NLK

Gene Information

Official Symbol: NLK
Official Name: nemo like kinase
Aliases and Previous Symbols: N/A
Entrez ID: 51701
UniProt: Q9UBE8
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: N/A
UniProt Summary: Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination. Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2. Activation of this pathway causes binding to and phosphorylation of the histone methyltransferase SETDB1. The NLK- SETDB1 complex subsequently interacts with PPARG, leading to methylation of PPARG target promoters at histone H3K9 and transcriptional silencing. The resulting loss of PPARG target gene transcription inhibits adipogenesis and promotes osteoblastogenesis in mesenchymal stem cells (MSCs). Negative regulator of the canonical Wnt/beta-catenin signaling pathway. 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. Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes. Negative regulator of the Notch signaling pathway. Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1. Negative regulator of the MYB family of transcription factors. Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP. Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself. Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1. Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members. Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613). {ECO:0000250|UniProtKB:O54949, ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:14960582, ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15764709, ECO:0000269|PubMed:17952062, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:25512613}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
LY2090314 0.003μM R08 exp500 no dilution day6	-2.25
Aminopterin 0.005μM R07 exp335	-2.18
Bortezomib 0.05μM R00 exp7	-2.16
Taxol 0.004μM R03 exp103	-2.01
UM0130462 0.025 to 0.035μM day4 R05 exp247	-1.94
Glyphosate 1000μM R06 exp283	-1.73
VE-822 0.04μM R06 exp300	1.74
SNS-032 15μM R08 exp443	1.77
JQ1 0.8μM R08 exp435	1.78
S-trityl-L-cysteine 0.5μM R05 exp243	1.8
Temozolomide 200μM R04 exp189	1.82
All-trans-Retinoic-Acid 8μM R07 exp333	1.88
Hypoxia 5%O2 R04 exp191	1.91
Nicotinamide 2000μM R01 exp50	1.92
ETC-159 50μM R08 exp480	1.93
Colchicine 0.009μM R05 exp215	2.14
Trientine 500μM R08 exp534	2.14
Momordin-Ic 10μM R08 exp506	2.37
Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307	2.7

Global Fraction of Cell Lines Where Essential: 0/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/26
breast	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/16
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 10224
Expression level (log2 read counts): 6.11

Expression Distribution

Pkinase Tyr
Pkinase

serine phosphorylation of STAT protein
MAP kinase activity
SH2 domain binding
Wnt signaling pathway, calcium modulating pathway
peptidyl-threonine phosphorylation
peptidyl-threonine modification
transforming growth factor beta receptor signaling pathway
regulation of receptor signaling pathway via JAK-STAT
regulation of receptor signaling pathway via STAT
non-canonical Wnt signaling pathway
cellular response to transforming growth factor beta stimulus
response to transforming growth factor beta
peptidyl-serine phosphorylation
protein stabilization
protein autophosphorylation
peptidyl-serine modification
transmembrane receptor protein serine/threonine kinase signaling pathway
negative regulation of Wnt signaling pathway
magnesium ion binding
protein kinase activity
regulation of protein stability
ubiquitin protein ligase binding
transcription factor binding
cell-cell signaling by wnt
Wnt signaling pathway
regulation of Wnt signaling pathway
protein serine/threonine kinase activity
MAPK cascade
signal transduction by protein phosphorylation
cell surface receptor signaling pathway involved in cell-cell signaling
cellular response to growth factor stimulus
response to growth factor
enzyme linked receptor protein signaling pathway
peptidyl-amino acid modification
protein phosphorylation
cell-cell signaling
cellular response to endogenous stimulus
negative regulation of signal transduction
phosphorylation
negative regulation of cell communication