Browse STK11

Summary
SymbolSTK11
Nameserine/threonine kinase 11
Aliases PJS; LKB1; polarization-related protein LKB1; serine/threonine kinase 11 (Peutz-Jeghers syndrome); hLKB1; li ......
Chromosomal Location19p13.3
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. Membrane Mitochondrion. Note=A small fraction localizes at membranes (By similarity). Relocates to the cytoplasm when bound to STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta). Translocates to the mitochondrion during apoptosis. Translocates to the cytoplasm in response to metformin or peroxynitrite treatment. PTEN promotes cytoplasmic localization. ; SUBCELLULAR LOCATION: Isoform 2: Nucleus Cytoplasm Note=Predominantly nuclear, but translocates to the cytoplasm in response to metformin or peroxynitrite treatment.
Domain PF00069 Protein kinase domain
Function

Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. In vein endothelial cells, inhibits PI3K/Akt signaling activity and thus induces apoptosis in response to the oxidant peroxynitrite (in vitro). Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). ; FUNCTION: Isoform 2: Has a role in spermiogenesis.

> Gene Ontology
 
Biological Process GO:0001558 regulation of cell growth
GO:0001655 urogenital system development
GO:0001894 tissue homeostasis
GO:0002429 immune response-activating cell surface receptor signaling pathway
GO:0002521 leukocyte differentiation
GO:0002757 immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0002768 immune response-regulating cell surface receptor signaling pathway
GO:0006914 autophagy
GO:0007050 cell cycle arrest
GO:0007159 leukocyte cell-cell adhesion
GO:0007163 establishment or maintenance of cell polarity
GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0007281 germ cell development
GO:0007283 spermatogenesis
GO:0007286 spermatid development
GO:0007409 axonogenesis
GO:0009314 response to radiation
GO:0009411 response to UV
GO:0009416 response to light stimulus
GO:0010212 response to ionizing radiation
GO:0010224 response to UV-B
GO:0010506 regulation of autophagy
GO:0010508 positive regulation of autophagy
GO:0010720 positive regulation of cell development
GO:0010769 regulation of cell morphogenesis involved in differentiation
GO:0010770 positive regulation of cell morphogenesis involved in differentiation
GO:0010975 regulation of neuron projection development
GO:0010976 positive regulation of neuron projection development
GO:0016049 cell growth
GO:0016055 Wnt signaling pathway
GO:0016358 dendrite development
GO:0017015 regulation of transforming growth factor beta receptor signaling pathway
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0019216 regulation of lipid metabolic process
GO:0022412 cellular process involved in reproduction in multicellular organism
GO:0022604 regulation of cell morphogenesis
GO:0030010 establishment of cell polarity
GO:0030098 lymphocyte differentiation
GO:0030111 regulation of Wnt signaling pathway
GO:0030217 T cell differentiation
GO:0030308 negative regulation of cell growth
GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway
GO:0030850 prostate gland development
GO:0031346 positive regulation of cell projection organization
GO:0031929 TOR signaling
GO:0032006 regulation of TOR signaling
GO:0032007 negative regulation of TOR signaling
GO:0032147 activation of protein kinase activity
GO:0033077 T cell differentiation in thymus
GO:0033500 carbohydrate homeostasis
GO:0033674 positive regulation of kinase activity
GO:0034504 protein localization to nucleus
GO:0034644 cellular response to UV
GO:0036399 TCR signalosome assembly
GO:0038202 TORC1 signaling
GO:0042110 T cell activation
GO:0042593 glucose homeostasis
GO:0043276 anoikis
GO:0043368 positive T cell selection
GO:0043491 protein kinase B signaling
GO:0045058 T cell selection
GO:0045059 positive thymic T cell selection
GO:0045061 thymic T cell selection
GO:0045666 positive regulation of neuron differentiation
GO:0045786 negative regulation of cell cycle
GO:0045833 negative regulation of lipid metabolic process
GO:0045860 positive regulation of protein kinase activity
GO:0045926 negative regulation of growth
GO:0046777 protein autophosphorylation
GO:0046890 regulation of lipid biosynthetic process
GO:0048232 male gamete generation
GO:0048515 spermatid differentiation
GO:0048588 developmental cell growth
GO:0048608 reproductive structure development
GO:0048667 cell morphogenesis involved in neuron differentiation
GO:0048732 gland development
GO:0048813 dendrite morphogenesis
GO:0048814 regulation of dendrite morphogenesis
GO:0048871 multicellular organismal homeostasis
GO:0050673 epithelial cell proliferation
GO:0050678 regulation of epithelial cell proliferation
GO:0050680 negative regulation of epithelial cell proliferation
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050769 positive regulation of neurogenesis
GO:0050770 regulation of axonogenesis
GO:0050772 positive regulation of axonogenesis
GO:0050773 regulation of dendrite development
GO:0050851 antigen receptor-mediated signaling pathway
GO:0050852 T cell receptor signaling pathway
GO:0051055 negative regulation of lipid biosynthetic process
GO:0051640 organelle localization
GO:0051645 Golgi localization
GO:0051896 regulation of protein kinase B signaling
GO:0051962 positive regulation of nervous system development
GO:0060070 canonical Wnt signaling pathway
GO:0060249 anatomical structure homeostasis
GO:0060560 developmental growth involved in morphogenesis
GO:0060767 epithelial cell proliferation involved in prostate gland development
GO:0060768 regulation of epithelial cell proliferation involved in prostate gland development
GO:0060770 negative regulation of epithelial cell proliferation involved in prostate gland development
GO:0061458 reproductive system development
GO:0061564 axon development
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0071214 cellular response to abiotic stimulus
GO:0071478 cellular response to radiation
GO:0071482 cellular response to light stimulus
GO:0071493 cellular response to UV-B
GO:0071559 response to transforming growth factor beta
GO:0071560 cellular response to transforming growth factor beta stimulus
GO:0071593 lymphocyte aggregation
GO:0071594 thymocyte aggregation
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0072331 signal transduction by p53 class mediator
GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator
GO:0090092 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090100 positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090287 regulation of cellular response to growth factor stimulus
GO:0097193 intrinsic apoptotic signaling pathway
GO:0097484 dendrite extension
GO:0198738 cell-cell signaling by wnt
GO:1900180 regulation of protein localization to nucleus
GO:1900182 positive regulation of protein localization to nucleus
GO:1901796 regulation of signal transduction by p53 class mediator
GO:1902532 negative regulation of intracellular signal transduction
GO:1903432 regulation of TORC1 signaling
GO:1903829 positive regulation of cellular protein localization
GO:1903844 regulation of cellular response to transforming growth factor beta stimulus
GO:1903846 positive regulation of cellular response to transforming growth factor beta stimulus
GO:1904262 negative regulation of TORC1 signaling
GO:1990138 neuron projection extension
GO:2000241 regulation of reproductive process
GO:2000242 negative regulation of reproductive process
Molecular Function GO:0000287 magnesium ion binding
GO:0002039 p53 binding
GO:0004674 protein serine/threonine kinase activity
GO:0008047 enzyme activator activity
GO:0019207 kinase regulator activity
GO:0019209 kinase activator activity
GO:0019887 protein kinase regulator activity
GO:0030275 LRR domain binding
GO:0030295 protein kinase activator activity
Cellular Component GO:0036398 TCR signalosome
> KEGG and Reactome Pathway
 
KEGG hsa04068 FoxO signaling pathway
hsa04140 Regulation of autophagy
hsa04150 mTOR signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04152 AMPK signaling pathway
hsa04530 Tight junction
hsa04920 Adipocytokine signaling pathway
Reactome R-HSA-163680: AMPK inhibits chREBP transcriptional activation activity
R-HSA-380972: Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-2428924: IGF1R signaling cascade
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-163685: Integration of energy metabolism
R-HSA-1430728: Metabolism
R-HSA-109704: PI3K Cascade
R-HSA-109703: PKB-mediated events
R-HSA-5633007: Regulation of TP53 Activity
R-HSA-6804756: Regulation of TP53 Activity through Phosphorylation
R-HSA-162582: Signal Transduction
R-HSA-74752: Signaling by Insulin receptor
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-3700989: Transcriptional Regulation by TP53
R-HSA-165159: mTOR signalling
Summary
SymbolSTK11
Nameserine/threonine kinase 11
Aliases PJS; LKB1; polarization-related protein LKB1; serine/threonine kinase 11 (Peutz-Jeghers syndrome); hLKB1; li ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between STK11 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
 
  Literatures describing the relation between STK11 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26833127Lung CarcinomaPromote immunity (infiltration)STK11/LKB1 Deficiency Promotes Neutrophil Recruitment and Proinflammatory Cytokine Production to Suppress T-cell Activity in the Lung Tumor Microenvironment.
27687306Lung adenocarcinomaPromote immunity (infiltration)Analysis of immunophenotypes revealed that LUADs with STK11 mutations exhibited relatively low levels of infiltrating CD4+/CD8+?T-cells indicative of a muted immune response.
Summary
SymbolSTK11
Nameserine/threonine kinase 11
Aliases PJS; LKB1; polarization-related protein LKB1; serine/threonine kinase 11 (Peutz-Jeghers syndrome); hLKB1; li ......
Chromosomal Location19p13.3
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 STK11 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
SymbolSTK11
Nameserine/threonine kinase 11
Aliases PJS; LKB1; polarization-related protein LKB1; serine/threonine kinase 11 (Peutz-Jeghers syndrome); hLKB1; li ......
Chromosomal Location19p13.3
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 STK11 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.3220.369
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-1.0320.633
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.2030.892
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.2310.492
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.3520.886
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.0790.98
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0440.892
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.0010.999
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0790.959
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.3190.839
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.2960.897
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0380.561
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of STK11 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141714.35.98.40.576
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1031033.3-23.30.423
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 414250250.222
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolSTK11
Nameserine/threonine kinase 11
Aliases PJS; LKB1; polarization-related protein LKB1; serine/threonine kinase 11 (Peutz-Jeghers syndrome); hLKB1; li ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of STK11. 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
SymbolSTK11
Nameserine/threonine kinase 11
Aliases PJS; LKB1; polarization-related protein LKB1; serine/threonine kinase 11 (Peutz-Jeghers syndrome); hLKB1; li ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of STK11. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by STK11.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolSTK11
Nameserine/threonine kinase 11
Aliases PJS; LKB1; polarization-related protein LKB1; serine/threonine kinase 11 (Peutz-Jeghers syndrome); hLKB1; li ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of STK11. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolSTK11
Nameserine/threonine kinase 11
Aliases PJS; LKB1; polarization-related protein LKB1; serine/threonine kinase 11 (Peutz-Jeghers syndrome); hLKB1; li ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of STK11 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolSTK11
Nameserine/threonine kinase 11
Aliases PJS; LKB1; polarization-related protein LKB1; serine/threonine kinase 11 (Peutz-Jeghers syndrome); hLKB1; li ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between STK11 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolSTK11
Nameserine/threonine kinase 11
Aliases PJS; LKB1; polarization-related protein LKB1; serine/threonine kinase 11 (Peutz-Jeghers syndrome); hLKB1; li ......
Chromosomal Location19p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting STK11 collected from DrugBank database.
> Drugs from DrugBank database
 

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