MAP3K14

Mitogen-activated protein kinase kinase kinase 14 (MAP3K14), also known as NF-kappa-B-inducing kinase (NIK), is a MAP kinase kinase kinase enzyme that in humans is encoded by the MAP3K14 gene.

MAP3K14
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4DN5, 4G3D, 4IDT, 4IDV
Identifiers
Aliases	MAP3K14, FTDCR1B, HS, HSNIK, NIK, mitogen-activated protein kinase kinase kinase 14
External IDs	OMIM: 604655; MGI: 1858204; HomoloGene: 2940; GeneCards: MAP3K14; OMA:MAP3K14 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) Band 17q21.31 Start 45,263,119 bp End 45,317,029 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 E1|11 66.8 cM Start 103,110,588 bp End 103,158,298 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte gastrocnemius muscle muscle layer of sigmoid colon apex of heart gastric mucosa lymph node tibialis anterior muscle spleen right auricle anterior pituitary Top expressed in granulocyte lumbar spinal ganglion gastrula submandibular gland blood mesenteric lymph nodes muscle of thigh thymus spleen lip More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity protein kinase activity nucleotide binding NF-kappaB-inducing kinase activity protein binding MAP kinase kinase kinase activity ATP binding kinase activity protein serine/threonine kinase activity Cellular component cytoplasm fibrillar center nucleus cytosol intracellular membrane-bounded organelle Biological process phosphorylation tumor necrosis factor-mediated signaling pathway MAPK cascade protein phosphorylation cellular response to mechanical stimulus immune response positive regulation of I-kappaB kinase/NF-kappaB signaling I-kappaB kinase/NF-kappaB signaling NIK/NF-kappaB signaling regulation of mitotic cell cycle signal transduction stress-activated protein kinase signaling cascade activation of protein kinase activity regulation of apoptotic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9020 53859 Ensembl ENSG00000006062 ENSG00000282637 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: 103.11 – 103.16 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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.

Interactions

MAP3K14 has been shown to interact with:

• CHUK,
• IKK2, and
• TRAF2.

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. S2CID 16217708.
• 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. Bibcode:1997PNAS...94.9792S. 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. Bibcode:1997Sci...278..866W. 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. Bibcode:1998PNAS...95.3792L. 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. Bibcode:1998PNAS...95.9319L. 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. doi:10.1128/mcb.18.10.5899. 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. Bibcode:1998Natur.395..292C. doi:10.1038/26254. PMID 9751059. S2CID 4327300.
• 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. S2CID 11305597.
• 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. Bibcode:1999PNAS...96.1042L. 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. doi:10.1128/MCB.19.3.2180. 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. Bibcode:1999Natur.398..252N. doi:10.1038/18465. PMID 10094049. S2CID 4421236.
• 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.