Browse NLK

Summary
SymbolNLK
Namenemo-like kinase
Aliases nemo like kinase; Protein LAK1; Serine/threonine-protein kinase NLK
Chromosomal Location17q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Nucleus Cytoplasm Note=Predominantly nuclear. A smaller fraction is cytoplasmic (By similarity).
Domain PF00069 Protein kinase domain
Function

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).

> Gene Ontology
 
Biological Process GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007223 Wnt signaling pathway, calcium modulating pathway
GO:0016055 Wnt signaling pathway
GO:0018105 peptidyl-serine phosphorylation
GO:0018107 peptidyl-threonine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0018210 peptidyl-threonine modification
GO:0030111 regulation of Wnt signaling pathway
GO:0030178 negative regulation of Wnt signaling pathway
GO:0031647 regulation of protein stability
GO:0033136 serine phosphorylation of STAT3 protein
GO:0035567 non-canonical Wnt signaling pathway
GO:0042501 serine phosphorylation of STAT protein
GO:0046425 regulation of JAK-STAT cascade
GO:0046777 protein autophosphorylation
GO:0050821 protein stabilization
GO:0071559 response to transforming growth factor beta
GO:0071560 cellular response to transforming growth factor beta stimulus
GO:0198738 cell-cell signaling by wnt
GO:1904892 regulation of STAT cascade
Molecular Function GO:0000287 magnesium ion binding
GO:0004674 protein serine/threonine kinase activity
GO:0004702 receptor signaling protein serine/threonine kinase activity
GO:0004707 MAP kinase activity
GO:0005057 receptor signaling protein activity
GO:0008134 transcription factor binding
GO:0031625 ubiquitin protein ligase binding
GO:0042169 SH2 domain binding
GO:0044389 ubiquitin-like protein ligase binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04010 MAPK signaling pathway
hsa04068 FoxO signaling pathway
hsa04310 Wnt signaling pathway
hsa04520 Adherens junction
Reactome R-HSA-3858494: Beta-catenin independent WNT signaling
R-HSA-4086398: Ca2+ pathway
R-HSA-162582: Signal Transduction
R-HSA-195721: Signaling by Wnt
Summary
SymbolNLK
Namenemo-like kinase
Aliases nemo like kinase; Protein LAK1; Serine/threonine-protein kinase NLK
Chromosomal Location17q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between NLK and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.
Summary
SymbolNLK
Namenemo-like kinase
Aliases nemo like kinase; Protein LAK1; Serine/threonine-protein kinase NLK
Chromosomal Location17q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of NLK in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen Total # shRNA with >= 4-fold: 1 Resistant to T-cell proliferation
24476824shRNAmelanomaB16Secondary screen Total # shRNA with >= 4-fold: 2 Resistant to T-cell proliferation
Summary
SymbolNLK
Namenemo-like kinase
Aliases nemo like kinase; Protein LAK1; Serine/threonine-protein kinase NLK
Chromosomal Location17q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of NLK in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.3610.156
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.8670.558
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0120.992
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0560.824
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.1890.908
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.3630.856
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0290.926
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.3090.83
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.2720.864
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.2720.823
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.5470.754
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.1710.0175
> Mutation difference between responders and non-responders
 

There is no record.
Summary
SymbolNLK
Namenemo-like kinase
Aliases nemo like kinase; Protein LAK1; Serine/threonine-protein kinase NLK
Chromosomal Location17q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NLK. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolNLK
Namenemo-like kinase
Aliases nemo like kinase; Protein LAK1; Serine/threonine-protein kinase NLK
Chromosomal Location17q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NLK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NLK.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolNLK
Namenemo-like kinase
Aliases nemo like kinase; Protein LAK1; Serine/threonine-protein kinase NLK
Chromosomal Location17q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NLK. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolNLK
Namenemo-like kinase
Aliases nemo like kinase; Protein LAK1; Serine/threonine-protein kinase NLK
Chromosomal Location17q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of NLK expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolNLK
Namenemo-like kinase
Aliases nemo like kinase; Protein LAK1; Serine/threonine-protein kinase NLK
Chromosomal Location17q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between NLK and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolNLK
Namenemo-like kinase
Aliases nemo like kinase; Protein LAK1; Serine/threonine-protein kinase NLK
Chromosomal Location17q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting NLK collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.