MAP3K14

Available structures

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

MGI: 1858204 HomoloGene: 2940 GeneCards: MAP3K14

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 • signal transducer, downstream of receptor, with serine/threonine kinase activity
Cellular component	• cytoplasm • cytosol
Biological process	• phosphorylation • activation of MAPKK activity • T cell costimulation • 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 • signal transduction by protein phosphorylation
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


9020


53859

Ensembl


n/a


ENSMUSG00000020941

UniProt


Q99558


Q9WUL6

RefSeq (mRNA)


NM_003954


NM_016896

RefSeq (protein)


NP_003945.2


NP_058592.1

Location (UCSC)

Chr 17: 45.26 – 45.32 Mb

Chr 11: 103.22 – 103.27 Mb

PubMed search

^[1]

^[2]

Wikidata

View/Edit Human

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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.^[3]^[4]

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.^[4]

Interactions

MAP3K14 has been shown to interact with:

CHUK,^[5]^[6]^[7]^[8]
IKK2,^[5]^[9] and
TRAF2.^[3]^[5]

References

↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
1 2 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.
1 2 "Entrez Gene: MAP3K14 mitogen-activated protein kinase kinase kinase 14".
1 2 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.

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. 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. 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.

Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated Mammalian target of rapamycin EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1

Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1 PDK2 PDK3

Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3

3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4)	BCKDK BCKDHA BCKDHB

(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2 IDH3A IDH3B IDH3G

(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4

Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase Aurora A kinase Aurora B kinase

Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK STK10

Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-

IκB kinase (EC 2.7.11.10)	CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP

cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A PRKACG PRKACB PRKACA PRKY

cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G PRKG1

Protein kinase C (EC 2.7.11.13)	Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3

Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase

Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2

G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4 GRK5 GRK6

Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2 CAMK1 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1

Myosin light-chain kinase (EC 2.7.11.18)	MYLK MYLK2 MYLK3 MYLK4

Phosphorylase kinase (EC 2.7.11.19)	PHKA1 PHKA2 PHKB PHKG1 PHKG2

Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K STK19

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Cyclin-dependent kinase (EC 2.7.11.22)	CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDK12 CDC2L5 PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1

(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5 RPS6KA4 P70S6 kinase P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1

Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14

MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14

Tau-protein kinase (EC 2.7.11.26)	TPK1 TTK GSK-3

(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)	-

Tropomyosin kinase (EC 2.7.11.28)	-

Low-density-lipoprotein receptor kinase (EC 2.7.11.29)	-

Receptor protein serine/threonine kinase (EC 2.7.11.30)	Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

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MAP3K14

Function

Interactions

References

Further reading