CHEK2 [The Human Chemical-Genetic Interaction Map Project]

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======= CHEK2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CHEK2
  * **<color #00a2e8>Official Name</color>**: checkpoint kinase 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=11200|11200]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O96017|O96017]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CHEK2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CHEK2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/604373|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]. 
  * **<color #00a2e8>UniProt Summary</color>**: N/A

<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|
|FHA|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|signal transduction involved in intra-S DNA damage checkpoint|
|response to bisphenol A|
|cellular response to bisphenol A|
|negative regulation of mitotic cell cycle DNA replication|
|response to glycoside|
|regulation of mitotic cell cycle DNA replication|
|negative regulation of nuclear cell cycle DNA replication|
|replicative cell aging|
|negative regulation of DNA damage checkpoint|
|negative regulation of cell cycle checkpoint|
|positive regulation of anoikis|
|DNA damage induced protein phosphorylation|
|replicative senescence|
|DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator|
|DNA damage response, signal transduction resulting in transcription|
|intra-S DNA damage checkpoint|
|regulation of DNA damage checkpoint|
|regulation of nuclear cell cycle DNA replication|
|negative regulation of cell cycle arrest|
|regulation of anoikis|
|negative regulation of DNA-dependent DNA replication|
|intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator|
|cellular response to gamma radiation|
|regulation of cell cycle checkpoint|
|mitotic spindle assembly|
|negative regulation of DNA replication|
|chromosome, telomeric region|
|intrinsic apoptotic signaling pathway by p53 class mediator|
|regulation of DNA-dependent DNA replication|
|DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest|
|response to gamma radiation|
|signal transduction involved in mitotic G1 DNA damage checkpoint|
|signal transduction involved in mitotic cell cycle checkpoint|
|signal transduction involved in mitotic DNA damage checkpoint|
|signal transduction involved in mitotic DNA integrity checkpoint|
|intracellular signal transduction involved in G1 DNA damage checkpoint|
|mitotic G1/S transition checkpoint|
|mitotic G1 DNA damage checkpoint|
|G1 DNA damage checkpoint|
|cell aging|
|cellular response to ionizing radiation|
|intrinsic apoptotic signaling pathway in response to DNA damage|
|signal transduction involved in DNA integrity checkpoint|
|signal transduction involved in DNA damage checkpoint|
|signal transduction involved in cell cycle checkpoint|
|mitotic spindle organization|
|DNA damage response, signal transduction by p53 class mediator|
|kinase activity|
|positive regulation of cell cycle arrest|
|negative regulation of response to DNA damage stimulus|
|mitotic DNA damage checkpoint|
|PML body|
|spindle assembly|
|negative regulation of G1/S transition of mitotic cell cycle|
|microtubule cytoskeleton organization involved in mitosis|
|mitotic DNA integrity checkpoint|
|signal transduction in response to DNA damage|
|negative regulation of cell cycle G1/S phase transition|
|regulation of cell cycle arrest|
|regulation of DNA replication|
|signal transduction by p53 class mediator|
|G2/M transition of mitotic cell cycle|
|DNA damage checkpoint|
|cell cycle G2/M phase transition|
|DNA integrity checkpoint|
|mitotic nuclear division|
|intrinsic apoptotic signaling pathway|
|response to ionizing radiation|
|regulation of G1/S transition of mitotic cell cycle|
|mitotic cell cycle checkpoint|
|spindle organization|
|regulation of cell cycle G1/S phase transition|
|cellular response to radiation|
|peptidyl-serine phosphorylation|
|protein stabilization|
|double-strand break repair|
|regulation of signal transduction by p53 class mediator|
|cellular response to xenobiotic stimulus|
|cell cycle checkpoint|
|protein autophosphorylation|
|peptidyl-serine modification|
|negative regulation of mitotic cell cycle phase transition|
|regulation of response to DNA damage stimulus|
|negative regulation of cell cycle phase transition|
|mitotic cell cycle phase transition|
|aging|
|cell cycle phase transition|
|apoptotic signaling pathway|
|nuclear division|
|positive regulation of cell cycle process|
|regulation of protein stability|
|ubiquitin protein ligase binding|
|response to xenobiotic stimulus|
|negative regulation of mitotic cell cycle|
|organelle fission|
|cellular response to environmental stimulus|
|cellular response to abiotic stimulus|
|negative regulation of cell cycle process|
|protein serine/threonine kinase activity|
|positive regulation of cell cycle|
|regulation of protein catabolic process|
|cellular response to drug|
|regulation of mitotic cell cycle phase transition|
|response to radiation|
|regulation of cell cycle phase transition|
|protein kinase binding|
|microtubule cytoskeleton organization|
|cell division|
|DNA repair|
|cellular response to organic cyclic compound|
|negative regulation of cell cycle|
|mitotic cell cycle process|
|cellular response to hormone stimulus|
|cellular protein catabolic process|
|regulation of mitotic cell cycle|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|microtubule-based process|
|protein catabolic process|
|mitotic cell cycle|
|positive regulation of cell death|
|regulation of cellular response to stress|
|DNA metabolic process|
|regulation of cell cycle process|
|organelle assembly|
|cellular response to DNA damage stimulus|
|protein homodimerization activity|
|peptidyl-amino acid modification|
|cellular macromolecule catabolic process|
|response to hormone|
|response to organic cyclic compound|
|apoptotic process|
|protein phosphorylation|
|Golgi apparatus|
|regulation of catabolic process|
|cell cycle process|
|positive regulation of protein phosphorylation|
|response to drug|
|macromolecule catabolic process|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|organonitrogen compound catabolic process|
|identical protein binding|
|cell death|
|cytoskeleton organization|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|response to abiotic stimulus|
|regulation of cell cycle|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|phosphorylation|
|cell cycle|
|negative regulation of cellular macromolecule biosynthetic process|
|regulation of protein phosphorylation|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|regulation of response to stress|
|ATP binding|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|positive regulation of transcription, DNA-templated|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|negative regulation of response to stimulus|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of RNA metabolic process|
|organic substance catabolic process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|cellular catabolic process|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' 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:exp121|Golgicide-A 2μM R03 exp121]]|-1.94|
|[[:results:exp240|Pyridostatin 4μM R05 exp240]]|1.7|
|[[:results:exp270|Campthothecin 0.001μM R06 exp270]]|1.77|
|[[:results:exp473|Cincreasin 100μM R08 exp473]]|1.8|
|[[:results:exp102|Nifuroxazide 5μM R03 exp102]]|1.81|
|[[:results:exp263|Aphidicolin 0.04μM R06 exp263]]|1.85|
|[[:results:exp420|Tunicamycin 0.04 to 0.125μM  on day4 R07 exp420]]|1.85|
|[[:results:exp406|Thalidomide 20μM R07 exp406]]|1.87|
|[[:results:exp52|Ribavirin 10μM R01 exp52]]|1.93|
|[[:results:exp283|Glyphosate 1000μM R06 exp283]]|1.97|
|[[:results:exp354|Diepoxybutane 3μM R07 exp354]]|2.01|
|[[:results:exp218|A-395 10μM R05 exp218]]|2.08|
|[[:results:exp343|Centrinone 0.5μM R07 exp343]]|2.1|
|[[:results:exp274|Citral 50μM R06 exp274]]|2.2|
|[[:results:exp294|Nutlin-3A 1.6μM R06 exp294]]|6.17|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</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>**: 14254
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.3 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CHEK2 Expression in NALM6 Cells: 5.3'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>