NLK [The Human Chemical-Genetic Interaction Map Project]

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======= NLK =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: NLK
  * **<color #00a2e8>Official Name</color>**: nemo like kinase
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=51701|51701]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9UBE8|Q9UBE8]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=NLK&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20NLK|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/609476|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Pkinase Tyr|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|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|
|negative regulation of signaling|
|response to endogenous stimulus|
|ATP binding|
|negative regulation of response to stimulus|
|intracellular signal transduction|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

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

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:g:golga6l1|GOLGA6L1]]|0.409|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
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|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 10224
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.11 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='NLK Expression in NALM6 Cells: 6.11'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>