CDKN1A [The Human Chemical-Genetic Interaction Map Project]

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======= CDKN1A =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CDKN1A
  * **<color #00a2e8>Official Name</color>**: cyclin dependent kinase inhibitor 1A
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1026|1026]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P38936|P38936]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CDKN1A&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CDKN1A|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/116899|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen, a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of cyclin-dependent kinase2, and may be instrumental in the execution of apoptosis following caspase activation. Mice that lack this gene have the ability to regenerate damaged or missing tissue. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Sep 2015]. 
  * **<color #00a2e8>UniProt Summary</color>**:  May be involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (PubMed:11595739). {ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:8242751, ECO:0000269|PubMed:9106657}.

<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'>
|CDI|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|cyclin-dependent protein kinase activating kinase activity|
|regulation of cardiac muscle tissue regeneration|
|negative regulation of cardiac muscle tissue regeneration|
|PCNA-p21 complex|
|intestinal epithelial cell maturation|
|columnar/cuboidal epithelial cell maturation|
|stress-induced premature senescence|
|cellular response to UV-B|
|intestinal epithelial cell development|
|cyclin-dependent protein serine/threonine kinase inhibitor activity|
|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|
|epithelial cell maturation|
|mitotic cell cycle arrest|
|response to UV-B|
|negative regulation of vascular smooth muscle cell proliferation|
|intestinal epithelial cell differentiation|
|response to hyperoxia|
|response to corticosterone|
|response to increased oxygen levels|
|protein kinase inhibitor activity|
|intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator|
|negative regulation of cyclin-dependent protein serine/threonine kinase activity|
|response to X-ray|
|negative regulation of cyclin-dependent protein kinase activity|
|cyclin binding|
|cellular response to gamma radiation|
|cyclin-dependent protein kinase holoenzyme complex|
|response to mineralocorticoid|
|cellular senescence|
|response to arsenic-containing substance|
|positive regulation of cyclin-dependent protein kinase activity|
|positive regulation of B cell proliferation|
|cellular response to amino acid starvation|
|negative regulation of smooth muscle cell proliferation|
|response to amino acid starvation|
|columnar/cuboidal epithelial cell development|
|regulation of vascular smooth muscle cell proliferation|
|intrinsic apoptotic signaling pathway by p53 class mediator|
|positive regulation of fibroblast proliferation|
|DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest|
|response to gamma radiation|
|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|
|signal transduction involved in mitotic G1 DNA damage checkpoint|
|regulation of B cell proliferation|
|mitotic G1 DNA damage checkpoint|
|mitotic G1/S transition checkpoint|
|tissue regeneration|
|cell aging|
|G1 DNA damage checkpoint|
|cellular response to ionizing radiation|
|cellular response to heat|
|intrinsic apoptotic signaling pathway in response to DNA damage|
|signal transduction involved in DNA damage checkpoint|
|signal transduction involved in DNA integrity checkpoint|
|negative regulation of wound healing|
|signal transduction involved in cell cycle checkpoint|
|animal organ regeneration|
|DNA damage response, signal transduction by p53 class mediator|
|positive regulation of cell cycle arrest|
|regulation of fibroblast proliferation|
|cellular response to UV|
|negative regulation of response to wounding|
|mitotic DNA damage checkpoint|
|positive regulation of reactive oxygen species metabolic process|
|protein import into nucleus|
|columnar/cuboidal epithelial cell differentiation|
|regulation of cyclin-dependent protein serine/threonine kinase activity|
|negative regulation of G1/S transition of mitotic cell cycle|
|regulation of cyclin-dependent protein kinase activity|
|signal transduction in response to DNA damage|
|mitotic DNA integrity checkpoint|
|negative regulation of developmental growth|
|negative regulation of cell cycle G1/S phase transition|
|regulation of cell cycle arrest|
|response to heat|
|regulation of DNA biosynthetic process|
|cellular response to light stimulus|
|import into nucleus|
|G1/S transition of mitotic cell cycle|
|cell cycle G1/S phase transition|
|signal transduction by p53 class mediator|
|positive regulation of lymphocyte proliferation|
|G2/M transition of mitotic cell cycle|
|digestive tract development|
|positive regulation of mononuclear cell proliferation|
|DNA damage checkpoint|
|negative regulation of protein serine/threonine kinase activity|
|regulation of smooth muscle cell proliferation|
|cell cycle G2/M phase transition|
|anatomical structure maturation|
|positive regulation of leukocyte proliferation|
|regulation of wound healing|
|protein import|
|digestive system development|
|response to UV|
|DNA integrity checkpoint|
|response to glucocorticoid|
|cell cycle arrest|
|intrinsic apoptotic signaling pathway|
|response to ionizing radiation|
|regulation of G1/S transition of mitotic cell cycle|
|cellular response to starvation|
|mitotic cell cycle checkpoint|
|regeneration|
|cell maturation|
|response to corticosteroid|
|protein localization to nucleus|
|regulation of cell cycle G1/S phase transition|
|positive regulation of B cell activation|
|regulation of response to wounding|
|cellular response to radiation|
|transcription initiation from RNA polymerase II promoter|
|response to temperature stimulus|
|protein stabilization|
|regulation of reactive oxygen species metabolic process|
|negative regulation of cell growth|
|epithelial cell development|
|response to ketone|
|cell cycle checkpoint|
|response to starvation|
|regulation of B cell activation|
|regulation of lymphocyte proliferation|
|regulation of mononuclear cell proliferation|
|negative regulation of mitotic cell cycle phase transition|
|DNA-templated transcription, initiation|
|regulation of leukocyte proliferation|
|negative regulation of protein kinase activity|
|negative regulation of cell cycle phase transition|
|response to alcohol|
|cellular response to nutrient levels|
|developmental maturation|
|negative regulation of growth|
|negative regulation of kinase activity|
|Ras protein signal transduction|
|nucleocytoplasmic transport|
|cellular response to extracellular stimulus|
|protein-containing complex binding|
|nuclear transport|
|mitotic cell cycle phase transition|
|negative regulation of transferase activity|
|aging|
|cell cycle phase transition|
|nuclear body|
|apoptotic signaling pathway|
|positive regulation of cell cycle process|
|regulation of protein stability|
|ubiquitin protein ligase binding|
|response to light stimulus|
|negative regulation of mitotic cell cycle|
|cellular response to environmental stimulus|
|cellular response to abiotic stimulus|
|small GTPase mediated signal transduction|
|negative regulation of cell cycle process|
|response to steroid hormone|
|regulation of developmental growth|
|cellular response to external stimulus|
|regulation of DNA metabolic process|
|positive regulation of lymphocyte activation|
|negative regulation of response to external stimulus|
|positive regulation of cell cycle|
|response to oxygen levels|
|developmental growth|
|growth|
|positive regulation of leukocyte activation|
|negative regulation of protein phosphorylation|
|regulation of mitotic cell cycle phase transition|
|regulation of cell growth|
|positive regulation of cell activation|
|establishment of protein localization to organelle|
|response to radiation|
|negative regulation of phosphorylation|
|regulation of cell cycle phase transition|
|protein kinase binding|
|wound healing|
|transcription by RNA polymerase II|
|response to nutrient levels|
|response to toxic substance|
|regulation of lymphocyte activation|
|regulation of protein serine/threonine kinase activity|
|heart development|
|response to extracellular stimulus|
|positive regulation of protein kinase activity|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|response to wounding|
|negative regulation of cell cycle|
|positive regulation of kinase activity|
|negative regulation of protein modification process|
|protein-containing complex|
|mitotic cell cycle process|
|regulation of leukocyte activation|
|regulation of mitotic cell cycle|
|regulation of cell activation|
|transcription, DNA-templated|
|nucleic acid-templated transcription|
|positive regulation of programmed cell death|
|RNA biosynthetic process|
|positive regulation of transferase activity|
|regulation of growth|
|cytokine-mediated signaling pathway|
|negative regulation of cell population proliferation|
|epithelial cell differentiation|
|mitotic cell cycle|
|positive regulation of cell death|
|perinuclear region of cytoplasm|
|protein localization to organelle|
|regulation of cell cycle process|
|cellular response to DNA damage stimulus|
|negative regulation of catalytic activity|
|regulation of protein kinase activity|
|tube development|
|response to lipid|
|nucleolus|
|circulatory system development|
|regulation of kinase activity|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|response to hormone|
|positive regulation of cell population proliferation|
|response to organic cyclic compound|
|apoptotic process|
|negative regulation of developmental process|
|regulation of transferase activity|
|intracellular protein transport|
|negative regulation of cell death|
|cell cycle process|
|response to organonitrogen compound|
|cellular response to cytokine stimulus|
|positive regulation of protein phosphorylation|
|response to drug|
|negative regulation of cellular protein metabolic process|
|programmed cell death|
|positive regulation of phosphorylation|
|response to nitrogen compound|
|cell death|
|regulation of response to external stimulus|
|nucleobase-containing compound biosynthetic process|
|response to cytokine|
|negative regulation of protein metabolic process|
|epithelium development|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|negative regulation of molecular function|
|positive regulation of immune system process|
|response to abiotic stimulus|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|regulation of cell cycle|
|positive regulation of protein modification process|
|organic cyclic compound biosynthetic process|
|cell cycle|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|regulation of response to stress|
|protein transport|
|intracellular transport|
|peptide transport|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|amide transport|
|cellular protein localization|
|regulation of phosphorylation|
|cellular macromolecule localization|
|positive regulation of cellular protein metabolic process|
|establishment of protein localization|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|cellular nitrogen compound biosynthetic process|
|cell development|
|regulation of immune system process|
|RNA metabolic process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|cellular macromolecule biosynthetic process|
|negative regulation of gene expression|
|tissue development|
|macromolecule biosynthetic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|establishment of localization in cell|
|regulation of protein modification process|
|nitrogen compound transport|
|gene expression|
</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:exp145|PNU96415E 10μM R03 exp145]]|-1.98|
|[[:results:exp240|Pyridostatin 4μM R05 exp240]]|-1.82|
|[[:results:exp198|Etoposide 0.1μM R05 exp198]]|-1.78|
|[[:results:exp512|Olaparib 4μM R08 exp512]]|-1.74|
|[[:results:exp330|5-Azacytidine 2μM R07 exp330]]|-1.73|
|[[:results:exp292|Menadione 5μM R06 exp292]]|-1.71|
|[[:results:exp505|ML-792 0.2μM R08 exp505]]|-1.7|
|[[:results:exp21|MLN-4924 0.2μM R00 exp21]]|1.87|
|[[:results:exp146|Quinacrine 2.5μM R03 exp146]]|1.87|
|[[:results:exp20|Etoposide 10μM R00 exp20]]|1.89|
|[[:results:exp508|NN-Dimethylsphingosine 2.5μM R08 exp508]]|1.9|
|[[:results:exp530|Thioridazine 5μM R08 exp530]]|1.95|
|[[:results:exp460|BML-284 0.09μM R08 exp460]]|1.98|
|[[:results:exp165|RO-3306 3 to 4μM on day4 R04 exp165]]|2|
|[[:results:exp454|Bafilomycin-A1 0.009μM R08 exp454]]|2.04|
|[[:results:exp294|Nutlin-3A 1.6μM R06 exp294]]|2.56|
|[[:results:exp2|5-Fluorouracil 20μM R00 exp2]]|3.28|
|[[:results:exp22|MLN-4924 2μM R00 exp22]]|3.42|
|[[:results:exp3|Actinomycin-D 0.001μM R00 exp3]]|4.2|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:h:hars|HARS]]|0.505|
</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>**: 16802
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.65 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CDKN1A Expression in NALM6 Cells: 6.65'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>