======= CDK2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CDK2
  * **<color #00a2e8>Official Name</color>**: cyclin dependent kinase 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1017|1017]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P24941|P24941]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CDK2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CDK2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/116953|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of a family of serine/threonine protein kinases that participate in cell cycle regulation. The encoded protein is the catalytic subunit of the cyclin-dependent protein kinase complex, which regulates progression through the cell cycle. Activity of this protein is especially critical during the G1 to S phase transition. This protein associates with and regulated by other subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A), and p27Kip1 (CDKN1B). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2- mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity). Phosphorylates CDK2AP2 (PubMed:12944431). {ECO:0000250|UniProtKB:P97377, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:10884347, ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:11051553, ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:12944431, ECO:0000269|PubMed:15800615, ECO:0000269|PubMed:17495531, ECO:0000269|PubMed:18372919, ECO:0000269|PubMed:19966300, ECO:0000269|PubMed:20079829, ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:20195506, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:21319273, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:28666995}.

<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'>
|positive regulation of DNA-dependent DNA replication initiation|
|Y chromosome|
|cyclin E2-CDK2 complex|
|cyclin A1-CDK2 complex|
|cyclin E1-CDK2 complex|
|cyclin A2-CDK2 complex|
|cyclin-dependent protein kinase activity|
|X chromosome|
|histone kinase activity|
|regulation of DNA-dependent DNA replication initiation|
|positive regulation of DNA-dependent DNA replication|
|cellular response to nitric oxide|
|cellular response to reactive nitrogen species|
|response to nitric oxide|
|centriole replication|
|centriole assembly|
|condensed chromosome|
|histone phosphorylation|
|cyclin-dependent protein serine/threonine kinase activity|
|cyclin-dependent protein kinase holoenzyme complex|
|centrosome duplication|
|cyclin binding|
|positive regulation of DNA replication|
|chromosome, telomeric region|
|response to bronchodilator|
|Cajal body|
|regulation of DNA-dependent DNA replication|
|DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest|
|intracellular signal transduction involved in G1 DNA damage checkpoint|
|signal transduction involved in mitotic DNA integrity checkpoint|
|signal transduction involved in mitotic DNA damage checkpoint|
|signal transduction involved in mitotic G1 DNA damage checkpoint|
|signal transduction involved in mitotic cell cycle checkpoint|
|mitotic G1 DNA damage checkpoint|
|mitotic G1/S transition checkpoint|
|G1 DNA damage checkpoint|
|signal transduction involved in DNA damage checkpoint|
|signal transduction involved in DNA integrity checkpoint|
|signal transduction involved in cell cycle checkpoint|
|DNA damage response, signal transduction by p53 class mediator|
|positive regulation of cell cycle arrest|
|anaphase-promoting complex-dependent catabolic process|
|centrosome cycle|
|microtubule organizing center organization|
|mitotic DNA damage checkpoint|
|negative regulation of G1/S transition of mitotic cell cycle|
|signal transduction in response to DNA damage|
|mitotic DNA integrity checkpoint|
|negative regulation of cell cycle G1/S phase transition|
|regulation of cell cycle arrest|
|regulation of DNA replication|
|G1/S transition of mitotic cell cycle|
|cell cycle G1/S phase transition|
|signal transduction by p53 class mediator|
|regulation of gene silencing|
|cellular response to reactive oxygen species|
|G2/M transition of mitotic cell cycle|
|DNA damage checkpoint|
|cell cycle G2/M phase transition|
|DNA integrity checkpoint|
|regulation of G1/S transition of mitotic cell cycle|
|mitotic cell cycle checkpoint|
|regulation of cell cycle G1/S phase transition|
|potassium ion transport|
|peptidyl-serine phosphorylation|
|regulation of signal transduction by p53 class mediator|
|positive regulation of DNA metabolic process|
|cell cycle checkpoint|
|response to reactive oxygen species|
|regulation of G2/M transition of mitotic cell cycle|
|peptidyl-serine modification|
|transcription factor complex|
|regulation of cell cycle G2/M phase transition|
|negative regulation of mitotic cell cycle phase transition|
|DNA replication|
|magnesium ion binding|
|cellular response to inorganic substance|
|meiotic cell cycle|
|negative regulation of cell cycle phase transition|
|cellular response to oxidative stress|
|protein domain specific binding|
|Ras protein signal transduction|
|endosome|
|mitotic cell cycle phase transition|
|cell cycle phase transition|
|positive regulation of cell cycle process|
|negative regulation of mitotic cell cycle|
|small GTPase mediated signal transduction|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|negative regulation of cell cycle process|
|proteasomal protein catabolic process|
|regulation of DNA metabolic process|
|protein serine/threonine kinase activity|
|histone modification|
|covalent chromatin modification|
|positive regulation of cell cycle|
|response to oxidative stress|
|monovalent inorganic cation transport|
|cellular response to drug|
|regulation of mitotic cell cycle phase transition|
|regulation of cell cycle phase transition|
|microtubule cytoskeleton organization|
|centrosome|
|cell division|
|DNA repair|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|response to inorganic substance|
|modification-dependent macromolecule catabolic process|
|negative regulation of cell cycle|
|proteolysis involved in cellular protein catabolic process|
|mitotic cell cycle process|
|cellular protein catabolic process|
|regulation of mitotic cell cycle|
|metal ion transport|
|cellular response to nitrogen compound|
|microtubule-based process|
|protein catabolic process|
|mitotic cell cycle|
|chromatin organization|
|DNA metabolic process|
|regulation of cell cycle process|
|organelle assembly|
|cellular response to DNA damage stimulus|
|cation transport|
|negative regulation of transcription by RNA polymerase II|
|peptidyl-amino acid modification|
|cellular macromolecule catabolic process|
|positive regulation of cell population proliferation|
|protein phosphorylation|
|cell cycle process|
|response to drug|
|macromolecule catabolic process|
|cellular response to oxygen-containing compound|
|organonitrogen compound catabolic process|
|chromosome organization|
|response to nitrogen compound|
|cytoskeleton organization|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|proteolysis|
|phosphorylation|
|negative regulation of RNA metabolic process|
|cell cycle|
|ion transport|
|negative regulation of cellular macromolecule biosynthetic process|
|reproductive process|
|reproduction|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|ATP binding|
|negative regulation of cellular biosynthetic process|
|positive regulation of transcription, DNA-templated|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|regulation of cell population proliferation|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|intracellular signal transduction|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|macromolecule biosynthetic process|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of intracellular signal transduction|
|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:exp169|BH1 1μM R04 exp169]]|-2.99|
|[[:results:exp492|iCRT14 30μM R08 exp492]]|-2.78|
|[[:results:exp217|Mdivi-1 15μM R05 exp217]]|-2.65|
|[[:results:exp474|CR131-b 0.005μM R08 exp474]]|-2.35|
|[[:results:exp198|Etoposide 0.1μM R05 exp198]]|-2.19|
|[[:results:exp15|Cycloheximide 0.2μM R00 exp15]]|-2.18|
|[[:results:exp190|Vincristine 0.0005μM R04 exp190]]|-2.18|
|[[:results:exp103|Taxol 0.004μM R03 exp103]]|-2.04|
|[[:results:exp488|Hippuristanol 0.12μM R08 exp488]]|-2.02|
|[[:results:exp332|Adefovir 20μM R07 exp332]]|-1.97|
|[[:results:exp489|Hippuristanol 0.12μM R08 exp489 no dilution day6]]|-1.93|
|[[:results:exp226|Cerivastatin 0.15μM R05 exp226]]|-1.86|
|[[:results:exp184|Ixabepilone 0.004 to 0.005μM on day4 R04 exp184]]|-1.79|
|[[:results:exp59|UMK57 1μM R01 exp59]]|-1.73|
|[[:results:exp16|DABN 2μM R00 exp16]]|1.73|
|[[:results:exp67|BVD-523 15μM R02 exp67]]|1.74|
|[[:results:exp530|Thioridazine 5μM R08 exp530]]|1.75|
|[[:results:exp438|NN-Diethyl-meta-toluamide 500μM R08 exp438]]|1.81|
|[[:results:exp182|IU1-47 25μM R04 exp182]]|1.89|
|[[:results:exp32|Rifampicin 10μM R00 exp32]]|2.1|
|[[:results:exp529|Thimerosal 0.85μM R08 exp529]]|2.17|
|[[:results:exp501|Methotrexate 0.01μM R08 exp501]]|2.26|
|[[:results:exp78|Pterostilbene 16μM R02 exp78]]|2.32|
|[[:results:exp436|Dynasore 7μM R08 exp436]]|2.33|
|[[:results:exp434|Vemurafenib 6.6μM R08 exp434]]|2.42|
|[[:results:exp470|Chloroquine 32μM R08 exp470]]|2.47|
|[[:results:exp242|Radicicol 0.16μM R05 exp242]]|2.51|
|[[:results:exp493|IL-3 9ng/ml R08 exp493]]|2.56|
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|2.69|
|[[:results:exp175|3-Bromopyruvate 7μM R04 exp175]]|2.76|
|[[:results:exp407|Thapsigargin 0.005μM R07 exp407]]|2.84|
|[[:results:exp343|Centrinone 0.5μM R07 exp343]]|2.93|
|[[:results:exp6|Bortezomib 0.005μM R00 exp6]]|2.95|
|[[:results:exp454|Bafilomycin-A1 0.009μM R08 exp454]]|3.08|
|[[:results:exp512|Olaparib 4μM R08 exp512]]|3.15|
|[[:results:exp83|Trametinib 10μM R02 exp83]]|3.26|
|[[:results:exp335|Aminopterin 0.005μM R07 exp335]]|3.76|
|[[:results:exp485|GSK626616 14μM R08 exp485]]|3.79|
|[[:results:exp183|IU1-C 25μM R04 exp183]]|3.89|
|[[:results:exp75|MK-1775 0.32μM R02 exp75]]|5.42|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:c:cdc25a|CDC25A]]|0.433|
|[[:human genes:r:rrm1|RRM1]]|0.423|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 167/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|1/1|
|909776.0|0/1|
|bile duct|6/28|
|blood|3/28|
|bone|8/25|
|breast|10/33|
|central nervous system|26/56|
|cervix|1/4|
|colorectal|5/17|
|esophagus|1/13|
|fibroblast|0/1|
|gastric|4/15|
|kidney|1/21|
|liver|3/20|
|lung|15/75|
|lymphocyte|2/14|
|ovary|12/26|
|pancreas|4/24|
|peripheral nervous system|1/16|
|plasma cell|5/15|
|prostate|1/1|
|skin|3/24|
|soft tissue|1/7|
|thyroid|1/2|
|upper aerodigestive|0/22|
|urinary tract|7/29|
|uterus|4/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 5822
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.24 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CDK2 Expression in NALM6 Cells: 7.24'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>