NLK_MOUSE
ID NLK_MOUSE Reviewed; 527 AA.
AC O54949; Q5SYE6; Q6PF98;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Serine/threonine-protein kinase NLK;
DE EC=2.7.11.24;
DE AltName: Full=Nemo-like kinase;
GN Name=Nlk {ECO:0000312|EMBL:AAC24499.1};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAC24499.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF
RP LYS-167 AND THR-298.
RC STRAIN=BALB/cJ {ECO:0000312|EMBL:AAC24499.1};
RC TISSUE=Brain {ECO:0000312|EMBL:AAC24499.1};
RX PubMed=9448268; DOI=10.1073/pnas.95.3.963;
RA Brott B.K., Pinsky B.A., Erikson R.L.;
RT "Nlk is a murine protein kinase related to Erk/MAP kinases and localized in
RT the nucleus.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:963-968(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Brain, and Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AUTOPHOSPHORYLATION, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP LYS-167 AND CYS-437.
RX PubMed=10391247; DOI=10.1038/21674;
RA Ishitani T., Ninomiya-Tsuji J., Nagai S., Nishita M., Meneghini M.,
RA Barker N., Waterman M., Bowerman B., Clevers H., Shibuya H., Matsumoto K.;
RT "The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-
RT catenin and transcription factor TCF.";
RL Nature 399:798-802(1999).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=11745377;
RX DOI=10.1002/1521-4141(200112)31:12<3580::aid-immu3580>3.0.co;2-n;
RA Kortenjann M., Nehls M., Smith A.J., Carsetti R., Schuler J., Kohler G.,
RA Boehm T.;
RT "Abnormal bone marrow stroma in mice deficient for nemo-like kinase, Nlk.";
RL Eur. J. Immunol. 31:3580-3587(2001).
RN [6]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=12482967; DOI=10.1128/mcb.23.1.131-139.2003;
RA Ishitani T., Kishida S., Hyodo-Miura J., Ueno N., Yasuda J., Waterman M.,
RA Shibuya H., Moon R.T., Ninomiya-Tsuji J., Matsumoto K.;
RT "The TAK1-NLK mitogen-activated protein kinase cascade functions in the
RT Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling.";
RL Mol. Cell. Biol. 23:131-139(2003).
RN [7]
RP FUNCTION, INTERACTION WITH LEF1 AND TCF7L2, AND MUTAGENESIS OF LYS-167.
RX PubMed=12556497; DOI=10.1128/mcb.23.4.1379-1389.2003;
RA Ishitani T., Ninomiya-Tsuji J., Matsumoto K.;
RT "Regulation of lymphoid enhancer factor 1/T-cell factor by mitogen-
RT activated protein kinase-related Nemo-like kinase-dependent phosphorylation
RT in Wnt/beta-catenin signaling.";
RL Mol. Cell. Biol. 23:1379-1389(2003).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=14720327; DOI=10.1111/j.1349-7006.2004.tb03170.x;
RA Yasuda J., Yokoo H., Yamada T., Kitabayashi I., Sekiya T., Ichikawa H.;
RT "Nemo-like kinase suppresses a wide range of transcription factors,
RT including nuclear factor-kappaB.";
RL Cancer Sci. 95:52-57(2004).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH STAT3.
RX PubMed=15004007; DOI=10.1101/gad.1166904;
RA Ohkawara B., Shirakabe K., Hyodo-Miura J., Matsuo R., Ueno N.,
RA Matsumoto K., Shibuya H.;
RT "Role of the TAK1-NLK-STAT3 pathway in TGF-beta-mediated mesoderm
RT induction.";
RL Genes Dev. 18:381-386(2004).
RN [10] {ECO:0000305}
RP FUNCTION, INTERACTION WITH MYB AND HIPK2, AND MUTAGENESIS OF LYS-167 AND
RP THR-298.
RX PubMed=15082531; DOI=10.1101/gad.1170604;
RA Kanei-Ishii C., Ninomiya-Tsuji J., Tanikawa J., Nomura T., Ishitani T.,
RA Kishida S., Kokura K., Kurahashi T., Ichikawa-Iwata E., Kim Y.,
RA Matsumoto K., Ishii S.;
RT "Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via
RT TAK1, HIPK2, and NLK.";
RL Genes Dev. 18:816-829(2004).
RN [11]
RP FUNCTION, AND INTERACTION WITH MYB.
RX PubMed=15308626; DOI=10.1074/jbc.m407831200;
RA Kanei-Ishii C., Nomura T., Tanikawa J., Ichikawa-Iwata E., Ishii S.;
RT "Differential sensitivity of v-Myb and c-Myb to Wnt-1-induced protein
RT degradation.";
RL J. Biol. Chem. 279:44582-44589(2004).
RN [12]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH MYBL1 AND MYBL2, AND
RP MUTAGENESIS OF LYS-167.
RX PubMed=16055500; DOI=10.1091/mbc.e05-05-0470;
RA Kurahashi T., Nomura T., Kanei-Ishii C., Shinkai Y., Ishii S.;
RT "The Wnt-NLK signaling pathway inhibits A-Myb activity by inhibiting the
RT association with coactivator CBP and methylating histone H3.";
RL Mol. Biol. Cell 16:4705-4713(2005).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH MEF2A.
RX PubMed=17785444; DOI=10.1128/mcb.01481-07;
RA Satoh K., Ohnishi J., Sato A., Takeyama M., Iemura S., Natsume T.,
RA Shibuya H.;
RT "Nemo-like kinase-myocyte enhancer factor 2A signaling regulates anterior
RT formation in Xenopus development.";
RL Mol. Cell. Biol. 27:7623-7630(2007).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [15]
RP FUNCTION, AND INTERACTION WITH E3 UBIQUITIN-PROTEIN LIGASE COMPLEXES.
RX PubMed=18765672; DOI=10.1074/jbc.m804340200;
RA Kanei-Ishii C., Nomura T., Takagi T., Watanabe N., Nakayama K.I., Ishii S.;
RT "Fbxw7 acts as an E3 ubiquitin ligase that targets c-Myb for nemo-like
RT kinase (NLK)-induced degradation.";
RL J. Biol. Chem. 283:30540-30548(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-298, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [17]
RP FUNCTION, AUTOPHOSPHORYLATION, INTERACTION WITH MAP3K7 AND TAB2, AND
RP MUTAGENESIS OF LYS-167.
RX PubMed=20194509; DOI=10.1074/jbc.m109.083246;
RA Li M., Wang H., Huang T., Wang J., Ding Y., Li Z., Zhang J., Li L.;
RT "TAB2 scaffolds TAK1 and NLK in repressing canonical Wnt signaling.";
RL J. Biol. Chem. 285:13397-13404(2010).
RN [18]
RP FUNCTION, INTERACTION WITH NOTCH1, AND MUTAGENESIS OF LYS-167.
RX PubMed=20118921; DOI=10.1038/ncb2028;
RA Ishitani T., Hirao T., Suzuki M., Isoda M., Ishitani S., Harigaya K.,
RA Kitagawa M., Matsumoto K., Itoh M.;
RT "Nemo-like kinase suppresses Notch signalling by interfering with formation
RT of the Notch active transcriptional complex.";
RL Nat. Cell Biol. 12:278-285(2010).
RN [19]
RP FUNCTION, AND INTERACTION WITH FOXO4.
RX PubMed=20874444; DOI=10.1089/ars.2010.3243;
RA Szypowska A.A., de Ruiter H., Meijer L.A.T., Smits L.M.M.,
RA Burgering B.M.T.;
RT "Oxidative stress-dependent regulation of Forkhead box O4 activity by nemo-
RT like kinase.";
RL Antioxid. Redox Signal. 14:563-578(2011).
RN [20]
RP FUNCTION, AUTOPHOSPHORYLATION, ACTIVITY REGULATION, HOMODIMERIZATION,
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-298, AND MUTAGENESIS OF
RP LYS-167; THR-298 AND CYS-437.
RX PubMed=21118996; DOI=10.1091/mbc.e10-07-0605;
RA Ishitani S., Inaba K., Matsumoto K., Ishitani T.;
RT "Homodimerization of Nemo-like kinase is essential for activation and
RT nuclear localization.";
RL Mol. Biol. Cell 22:266-277(2011).
CC -!- FUNCTION: Serine/threonine-protein kinase that regulates a number of
CC transcription factors with key roles in cell fate determination.
CC Positive effector of the non-canonical Wnt signaling pathway, acting
CC downstream of WNT5A, MAP3K7/TAK1 and HIPK2. Negative regulator of the
CC canonical Wnt/beta-catenin signaling pathway. Binds to and
CC phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the
CC TCF7L2/LEF1/beta-catenin complex from DNA, as well as the
CC ubiquitination and subsequent proteolysis of LEF1. Together these
CC effects inhibit the transcriptional activation of canonical Wnt/beta-
CC catenin target genes. Negative regulator of the Notch signaling
CC pathway. Binds to and phosphorylates NOTCH1, thereby preventing the
CC formation of a transcriptionally active ternary complex of NOTCH1,
CC RBPJ/RBPSUH and MAML1. Negative regulator of the MYB family of
CC transcription factors. Phosphorylation of MYB leads to its subsequent
CC proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their
CC interaction with the coactivator CREBBP. Other transcription factors
CC may also be inhibited by direct phosphorylation of CREBBP itself. Acts
CC downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in
CC turn required for activation of NLK by MAP3K7/TAK1. Upon IL1B stimulus,
CC cooperates with ATF5 to activate the transactivation activity of C/EBP
CC subfamily members. Phosphorylates ATF5 but also stabilizes ATF5 protein
CC levels in a kinase-independent manner (By similarity).
CC {ECO:0000250|UniProtKB:Q9UBE8, ECO:0000269|PubMed:10391247,
CC ECO:0000269|PubMed:11745377, ECO:0000269|PubMed:12482967,
CC ECO:0000269|PubMed:12556497, ECO:0000269|PubMed:14720327,
CC ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15082531,
CC ECO:0000269|PubMed:15308626, ECO:0000269|PubMed:16055500,
CC ECO:0000269|PubMed:17785444, ECO:0000269|PubMed:18765672,
CC ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20194509,
CC ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21118996,
CC ECO:0000269|PubMed:9448268}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.24;
CC Evidence={ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:17785444};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.24; Evidence={ECO:0000269|PubMed:15004007,
CC ECO:0000269|PubMed:17785444};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Activated by the non-canonical Wnt signaling
CC pathway, in which WNT5A leads to activation of MAP3K7/TAK1 and HIPK2,
CC which subsequently phosphorylates and activates this protein. Activated
CC by dimerization and subsequent intermolecular autophosphorylation on
CC Thr-298. Other cytokines such as IL6 may also activate this regulatory
CC circuit. {ECO:0000269|PubMed:10391247, ECO:0000269|PubMed:12482967,
CC ECO:0000269|PubMed:16055500, ECO:0000269|PubMed:21118996,
CC ECO:0000269|PubMed:9448268}.
CC -!- SUBUNIT: Homodimer. Homodimerization is required for intermolecular
CC autophosphorylation, kinase activation and nuclear localization
CC (PubMed:21118996). Interacts with RNF138/NARF (By similarity).
CC Interacts with FOXO1 and FOXO3 (By similarity). Interacts with the
CC upstream activating kinases HIPK2 and MAP3K7/TAK1. Interaction with
CC MAP3K7/TAK1 seems to be indirect, and may be mediated by other proteins
CC such as STAT3, TAB1 and TAB2. Interacts with and phosphorylates a
CC number of transcription factors including FOXO4, LEF1, MYB, MYBL1,
CC MYBL2, NOTCH1 and TCF7L2/TCF4. May interact with components of cullin-
CC RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase
CC complexes. Interacts with MEF2A (PubMed:12556497, PubMed:15004007,
CC PubMed:15082531, PubMed:15308626, PubMed:16055500, PubMed:17785444,
CC PubMed:18765672, PubMed:20118921, PubMed:20194509, PubMed:20874444).
CC Interacts with ATF5; the interaction stabilizes ATF5 at the protein
CC level in a kinase-independent manner (By similarity).
CC {ECO:0000250|UniProtKB:Q9UBE8, ECO:0000269|PubMed:12556497,
CC ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15082531,
CC ECO:0000269|PubMed:15308626, ECO:0000269|PubMed:16055500,
CC ECO:0000269|PubMed:17785444, ECO:0000269|PubMed:18765672,
CC ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20194509,
CC ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21118996}.
CC -!- INTERACTION:
CC O54949; Q9QZR5: Hipk2; NbExp=2; IntAct=EBI-366894, EBI-366905;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Predominantly nuclear. A
CC smaller fraction is cytoplasmic.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in the brain, and at lower
CC levels in heart, kidney, lung and liver. {ECO:0000269|PubMed:9448268}.
CC -!- DOMAIN: Contains a TQE activation loop motif in which
CC autophosphorylation of the threonine residue (Thr-298) is sufficient
CC for kinase activation. This mode of activation contrasts with that of
CC classical MAP kinases, which contain a TXY activation loop motif in
CC which phosphorylation of both the threonine and tyrosine residues is
CC required for kinase activation.
CC -!- PTM: Phosphorylated on Thr-298. Intermolecular autophosphorylation on
CC Thr-298 activates the enzyme. {ECO:0000269|PubMed:21118996}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC24499.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF036332; AAC24499.1; ALT_INIT; mRNA.
DR EMBL; AL591177; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591376; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC057667; AAH57667.2; -; mRNA.
DR EMBL; BC058652; AAH58652.2; -; mRNA.
DR CCDS; CCDS25113.2; -.
DR RefSeq; NP_032728.3; NM_008702.3.
DR AlphaFoldDB; O54949; -.
DR SMR; O54949; -.
DR BioGRID; 201785; 1.
DR IntAct; O54949; 2.
DR STRING; 10090.ENSMUSP00000119345; -.
DR iPTMnet; O54949; -.
DR PhosphoSitePlus; O54949; -.
DR EPD; O54949; -.
DR MaxQB; O54949; -.
DR PaxDb; O54949; -.
DR PRIDE; O54949; -.
DR ProteomicsDB; 293576; -.
DR Antibodypedia; 13947; 389 antibodies from 37 providers.
DR DNASU; 18099; -.
DR Ensembl; ENSMUST00000142739; ENSMUSP00000119345; ENSMUSG00000017376.
DR GeneID; 18099; -.
DR KEGG; mmu:18099; -.
DR UCSC; uc007kjw.1; mouse.
DR CTD; 51701; -.
DR MGI; MGI:1201387; Nlk.
DR VEuPathDB; HostDB:ENSMUSG00000017376; -.
DR eggNOG; KOG0664; Eukaryota.
DR GeneTree; ENSGT00940000158363; -.
DR HOGENOM; CLU_000288_133_2_1; -.
DR InParanoid; O54949; -.
DR OMA; HSCMCRC; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; O54949; -.
DR TreeFam; TF315210; -.
DR Reactome; R-MMU-4086398; Ca2+ pathway.
DR BioGRID-ORCS; 18099; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Nlk; mouse.
DR PRO; PR:O54949; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O54949; protein.
DR Bgee; ENSMUSG00000017376; Expressed in rostral migratory stream and 255 other tissues.
DR ExpressionAtlas; O54949; baseline and differential.
DR Genevisible; O54949; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0042169; F:SH2 domain binding; IPI:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0042501; P:serine phosphorylation of STAT protein; IDA:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS01351; MAPK; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transcription; Transcription regulation;
KW Transferase; Wnt signaling pathway.
FT CHAIN 1..527
FT /note="Serine/threonine-protein kinase NLK"
FT /id="PRO_0000186337"
FT DOMAIN 138..427
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..304
FT /note="Required for interaction with TAB2"
FT /evidence="ECO:0000269|PubMed:20194509"
FT REGION 1..125
FT /note="Sufficient for interaction with DAPK3"
FT /evidence="ECO:0000250"
FT REGION 22..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 90..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 124..416
FT /note="Sufficient for interaction with DAPK3"
FT /evidence="ECO:0000250"
FT REGION 428..527
FT /note="Required for homodimerization and kinase activation
FT and localization to the nucleus"
FT REGION 434..527
FT /note="Required for interaction with TAB2"
FT /evidence="ECO:0000269|PubMed:20194509"
FT MOTIF 298..300
FT /note="TQE"
FT COMPBIAS 25..53
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 264
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 144..152
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 167
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 298
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:21118996,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 522
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBE8"
FT MUTAGEN 167
FT /note="K->M: Abrogates kinase activity and
FT autophosphorylation. Retains ability to homodimerize.
FT Abrogates ability to induce ubiquitination and degradation
FT of LEF1 and repress canonical Wnt/beta-catenin signaling.
FT Abrogates ability to induce MYB degradation, and reduces
FT ability to repress MYBL1 and MYBL2."
FT /evidence="ECO:0000269|PubMed:10391247,
FT ECO:0000269|PubMed:12556497, ECO:0000269|PubMed:15082531,
FT ECO:0000269|PubMed:16055500, ECO:0000269|PubMed:20118921,
FT ECO:0000269|PubMed:20194509, ECO:0000269|PubMed:21118996,
FT ECO:0000269|PubMed:9448268"
FT MUTAGEN 298
FT /note="T->D,E: Abrogates autophosphorylation."
FT /evidence="ECO:0000269|PubMed:15082531,
FT ECO:0000269|PubMed:21118996, ECO:0000269|PubMed:9448268"
FT MUTAGEN 298
FT /note="T->V: Abrogates autophosphorylation. Retains ability
FT to homodimerize. Abrogates ability to induce MYB
FT degradation."
FT /evidence="ECO:0000269|PubMed:15082531,
FT ECO:0000269|PubMed:21118996, ECO:0000269|PubMed:9448268"
FT MUTAGEN 437
FT /note="C->S: Retains kinase activity."
FT /evidence="ECO:0000269|PubMed:10391247,
FT ECO:0000269|PubMed:21118996"
FT MUTAGEN 437
FT /note="C->Y: Abrogates homodimerization and intermolecular
FT autophosphorylation, with consequent loss of kinase
FT activity. Loss of nuclear localization."
FT /evidence="ECO:0000269|PubMed:10391247,
FT ECO:0000269|PubMed:21118996"
FT CONFLICT 69
FT /note="S -> P (in Ref. 1; AAC24499)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 527 AA; 58313 MW; CE6D5DCCB9133989 CRC64;
MSLCGTRANA KMMAAYNGGT SAAAAGHHHH HHHHLPHLPP PHLHHHHHPQ HHLHPGSAAA
VHPVQQHTSS AAAAAAAAAA AAAMLNPGQQ QPYFPSPAPG QAPGPAAAAP AQVQAAAAAT
VKAHHHQHSH HPQQQLDIEP DRPIGYGAFG VVWSVTDPRD GKRVALKKMP NVFQNLVSCK
RVFRELKMLC FFKHDNVLSA LDILQPPHID YFEEIYVVTE LMQSDLHKII VSPQPLSSDH
VKVFLYQILR GLKYLHSAGI LHRDIKPGNL LVNSNCVLKI CDFGLARVEE LDESRHMTQE
VVTQYYRAPE ILMGSRHYSN AIDIWSVGCI FAELLGRRIL FQAQSPIQQL DLITDLLGTP
SLEAMRTACE GAKAHILRGP HKQPSLPVLY TLSSQATHEA VHLLCRMLVF DPSKRISAKD
ALAHPYLDEG RLRYHTCMCK CCFSTSTGRV YTSDFEPVTN PKFDDTFEKN LSSVRQVKEI
IHQFILEQQK GNRVPLCINP QSAAFKSFIS STVAQPSEMP PSPLVWE
