======= CHEK1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CHEK1
  * **<color #00a2e8>Official Name</color>**: checkpoint kinase 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1111|1111]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O14757|O14757]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CHEK1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CHEK1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/603078|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene belongs to the Ser/Thr protein kinase family. It is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. This protein acts to integrate signals from ATM and ATR, two cell cycle proteins involved in DNA damage responses, that also associate with chromatin in meiotic prophase I. Phosphorylation of CDC25A protein phosphatase by this protein is required for cells to delay cell cycle progression in response to double-strand DNA breaks. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2011]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser- 124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell- cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest.

<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'>
|histone H3-T11 phosphorylation|
|histone kinase activity (H3-T11 specific)|
|regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage|
|histone-threonine phosphorylation|
|DNA damage induced protein phosphorylation|
|regulation of mitotic centrosome separation|
|chromatin-mediated maintenance of transcription|
|signal transduction involved in G2 DNA damage checkpoint|
|replicative senescence|
|regulation of histone H3-K9 acetylation|
|G2 DNA damage checkpoint|
|condensed nuclear chromosome|
|histone phosphorylation|
|negative regulation of G0 to G1 transition|
|negative regulation of mitotic nuclear division|
|regulation of G0 to G1 transition|
|regulation of double-strand break repair via homologous recombination|
|negative regulation of nuclear division|
|chromosome, telomeric region|
|regulation of histone acetylation|
|regulation of centrosome cycle|
|regulation of peptidyl-lysine acetylation|
|positive regulation of gene expression, epigenetic|
|cell aging|
|chromatin organization involved in regulation of transcription|
|regulation of protein acetylation|
|signal transduction involved in DNA integrity checkpoint|
|signal transduction involved in DNA damage checkpoint|
|signal transduction involved in cell cycle checkpoint|
|regulation of double-strand break repair|
|cellular response to mechanical stimulus|
|kinase activity|
|peptidyl-threonine phosphorylation|
|cellular response to UV|
|peptidyl-threonine modification|
|negative regulation of cell cycle G2/M phase transition|
|signal transduction in response to DNA damage|
|regulation of DNA recombination|
|cellular response to light stimulus|
|chromatin|
|regulation of transcription from RNA polymerase II promoter in response to stress|
|regulation of DNA repair|
|regulation of DNA-templated transcription in response to stress|
|DNA damage checkpoint|
|response to UV|
|DNA integrity checkpoint|
|regulation of histone modification|
|regulation of mitotic nuclear division|
|cellular response to radiation|
|regulation of signal transduction by p53 class mediator|
|regulation of chromatin organization|
|regulation of microtubule cytoskeleton organization|
|regulation of nuclear division|
|cell cycle checkpoint|
|regulation of cell cycle G2/M phase transition|
|response to mechanical stimulus|
|DNA replication|
|regulation of response to DNA damage stimulus|
|regulation of microtubule-based process|
|negative regulation of cell cycle phase transition|
|regulation of gene expression, epigenetic|
|protein kinase activity|
|protein domain specific binding|
|aging|
|response to light stimulus|
|negative regulation of mitotic cell cycle|
|cellular response to environmental stimulus|
|cellular response to abiotic stimulus|
|negative regulation of cell cycle process|
|cellular response to external stimulus|
|regulation of chromosome organization|
|regulation of DNA metabolic process|
|protein serine/threonine kinase activity|
|histone modification|
|negative regulation of organelle organization|
|covalent chromatin modification|
|positive regulation of cell cycle|
|response to radiation|
|regulation of cell cycle phase transition|
|centrosome|
|DNA repair|
|regulation of cytoskeleton organization|
|negative regulation of cell cycle|
|protein-containing complex|
|regulation of mitotic cell cycle|
|intracellular membrane-bounded organelle|
|chromatin organization|
|negative regulation of cellular component organization|
|regulation of cellular response to stress|
|DNA metabolic process|
|regulation of cell cycle process|
|cellular response to DNA damage stimulus|
|peptidyl-amino acid modification|
|apoptotic process|
|protein phosphorylation|
|programmed cell death|
|chromosome organization|
|cell death|
|response to abiotic stimulus|
|regulation of cell cycle|
|phosphorylation|
|regulation of organelle organization|
|cell cycle|
|regulation of response to stress|
|ATP binding|
|positive regulation of transcription, DNA-templated|
|extracellular space|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|intracellular signal transduction|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|positive regulation of RNA metabolic process|
|macromolecule biosynthetic 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='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:exp212|Phenformin 20μM R05 exp212]]|-1.9|
|[[:results:exp116|AICAR 240μM R03 exp116]]|-1.87|
|[[:results:exp536|Vitamin-D3 40μM R08 exp536]]|-1.81|
|[[:results:exp293|Myriocin 25μM R06 exp293]]|-1.74|
|[[:results:exp527|Tanespimycin 14μM R08 exp527]]|-1.73|
|[[:results:exp198|Etoposide 0.1μM R05 exp198]]|1.94|
|[[:results:exp115|A-366 10μM R03 exp115]]|1.95|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:p:prim1|PRIM1]]|0.422|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 721/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|1/1|
|909776.0|1/1|
|bile duct|28/28|
|blood|28/28|
|bone|25/25|
|breast|32/33|
|central nervous system|56/56|
|cervix|4/4|
|colorectal|16/17|
|esophagus|13/13|
|fibroblast|1/1|
|gastric|15/15|
|kidney|21/21|
|liver|20/20|
|lung|75/75|
|lymphocyte|14/14|
|ovary|25/26|
|pancreas|23/24|
|peripheral nervous system|16/16|
|plasma cell|15/15|
|prostate|1/1|
|skin|24/24|
|soft tissue|6/7|
|thyroid|2/2|
|upper aerodigestive|22/22|
|urinary tract|29/29|
|uterus|5/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1469
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.74 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CHEK1 Expression in NALM6 Cells: 6.74'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>