STK11 [The Human Chemical-Genetic Interaction Map Project]

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======= STK11 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: STK11
  * **<color #00a2e8>Official Name</color>**: serine/threonine kinase 11
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6794|6794]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q15831|Q15831]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=STK11&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20STK11|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/602216|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene, which encodes a member of the serine/threonine kinase family, regulates cell polarity and functions as a tumor suppressor. Mutations in this gene have been associated with Peutz-Jeghers syndrome, an autosomal dominant disorder characterized by the growth of polyps in the gastrointestinal tract, pigmented macules on the skin and mouth, and other neoplasms. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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). {ECO:0000269|PubMed:11430832, ECO:0000269|PubMed:12805220, ECO:0000269|PubMed:14517248, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15016379, ECO:0000269|PubMed:15733851, ECO:0000269|PubMed:15987703, ECO:0000269|PubMed:17108107, ECO:0000269|PubMed:18321849, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}.

<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|
|Pkinase Tyr|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|LRR domain binding|
|negative regulation of epithelial cell proliferation involved in prostate gland development|
|cellular response to UV-B|
|regulation of epithelial cell proliferation involved in prostate gland development|
|dendrite extension|
|positive thymic T cell selection|
|anoikis|
|Golgi localization|
|response to UV-B|
|negative regulation of TORC1 signaling|
|thymic T cell selection|
|positive T cell selection|
|protein kinase activator activity|
|positive regulation of transforming growth factor beta receptor signaling pathway|
|positive regulation of cellular response to transforming growth factor beta stimulus|
|regulation of TORC1 signaling|
|T cell selection|
|negative regulation of cold-induced thermogenesis|
|T cell differentiation in thymus|
|negative regulation of TOR signaling|
|intrinsic apoptotic signaling pathway by p53 class mediator|
|negative regulation of reproductive process|
|neuron projection extension|
|p53 binding|
|positive regulation of protein localization to nucleus|
|cellular response to UV|
|positive regulation of axonogenesis|
|developmental cell growth|
|cell growth|
|canonical Wnt signaling pathway|
|regulation of dendrite morphogenesis|
|regulation of TOR signaling|
|positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|cellular response to light stimulus|
|regulation of transforming growth factor beta receptor signaling pathway|
|developmental growth involved in morphogenesis|
|regulation of cellular response to transforming growth factor beta stimulus|
|regulation of protein localization to nucleus|
|establishment of cell polarity|
|signal transduction by p53 class mediator|
|positive regulation of autophagy|
|negative regulation of epithelial cell proliferation|
|T cell differentiation|
|response to UV|
|regulation of cold-induced thermogenesis|
|cell cycle arrest|
|intrinsic apoptotic signaling pathway|
|response to ionizing radiation|
|regulation of dendrite development|
|positive regulation of cell morphogenesis involved in differentiation|
|regulation of reproductive process|
|cellular response to radiation|
|negative regulation of canonical Wnt signaling pathway|
|T cell receptor signaling pathway|
|regulation of signal transduction by p53 class mediator|
|negative regulation of cell growth|
|regulation of axonogenesis|
|glucose homeostasis|
|carbohydrate homeostasis|
|tissue homeostasis|
|protein autophosphorylation|
|establishment or maintenance of cell polarity|
|negative regulation of Wnt signaling pathway|
|protein dephosphorylation|
|magnesium ion binding|
|regulation of protein kinase B signaling|
|regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|T cell activation|
|lymphocyte differentiation|
|negative regulation of growth|
|process utilizing autophagic mechanism|
|autophagy|
|regulation of cellular response to growth factor stimulus|
|positive regulation of neuron projection development|
|regulation of canonical Wnt signaling pathway|
|apoptotic signaling pathway|
|antigen receptor-mediated signaling pathway|
|regulation of cell morphogenesis involved in differentiation|
|response to light stimulus|
|dephosphorylation|
|cellular response to environmental stimulus|
|cellular response to abiotic stimulus|
|multicellular organismal homeostasis|
|positive regulation of cellular protein localization|
|activation of protein kinase activity|
|leukocyte differentiation|
|regulation of autophagy|
|regulation of epithelial cell proliferation|
|anatomical structure homeostasis|
|Wnt signaling pathway|
|cell-cell signaling by wnt|
|regulation of Wnt signaling pathway|
|protein serine/threonine kinase activity|
|positive regulation of cellular catabolic process|
|positive regulation of neuron differentiation|
|axonogenesis|
|positive regulation of cell projection organization|
|lymphocyte activation|
|developmental growth|
|growth|
|axon development|
|regulation of cell growth|
|cell surface receptor signaling pathway involved in cell-cell signaling|
|cell morphogenesis involved in neuron differentiation|
|positive regulation of catabolic process|
|response to radiation|
|immune response-activating cell surface receptor signaling pathway|
|positive regulation of neurogenesis|
|neuron projection morphogenesis|
|immune response-regulating cell surface receptor signaling pathway|
|plasma membrane bounded cell projection morphogenesis|
|cell projection morphogenesis|
|regulation of cell morphogenesis|
|regulation of neuron projection development|
|negative regulation of intracellular signal transduction|
|vasculature development|
|cell part morphogenesis|
|cardiovascular system development|
|positive regulation of protein kinase activity|
|positive regulation of nervous system development|
|regulation of cellular protein localization|
|positive regulation of cell development|
|spermatogenesis|
|cell morphogenesis involved in differentiation|
|hemopoiesis|
|immune response-activating signal transduction|
|male gamete generation|
|negative regulation of cell cycle|
|positive regulation of kinase activity|
|organelle localization|
|immune response-regulating signaling pathway|
|hematopoietic or lymphoid organ development|
|activation of immune response|
|immune system development|
|regulation of neuron differentiation|
|positive regulation of transferase activity|
|neuron projection development|
|regulation of growth|
|negative regulation of cell population proliferation|
|gamete generation|
|regulation of plasma membrane bounded cell projection organization|
|regulation of cell projection organization|
|cell morphogenesis|
|cellular response to DNA damage stimulus|
|regulation of protein kinase activity|
|neuron development|
|regulation of neurogenesis|
|cellular component morphogenesis|
|multicellular organismal reproductive process|
|sexual reproduction|
|regulation of cellular catabolic process|
|multicellular organism reproduction|
|positive regulation of immune response|
|circulatory system development|
|regulation of kinase activity|
|regulation of cellular localization|
|apoptotic process|
|regulation of nervous system development|
|leukocyte activation|
|regulation of cell development|
|negative regulation of developmental process|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of transferase activity|
|multi-organism reproductive process|
|regulation of catabolic process|
|cell cycle process|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|regulation of protein localization|
|programmed cell death|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|cell activation|
|cell death|
|chemical homeostasis|
|cell-cell signaling|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|regulation of immune response|
|positive regulation of immune system process|
|cell projection organization|
|response to abiotic stimulus|
|regulation of cell cycle|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|positive regulation of protein modification process|
|mitochondrion|
|negative regulation of signal transduction|
|phosphorylation|
|cell cycle|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|ATP binding|
|generation of neurons|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|neurogenesis|
|homeostatic process|
|cell development|
|positive regulation of signal transduction|
|regulation of immune system process|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|cellular catabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|membrane|
</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:exp499|LY2090314 0.003μM R08 exp499]]|-2.58|
|[[:results:exp242|Radicicol 0.16μM R05 exp242]]|-2.41|
|[[:results:exp502|Milciclib 2μM R08 exp502]]|-2.13|
|[[:results:exp216|Erlotinib 10μM R05 exp216]]|-2.03|
|[[:results:exp468|CB-5083 0.4μM R08 exp468]]|-1.96|
|[[:results:exp500|LY2090314 0.003μM R08 exp500 no dilution day6]]|-1.94|
|[[:results:exp447|Amiloride 100μM R08 exp447]]|-1.81|
|[[:results:exp211|AICAR 240μM R05 exp211]]|-1.78|
|[[:results:exp30|Rapamycin 10μM R00 exp30]]|-1.77|
|[[:results:exp248|UM0131023 0.05μM R05 exp248]]|-1.75|
|[[:results:exp227|Cryptotanshinone 12μM R05 exp227]]|-1.74|
|[[:results:exp241|QNZ 0.01μM R05 exp241]]|-1.74|
|[[:results:exp243|S-trityl-L-cysteine 0.5μM R05 exp243]]|-1.71|
|[[:results:exp459|Bleomycin 5μM R08 exp459]]|1.81|
|[[:results:exp146|Quinacrine 2.5μM R03 exp146]]|1.85|
|[[:results:exp301|VER-155008 3.9μM R06 exp301]]|2.4|
|[[:results:exp106|UM131593 0.2μM R03 exp106]]|3.91|
|[[:results:exp264|Arsenate 40μM R06 exp264]]|4.07|
|[[:results:exp389|PF-06409577 20μM R07 exp389]]|4.77|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:s:strada|STRADA]]|0.63|
|[[:human genes:p:prkab1|PRKAB1]]|0.566|
|[[:human genes:p:prkaa1|PRKAA1]]|0.537|
|[[:human genes:g:gna13|GNA13]]|0.457|
|[[:human genes:p:prkag1|PRKAG1]]|0.452|
|[[:human genes:p:prkar1a|PRKAR1A]]|0.434|
|[[:human genes:p:pten|PTEN]]|0.403|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 16/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|2/28|
|blood|1/28|
|bone|0/26|
|breast|1/33|
|central nervous system|1/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|1/16|
|kidney|2/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|1/16|
|ovary|1/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|1/15|
|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>**: 1990
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.33 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='STK11 Expression in NALM6 Cells: 6.33'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>