NLK

Identifiers

NLK, nemo like kinase

External IDs

MGI: 1201387 HomoloGene: 88836 GeneCards: NLK

Gene location (Human)

Chr.	Chromosome 17 (human)^[1]

Band	No data available	Start	28,041,737 bp^[1]
Band	No data available	End	28,196,381 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 11 (mouse)^[2]

Band	No data available	Start	78,567,168 bp^[2]
Band	No data available	End	78,697,373 bp^[2]

Gene ontology
Molecular function	• transferase activity • nucleotide binding • transcription factor binding • metal ion binding • kinase activity • protein binding • ubiquitin protein ligase binding • protein serine/threonine kinase activity • SH2 domain binding • ATP binding • protein kinase activity • magnesium ion binding • MAP kinase activity
Cellular component	• cytosol • nucleoplasm • nucleus • cytoplasm
Biological process	• phosphorylation • protein stabilization • Wnt signaling pathway • transcription, DNA-templated • MAPK cascade • protein autophosphorylation • transforming growth factor beta receptor signaling pathway • Wnt signaling pathway, calcium modulating pathway • regulation of transcription, DNA-templated • negative regulation of Wnt signaling pathway • protein phosphorylation • peptidyl-threonine phosphorylation • regulation of gene expression • serine phosphorylation of STAT protein • intracellular signal transduction
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


51701


18099

Ensembl


ENSG00000087095


ENSMUSG00000017376

UniProt


Q9UBE8


O54949

RefSeq (mRNA)


NM_016231


NM_008702

RefSeq (protein)


NP_057315


NP_032728

Location (UCSC)

Chr 17: 28.04 – 28.2 Mb

Chr 17: 78.57 – 78.7 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Serine/threonine protein kinase NLK is an enzyme that in humans is encoded by the NLK gene.^[5]^[6]^[7] Its name is an abbreviation for Nemo-Like Kinase, Nemo (nmo) being the Drosophila ortholog of the mammalian NLK gene.^[8] This enzyme is a member of the Mitogen-activated protein kinase (MAPK) family, although not explicitly designated as such (it does not even have a numbered MAPK code). It is a highly divergent, atypical member of the MAPK group, lacking most features so characteristic of most mitogen-activated protein kinases (e.g. it does not have the dual phosphorylation motifs of typical MAPKs, and is not phosphorylated by any known MAP2 kinases). Its activation mechanism and downstream targets are still not well characterized.^[9]

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000087095 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000017376 - Ensembl, May 2017
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Brott BK, Pinsky BA, Erikson RL (Mar 1998). "Nlk is a murine protein kinase related to Erk/MAP kinases and localized in the nucleus". Proc Natl Acad Sci U S A. 95 (3): 963–8. PMC 18639 . PMID 9448268. doi:10.1073/pnas.95.3.963.
↑ Kehrer-Sawatzki H, Moschgath E, Maier C, Legius E, Elgar G, Krone W (Jul 2000). "Characterization of the Fugu rubripes NLK and FN5 genes flanking the NF1 (Neurofibromatosis type 1) gene in the 5' direction and mapping of the human counterparts". Gene. 251 (1): 63–71. PMID 10863097. doi:10.1016/S0378-1119(00)00188-8.
↑ "Entrez Gene: NLK nemo-like kinase".
↑ Ishitani T, Ishitani S (January 2013). "Nemo-like kinase, a multifaceted cell signaling regulator". Cell. Signal. 25 (1): 190–7. PMID 23000342. doi:10.1016/j.cellsig.2012.09.017.
↑ Coulombe P, Meloche S (August 2007). "Atypical mitogen-activated protein kinases: structure, regulation and functions". Biochim. Biophys. Acta. 1773 (8): 1376–87. PMID 17161475. doi:10.1016/j.bbamcr.2006.11.001.

Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. PMID 8889548. doi:10.1101/gr.6.9.791.
Volorio S, Simon G, Repetto M, et al. (1999). "Sequencing analysis of forty-eight human image cDNA clones similar to Drosophila mutant protein.". DNA Seq. 9 (5-6): 307–15. PMID 10524757. doi:10.3109/10425179809008469.
Kortenjann M, Wehrle C, Nehls MC, Boehm T (2002). "Only one nemo-like kinase gene homologue in invertebrate and mammalian genomes.". Gene. 278 (1-2): 161–5. PMID 11707333. doi:10.1016/S0378-1119(01)00710-7.
Wistow G, Bernstein SL, Wyatt MK, et al. (2002). "Expressed sequence tag analysis of human retina for the NEIBank Project: retbindin, an abundant, novel retinal cDNA and alternative splicing of other retina-preferred gene transcripts.". Mol. Vis. 8: 196–204. PMID 12107411.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMC 139241 . PMID 12477932. doi:10.1073/pnas.242603899.
Ishitani T, Kishida S, Hyodo-Miura J, et al. (2003). "The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling.". Mol. Cell. Biol. 23 (1): 131–9. PMC 140665 . PMID 12482967. doi:10.1128/MCB.23.1.131-139.2003.
Ishitani T, Ninomiya-Tsuji J, Matsumoto K (2003). "Regulation of lymphoid enhancer factor 1/T-cell factor by mitogen-activated protein kinase-related Nemo-like kinase-dependent phosphorylation in Wnt/beta-catenin signaling.". Mol. Cell. Biol. 23 (4): 1379–89. PMC 141159 . PMID 12556497. doi:10.1128/MCB.23.4.1379-1389.2003.
Yasuda J, Tsuchiya A, Yamada T, et al. (2003). "Nemo-like kinase induces apoptosis in DLD-1 human colon cancer cells.". Biochem. Biophys. Res. Commun. 308 (2): 227–33. PMID 12901858. doi:10.1016/S0006-291X(03)01343-3.
Yasuda J, Yokoo H, Yamada T, et al. (2004). "Nemo-like kinase suppresses a wide range of transcription factors, including nuclear factor-kappaB.". Cancer Sci. 95 (1): 52–7. PMID 14720327. doi:10.1111/j.1349-7006.2004.tb03170.x.
Smit L, Baas A, Kuipers J, et al. (2004). "Wnt activates the Tak1/Nemo-like kinase pathway.". J. Biol. Chem. 279 (17): 17232–40. PMID 14960582. doi:10.1074/jbc.M307801200.
Kanei-Ishii C, Ninomiya-Tsuji J, Tanikawa J, et al. (2004). "Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK.". Genes Dev. 18 (7): 816–29. PMC 387421 . PMID 15082531. doi:10.1101/gad.1170604.
Kanei-Ishii C, Nomura T, Tanikawa J, et al. (2004). "Differential sensitivity of v-Myb and c-Myb to Wnt-1-induced protein degradation.". J. Biol. Chem. 279 (43): 44582–9. PMID 15308626. doi:10.1074/jbc.M407831200.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. PMC 528928 . PMID 15489334. doi:10.1101/gr.2596504.
Kojima H, Sasaki T, Ishitani T, et al. (2005). "STAT3 regulates Nemo-like kinase by mediating its interaction with IL-6-stimulated TGFbeta-activated kinase 1 for STAT3 Ser-727 phosphorylation.". Proc. Natl. Acad. Sci. U.S.A. 102 (12): 4524–9. PMC 555521 . PMID 15764709. doi:10.1073/pnas.0500679102.
Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Res. 16 (1): 55–65. PMC 1356129 . PMID 16344560. doi:10.1101/gr.4039406.
Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.". Cell. 125 (4): 801–14. PMID 16713569. doi:10.1016/j.cell.2006.03.032.
Gohda J, Irisawa M, Tanaka Y, et al. (2007). "HTLV-1 Tax-induced NFkappaB activation is independent of Lys-63-linked-type polyubiquitination.". Biochem. Biophys. Res. Commun. 357 (1): 225–30. PMID 17418100. doi:10.1016/j.bbrc.2007.03.125.

MAP kinase activation
Initiation	Mitogen
MAP kinase kinase kinase (MAP3K or MKKK)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs RAF1 ARAF BRAF KSR1 KSR2) MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7
MAP kinase kinase (MAP2K or MKK)	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7
MAP kinase	Extracellular signal-regulated kinases MAPK1 MAPK3 C-Jun N-terminal kinases MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein kinases MAPK11 MAPK12 MAPK13 MAPK14 ERK5 kinase MAPK7 Atypical MAPKs MAPK4 MAPK6 MAPK15 NLK
Phosphatase	MAPK phosphatase

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

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NLK

References

Further reading