Nlk
entrez
18099
canonical
uniprot
O54949
canonical
ensembl
ENSMUSG00000017376
resolver
ensp
ENSMUSP00000119345
resolver
enst
ENSMUST00000142739
resolver
genesymbol
Nlk
resolver
uniprot
Q3TV73
resolver
uniprot
Q5SYE6
resolver
uniprot
Q6PF98
resolver
uniprot_entry
NLK_MOUSE
resolver
uniprot_entry
Q3TV73_MOUSE
resolver
uniprot_sec
Q5SYE6
resolver
uniprot_sec
Q6PF98
resolver
activity_regulation
ACTIVITY REGULATION: Activated by the non-canonical Wnt signaling pathway, in which WNT5A leads to activation of MAP3K7/TAK1 and HIPK2, which subsequently phosphorylates and activates this protein. Activated by dimerization and subsequent intermolecular autophosphorylation on Thr-298. Other cytokines such as IL6 may also activate this regulatory circuit. {ECO:0000269|PubMed:10391247, ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:16055500, ECO:0000269|PubMed:21118996, ECO:0000269|PubMed:9448268}.
uniprot
proteins
amino_acid_sequence
MSLCGTRANAKMMAAYNGGTSAAAAGHHHHHHHHLPHLPPPHLHHHHHPQHHLHPGSAAAVHPVQQHTSSAAAAAAAAAAAAAMLNPGQQQPYFPSPAPGQAPGPAAAAPAQVQAAAAATVKAHHHQHSHHPQQQLDIEPDRPIGYGAFGVVWSVTDPRDGKRVALKKMPNVFQNLVSCKRVFRELKMLCFFKHDNVLSALDILQPPHIDYFEEIYVVTELMQSDLHKIIVSPQPLSSDHVKVFLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARVEELDESRHMTQEVVTQYYRAPEILMGSRHYSNAIDIWSVGCIFAELLGRRILFQAQSPIQQLDLITDLLGTPSLEAMRTACEGAKAHILRGPHKQPSLPVLYTLSSQATHEAVHLLCRMLVFDPSKRISAKDALAHPYLDEGRLRYHTCMCKCCFSTSTGRVYTSDFEPVTNPKFDDTFEKNLSSVRQVKEIIHQFILEQQKGNRVPLCINPQSAAFKSFISSTVAQPSEMPPSPLVWE
uniprot
proteins
ec_number
2.7.11.24
uniprot
proteins
function
FUNCTION: Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination (PubMed:10391247, PubMed:11745377, PubMed:12482967, PubMed:12556497, PubMed:14720327, PubMed:15004007, PubMed:17785444, PubMed:18765672, PubMed:20874444, PubMed:21118996, PubMed:9448268). Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2 (PubMed:15004007). Negative regulator of the canonical Wnt/beta-catenin signaling pathway (PubMed:20194509). Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1 (PubMed:12556497). Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes (PubMed:12556497). Negative regulator of the Notch signaling pathway (PubMed:20118921). Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1 (PubMed:20118921). Negative regulator of the MYB family of transcription factors (PubMed:16055500). Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP (PubMed:15082531, PubMed:15308626, PubMed:16055500). Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself (PubMed:15082531, PubMed:15308626, PubMed:16055500). Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1 (PubMed:15004007). Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members (By similarity). Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (By similarity). Acts as an inhibitor of the mTORC1 complex in response to osmotic stress by mediating phosphorylation of RPTOR, thereby preventing recruitment of the mTORC1 complex to lysosomes (By similarity). {ECO:0000250|UniProtKB:Q9UBE8, ECO:0000269|PubMed:10391247, ECO:0000269|PubMed:11745377, ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:12556497, ECO:0000269|PubMed:14720327, ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15082531, ECO:0000269|PubMed:15308626, ECO:0000269|PubMed:16055500, ECO:0000269|PubMed:17785444, ECO:0000269|PubMed:18765672, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20194509, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21118996, ECO:0000269|PubMed:9448268}.
uniprot
proteins
mass_dalton
58313
uniprot
proteins
mutagenesis
MUTAGEN 167; /note="K->M: Abrogates kinase activity and autophosphorylation. Retains ability to homodimerize. Abrogates ability to induce ubiquitination and degradation of LEF1 and repress canonical Wnt/beta-catenin signaling. Abrogates ability to induce MYB degradation, and reduces ability to repress MYBL1 and MYBL2."; /evidence="ECO:0000269|PubMed:10391247, ECO:0000269|PubMed:12556497, ECO:0000269|PubMed:15082531, ECO:0000269|PubMed:16055500, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20194509, ECO:0000269|PubMed:21118996, ECO:0000269|PubMed:9448268"; MUTAGEN 298; /note="T->D,E: Abrogates autophosphorylation."; /evidence="ECO:0000269|PubMed:15082531, ECO:0000269|PubMed:21118996, ECO:0000269|PubMed:9448268"; MUTAGEN 298; /note="T->V: Abrogates autophosphorylation. Retains ability to homodimerize. Abrogates ability to induce MYB degradation."; /evidence="ECO:0000269|PubMed:15082531, ECO:0000269|PubMed:21118996, ECO:0000269|PubMed:9448268"; MUTAGEN 437; /note="C->S: Retains kinase activity."; /evidence="ECO:0000269|PubMed:10391247, ECO:0000269|PubMed:21118996"; MUTAGEN 437; /note="C->Y: Abrogates homodimerization and intermolecular autophosphorylation, with consequent loss of kinase activity. Loss of nuclear localization."; /evidence="ECO:0000269|PubMed:10391247, ECO:0000269|PubMed:21118996
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on Thr-298. Intermolecular autophosphorylation on Thr-298 activates the enzyme. {ECO:0000269|PubMed:21118996}.
uniprot
proteins
protein_family
CMGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
MAP kinase subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10391247
uniprot
proteins
pubmed
11745377
uniprot
proteins
pubmed
12482967
uniprot
proteins
pubmed
12556497
uniprot
proteins
pubmed
14720327
uniprot
proteins
pubmed
15004007
uniprot
proteins
pubmed
15082531
uniprot
proteins
pubmed
15308626
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16055500
uniprot
proteins
pubmed
17114649
uniprot
proteins
pubmed
17785444
uniprot
proteins
pubmed
18765672
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20118921
uniprot
proteins
pubmed
20194509
uniprot
proteins
pubmed
20874444
uniprot
proteins
pubmed
21118996
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
9448268
uniprot
proteins
sequence_length
527
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21118996, ECO:0000269|PubMed:9448268}. Cytoplasm {ECO:0000269|PubMed:21118996}. Note=Predominantly nuclear. A smaller fraction is cytoplasmic. {ECO:0000269|PubMed:21118996}.
uniprot
proteins