MAP3K14

Mitogen-activated protein kinase kinase kinase 14
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4DN5​, 4G3D​, 4IDT​, 4IDV​
Identifiers
Symbols	MAP3K14 ; FTDCR1B; HS; HSNIK; NIK
External IDs	OMIM: 604655 MGI: 1858204 HomoloGene: 2940 ChEMBL: 5888 GeneCards: MAP3K14 Gene
EC number	2.7.11.25
Gene ontology Molecular function • protein kinase activity • protein serine/threonine kinase activity • NF-kappaB-inducing kinase activity • MAP kinase kinase activity • MAP kinase kinase kinase activity • protein binding • ATP binding Cellular component • cytoplasm • cytosol Biological process • MAPK cascade • activation of MAPKK activity • activation of MAPK activity • stimulatory C-type lectin receptor signaling pathway • immune response • I-kappaB kinase/NF-kappaB signaling • regulation of mitotic cell cycle • signal transduction by protein phosphorylation • stress-activated protein kinase signaling cascade • T cell costimulation • NIK/NF-kappaB signaling • regulation of apoptotic process • positive regulation of I-kappaB kinase/NF-kappaB signaling • innate immune response • cellular response to mechanical stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
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: 45.26 – 45.32 Mb	Chr 11: 103.22 – 103.27 Mb
PubMed search

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]

Function

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]

Interactions

MAP3K14 has been shown to interact with:

• CHUK,^[3][4][5][6]
• IKK2,^[3][7] and
• TRAF2.^[1][3]

References

1. 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. "Entrez Gene: MAP3K14 mitogen-activated protein kinase kinase kinase 14".
3. Luftig MA, 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. 276 (18): 14602–6. doi:10.1074/jbc.C100103200. PMID 11278268.
4. Régnier CH, Song HY, Gao X, Goeddel DV, Cao Z, Rothe M (July 1997). "Identification and characterization of an IkappaB kinase". Cell 90 (2): 373–83. doi:10.1016/S0092-8674(00)80344-X. PMID 9244310.
5. Xiao G, Sun SC (July 2000). "Negative regulation of the nuclear factor kappa B-inducing kinase by a cis-acting domain". J. Biol. Chem. 275 (28): 21081–5. doi:10.1074/jbc.M002552200. PMID 10887201.
6. 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 398 (6724): 252–6. doi:10.1038/18465. PMID 10094049.
7. Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV (October 1997). "IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK". Science 278 (5339): 866–9. doi:10.1126/science.278.5339.866. PMID 9346485.

Further reading

• Régnier CH, Song HY, Gao X, Goeddel DV, Cao Z, Rothe M (1997). "Identification and characterization of an IkappaB kinase". Cell 90 (2): 373–83. doi:10.1016/S0092-8674(00)80344-X. PMID 9244310.
• Song HY, Régnier CH, Kirschning CJ, Goeddel DV, Rothe M (1997). "Tumor necrosis factor (TNF)-mediated kinase cascades: Bifurcation of Nuclear Factor-κB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2". Proc. Natl. Acad. Sci. U.S.A. 94 (18): 9792–6. doi:10.1073/pnas.94.18.9792. PMC 23270. PMID 9275204.
• Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV (1997). "IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK". Science 278 (5339): 866–9. doi:10.1126/science.278.5339.866. PMID 9346485.
• Ling L, Cao Z, Goeddel DV (1998). "NF-κB-inducing kinase activates IKK-α by phosphorylation of Ser-176". Proc. Natl. Acad. Sci. U.S.A. 95 (7): 3792–7. doi:10.1073/pnas.95.7.3792. PMC 19916. PMID 9520446.
• Lee FS, Peters RT, Dang LC, Maniatis T (1998). "MEKK1 activates both IκB kinase α and IκB kinase β". Proc. Natl. Acad. Sci. U.S.A. 95 (16): 9319–24. doi:10.1073/pnas.95.16.9319. PMC 21336. PMID 9689078.
• Lin X, Mu Y, Cunningham ET, Marcu KB, Geleziunas R, Greene WC (1998). "Molecular Determinants of NF-κB-Inducing Kinase Action". Mol. Cell. Biol. 18 (10): 5899–907. PMC 109176. PMID 9742107.
• Cohen L, Henzel WJ, Baeuerle PA (1998). "IKAP is a scaffold protein of the IkappaB kinase complex". Nature 395 (6699): 292–6. doi:10.1038/26254. PMID 9751059.
• Aronsson FC, Magnusson P, Andersson B, Karsten SL, Shibasaki Y, Lendon CL, Goate AM, Brookes AJ (1998). "The NIK protein kinase and C17orf1 genes: chromosomal mapping, gene structures and mutational screening in frontotemporal dementia and parkinsonism linked to chromosome 17". Hum. Genet. 103 (3): 340–5. doi:10.1007/s004390050827. PMID 9799091.
• Nemoto S, DiDonato JA, Lin A (1998). "Coordinate Regulation of IκB Kinases by Mitogen-Activated Protein Kinase Kinase Kinase 1 and NF-κB-Inducing Kinase". Mol. Cell. Biol. 18 (12): 7336–43. doi:10.1128/mcb.18.12.7336. PMC 109315. PMID 9819420.
• Li Y, Kang J, Friedman J, Tarassishin L, Ye J, Kovalenko A, Wallach D, Horwitz MS (1999). "Identification of a cell protein (FIP-3) as a modulator of NF-κB activity and as a target of an adenovirus inhibitor of tumor necrosis factor α-induced apoptosis". Proc. Natl. Acad. Sci. U.S.A. 96 (3): 1042–7. doi:10.1073/pnas.96.3.1042. PMC 15347. PMID 9927690.
• Lallena MJ, Diaz-Meco MT, Bren G, Payá CV, Moscat J (1999). "Activation of IκB Kinase β by Protein Kinase C Isoforms". Mol. Cell. Biol. 19 (3): 2180–8. PMC 84010. PMID 10022904.
• Lin X, Cunningham ET, Mu Y, Geleziunas R, Greene WC (1999). "The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-kappaB acting through the NF-kappaB-inducing kinase and IkappaB kinases". Immunity 10 (2): 271–80. doi:10.1016/S1074-7613(00)80027-8. PMID 10072079.
• Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K (1999). "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway". Nature 398 (6724): 252–6. doi:10.1038/18465. PMID 10094049.
• Delhase M, Hayakawa M, Chen Y, Karin M (1999). "Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation". Science 284 (5412): 309–13. doi:10.1126/science.284.5412.309. PMID 10195894.
• Hu WH, Johnson H, Shu HB (1999). "Tumor necrosis factor-related apoptosis-inducing ligand receptors signal NF-kappaB and JNK activation and apoptosis through distinct pathways". J. Biol. Chem. 274 (43): 30603–10. doi:10.1074/jbc.274.43.30603. PMID 10521444.
• Yamamoto Y, Yin MJ, Gaynor RB (2000). "IκB Kinase α (IKKα) Regulation of IKKβ Kinase Activity". Mol. Cell. Biol. 20 (10): 3655–66. doi:10.1128/MCB.20.10.3655-3666.2000. PMC 85658. PMID 10779355.
• Xiao G, Sun SC (2000). "Negative regulation of the nuclear factor kappa B-inducing kinase by a cis-acting domain". J. Biol. Chem. 275 (28): 21081–5. doi:10.1074/jbc.M002552200. PMID 10887201.
• Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L (2000). "Activation of the NF-kappaB pathway by caspase 8 and its homologs". Oncogene 19 (39): 4451–60. doi:10.1038/sj.onc.1203812. PMID 11002417.
• Kumar A, Eby MT, Sinha S, Jasmin A, Chaudhary PM (2001). "The ectodermal dysplasia receptor activates the nuclear factor-kappaB, JNK, and cell death pathways and binds to ectodysplasin A". J. Biol. Chem. 276 (4): 2668–77. doi:10.1074/jbc.M008356200. PMID 11035039.