
RNA expression pattern
PBB GE MAP3K14 205192 at tn.png
More reference expression data
Species Human Mouse
Entrez 9020 53859
Ensembl ENSG00000006062 ENSMUSG00000020941
UniProt Q99558 Q9WUL6
RefSeq (mRNA) NM_003954 NM_016896
RefSeq (protein) NP_003945 NP_058592
Location (UCSC) Chr 17:
43.34 – 43.39 Mb
Chr 11:
103.22 – 103.27 Mb
PubMed search [1] [2]

Mitogen-activated protein kinase kinase kinase 14 also known as NF-kappa-B-inducing kinase (NIK) is an enzyme that in humans is encoded by the MAP3K14 gene.[1][2]


This gene encodes mitogen-activated protein kinase kinase kinase 14, NIK, which is a serine/threonine protein-kinase. This kinase binds to TRAF2 and stimulates NF-κB activity. It is a critical kinase of the alternative NF-κB activation pathway. It shares sequence similarity with several other MAPKK kinases. It participates in an NF-κB-inducing signalling cascade common to receptors of the tumour-necrosis/nerve-growth factor (TNF/NGF) family and to the interleukin-1 type-I receptor.[2]


MAP3K14 has been shown to interact with TRAF2,[1][3] IKK2[3][4] and CHUK.[3][5][6][7]


  1. ^ a b Malinin NL, Boldin MP, Kovalenko AV, Wallach D (March 1997). "MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1". Nature 385 (6616): 540–4. doi:10.1038/385540a0. PMID 9020361. 
  2. ^ a b "Entrez Gene: MAP3K14 mitogen-activated protein kinase kinase kinase 14". 
  3. ^ a b c Luftig, M A; Cahir-McFarland E; Mosialos G; Kieff E (May 2001). "Effects of the NIK aly mutation on NF-kappaB activation by the Epstein-Barr virus latent infection membrane protein, lymphotoxin beta receptor, and CD40". J. Biol. Chem. (United States) 276 (18): 14602–6. doi:10.1074/jbc.C100103200. ISSN 0021-9258. PMID 11278268. 
  4. ^ Woronicz, J D; Gao X; Cao Z; Rothe M; Goeddel D V (October 1997). "IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK". Science (UNITED STATES) 278 (5339): 866–9. doi:10.1126/science.278.5339.866. ISSN 0036-8075. PMID 9346485. 
  5. ^ Régnier, C H; Song H Y; Gao X; Goeddel D V; Cao Z; Rothe M (July 1997). "Identification and characterization of an IkappaB kinase". Cell (UNITED STATES) 90 (2): 373–83. doi:10.1016/S0092-8674(00)80344-X. ISSN 0092-8674. PMID 9244310. 
  6. ^ Xiao, G; Sun S C (July 2000). "Negative regulation of the nuclear factor kappa B-inducing kinase by a cis-acting domain". J. Biol. Chem. (UNITED STATES) 275 (28): 21081–5. doi:10.1074/jbc.M002552200. ISSN 0021-9258. PMID 10887201. 
  7. ^ Ninomiya-Tsuji, J; Kishimoto K; Hiyama A; Inoue J; Cao Z; Matsumoto K (March 1999). "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway". Nature (ENGLAND) 398 (6724): 252–6. doi:10.1038/18465. ISSN 0028-0836. PMID 10094049. 

Further reading[edit]