NLK
entrez
51701
canonical
uniprot
Q9UBE8
canonical
ensembl
ENSG00000087095
resolver
ensp
ENSP00000384625
resolver
ensp
ENSP00000580870
resolver
ensp
ENSP00000625432
resolver
enst
ENST00000407008
resolver
enst
ENST00000955373
resolver
genesymbol
NLK
resolver
genesymbol_syn
LAK1
resolver
hgnc
HGNC:29858
resolver
uniprot
B2RCX1
resolver
uniprot
Q2PNI9
resolver
uniprot
Q6P2A3
resolver
uniprot_entry
NLK_HUMAN
resolver
uniprot_sec
B2RCX1
resolver
uniprot_sec
Q2PNI9
resolver
uniprot_sec
Q6P2A3
resolver
activity_regulation
ACTIVITY REGULATION: Activated by dimerization and subsequent intermolecular autophosphorylation on Thr-298 (By similarity). Activated by the non-canonical Wnt signaling pathway, in which WNT5A treatment leads to activation of MAP3K7/TAK1 and HIPK2, which subsequently phosphorylates and activates this protein. Other cytokines such as IL6 may also activate this regulatory circuit. {ECO:0000250, ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:15004007}.
uniprot
proteins
amino_acid_sequence
MSLCGARANAKMMAAYNGGTSAAAAGHHHHHHHHLPHLPPPHLHHHHHPQHHLHPGSAAAVHPVQQHTSSAAAAAAAAAAAAAMLNPGQQQPYFPSPAPGQAPGPAAAAPAQVQAAAAATVKAHHHQHSHHPQQQLDIEPDRPIGYGAFGVVWSVTDPRDGKRVALKKMPNVFQNLVSCKRVFRELKMLCFFKHDNVLSALDILQPPHIDYFEEIYVVTELMQSDLHKIIVSPQPLSSDHVKVFLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARVEELDESRHMTQEVVTQYYRAPEILMGSRHYSNAIDIWSVGCIFAELLGRRILFQAQSPIQQLDLITDLLGTPSLEAMRTACEGAKAHILRGPHKQPSLPVLYTLSSQATHEAVHLLCRMLVFDPSKRISAKDALAHPYLDEGRLRYHTCMCKCCFSTSTGRVYTSDFEPVTNPKFDDTFEKNLSSVRQVKEIIHQFILEQQKGNRVPLCINPQSAAFKSFISSTVAQPSEMPPSPLVWE
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:12482967, PubMed:14960582, PubMed:15004007, PubMed:15764709, PubMed:20061393, PubMed:20874444, PubMed:21454679). Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2 (PubMed:15004007, PubMed:15764709). Negative regulator of the canonical Wnt/beta-catenin signaling pathway (PubMed:12482967). 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:21454679). Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes (PubMed:12482967, PubMed:21454679). 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:15082531). Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP (PubMed:15082531). Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself (PubMed:15082531). Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1 (PubMed:15004007, PubMed:15764709). Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members (PubMed:25512613). Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613). 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 (PubMed:26588989). {ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:14960582, ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15082531, ECO:0000269|PubMed:15764709, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:25512613, ECO:0000269|PubMed:26588989}.
uniprot
proteins
mass_dalton
58283
uniprot
proteins
mutagenesis
MUTAGEN 167; /note="K->N: Abrogates kinase activity."; /evidence="ECO:0000269|PubMed:20061393
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on Thr-298. Intermolecular autophosphorylation on Thr-298 activates the enzyme. {ECO:0000250|UniProtKB:O54949}.
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
10863097
uniprot
proteins
pubmed
12482967
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14960582
uniprot
proteins
pubmed
15004007
uniprot
proteins
pubmed
15082531
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15764709
uniprot
proteins
pubmed
16714285
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17952062
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20061393
uniprot
proteins
pubmed
20118921
uniprot
proteins
pubmed
20874444
uniprot
proteins
pubmed
21454679
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
25358353
uniprot
proteins
pubmed
25512613
uniprot
proteins
pubmed
26588989
uniprot
proteins
sequence_length
527
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O54949}. Cytoplasm {ECO:0000250|UniProtKB:O54949}. Note=Predominantly nuclear. A smaller fraction is cytoplasmic. {ECO:0000250|UniProtKB:O54949}.
uniprot
proteins