CDK1 [The Human Chemical-Genetic Interaction Map Project]

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======= CDK1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CDK1
  * **<color #00a2e8>Official Name</color>**: cyclin dependent kinase 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=983|983]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P06493|P06493]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CDK1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CDK1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/116940|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G1/S and G2/M phase transitions of eukaryotic cell cycle. Mitotic cyclins stably associate with this protein and function as regulatory subunits. The kinase activity of this protein is controlled by cyclin accumulation and destruction through the cell cycle. The phosphorylation and dephosphorylation of this protein also play important regulatory roles in cell cycle control. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. Required in higher cells for entry into S-phase and mitosis. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl- xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SIRT2 and RUNX2. CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs. Essential for early stages of embryonic development. During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation. Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis. Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C- mediated dephosphorylation and restoring cell cycle progression. In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis. NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis. The phosphorylation of Bcl- xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis. In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration. CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis (PubMed:26549230). {ECO:0000269|PubMed:16371510, ECO:0000269|PubMed:16407259, ECO:0000269|PubMed:16933150, ECO:0000269|PubMed:17459720, ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:18480403, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19917720, ECO:0000269|PubMed:20171170, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:20937773, ECO:0000269|PubMed:21063390, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26549230}.

<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'>
|pronuclear fusion|
|karyogamy|
|cyclin B1-CDK1 complex|
|regulation of Schwann cell differentiation|
|cyclin-dependent protein kinase activity|
|histone kinase activity|
|positive regulation of mitochondrial ATP synthesis coupled electron transport|
|Golgi disassembly|
|regulation of mitochondrial ATP synthesis coupled electron transport|
|positive regulation of cellular respiration|
|Golgi inheritance|
|organelle inheritance|
|positive regulation of oxidative phosphorylation|
|ventricular cardiac muscle cell development|
|mitotic nuclear envelope disassembly|
|protein localization to kinetochore|
|membrane disassembly|
|ventricular cardiac muscle cell differentiation|
|nuclear envelope disassembly|
|protein localization to chromosome, centromeric region|
|mitotic G2 DNA damage checkpoint|
|RNA polymerase II CTD heptapeptide repeat kinase activity|
|positive regulation of cardiac muscle cell proliferation|
|positive regulation of G2/M transition of mitotic cell cycle|
|mitotic G2/M transition checkpoint|
|histone phosphorylation|
|cyclin-dependent protein serine/threonine kinase activity|
|G2 DNA damage checkpoint|
|regulation of oxidative phosphorylation|
|cyclin binding|
|regulation of cellular respiration|
|cyclin-dependent protein kinase holoenzyme complex|
|positive regulation of cell cycle G2/M phase transition|
|positive regulation of cardiac muscle tissue growth|
|positive regulation of DNA replication|
|positive regulation of heart growth|
|spindle microtubule|
|regulation of cardiac muscle cell proliferation|
|Hsp70 protein binding|
|chromosome condensation|
|positive regulation of cardiac muscle tissue development|
|positive regulation of ATP metabolic process|
|response to copper ion|
|response to amine|
|positive regulation of organ growth|
|response to axon injury|
|nuclear envelope organization|
|DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest|
|signal transduction involved in mitotic cell cycle checkpoint|
|signal transduction involved in mitotic DNA damage checkpoint|
|intracellular signal transduction involved in G1 DNA damage checkpoint|
|signal transduction involved in mitotic DNA integrity checkpoint|
|signal transduction involved in mitotic G1 DNA damage checkpoint|
|regulation of cardiac muscle tissue growth|
|cardiac muscle cell development|
|protein localization to chromosome|
|mitotic G1 DNA damage checkpoint|
|mitotic G1/S transition checkpoint|
|cell aging|
|response to cadmium ion|
|organelle disassembly|
|G1 DNA damage checkpoint|
|regulation of heart growth|
|cardiac cell development|
|response to activity|
|positive regulation of striated muscle tissue development|
|regulation of glial cell differentiation|
|positive regulation of muscle organ development|
|cellular response to hydrogen peroxide|
|positive regulation of muscle tissue development|
|signal transduction involved in DNA damage checkpoint|
|signal transduction involved in DNA integrity checkpoint|
|signal transduction involved in cell cycle checkpoint|
|animal organ regeneration|
|positive regulation of protein localization to nucleus|
|virus receptor activity|
|positive regulation of mitotic cell cycle phase transition|
|mitotic spindle|
|DNA damage response, signal transduction by p53 class mediator|
|regulation of cardiac muscle tissue development|
|positive regulation of cell cycle arrest|
|anaphase-promoting complex-dependent catabolic process|
|peptidyl-threonine phosphorylation|
|centrosome cycle|
|cardiac muscle cell differentiation|
|negative regulation of G2/M transition of mitotic cell cycle|
|peptidyl-threonine modification|
|microtubule organizing center organization|
|regulation of organ growth|
|positive regulation of cell cycle phase transition|
|mitotic DNA damage checkpoint|
|viral entry into host cell|
|ciliary basal body-plasma membrane docking|
|organelle fusion|
|negative regulation of cell cycle G2/M phase transition|
|negative regulation of G1/S transition of mitotic cell cycle|
|entry into host cell|
|entry into host|
|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|
|nuclear chromosome, telomeric region|
|regulation of circadian rhythm|
|cardiocyte differentiation|
|regulation of gliogenesis|
|regulation of protein localization to nucleus|
|cellular response to antibiotic|
|response to hydrogen peroxide|
|regulation of ATP metabolic process|
|signal transduction by p53 class mediator|
|response to ethanol|
|regulation of embryonic development|
|G2/M transition of mitotic cell cycle|
|cellular response to reactive oxygen species|
|DNA damage checkpoint|
|regulation of striated muscle tissue development|
|Golgi organization|
|nucleus organization|
|cell cycle G2/M phase transition|
|striated muscle cell development|
|regulation of muscle tissue development|
|regulation of muscle organ development|
|single fertilization|
|DNA integrity checkpoint|
|muscle cell development|
|regulation of G1/S transition of mitotic cell cycle|
|positive regulation of mitotic cell cycle|
|mitotic cell cycle checkpoint|
|activation of MAPK activity|
|interaction with host|
|regeneration|
|midbody|
|regulation of generation of precursor metabolites and energy|
|cardiac muscle tissue development|
|regulation of cell cycle G1/S phase transition|
|fertilization|
|organelle localization by membrane tethering|
|positive regulation of developmental growth|
|peptidyl-serine phosphorylation|
|transcription initiation from RNA polymerase II promoter|
|DNA packaging|
|membrane docking|
|cell cycle checkpoint|
|response to reactive oxygen species|
|regulation of G2/M transition of mitotic cell cycle|
|peptidyl-serine modification|
|striated muscle cell differentiation|
|viral life cycle|
|regulation of cell cycle G2/M phase transition|
|negative regulation of mitotic cell cycle phase transition|
|DNA replication|
|cellular response to toxic substance|
|DNA-templated transcription, initiation|
|negative regulation of cell cycle phase transition|
|response to alcohol|
|protein kinase activity|
|cellular response to oxidative stress|
|muscle cell differentiation|
|positive regulation of growth|
|positive regulation of MAP kinase activity|
|mitotic cell cycle phase transition|
|rhythmic process|
|aging|
|cell cycle phase transition|
|protein deubiquitination|
|striated muscle tissue development|
|positive regulation of cell cycle process|
|muscle tissue development|
|DNA conformation change|
|protein modification by small protein removal|
|response to antibiotic|
|negative regulation of mitotic cell cycle|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|positive regulation of cellular protein localization|
|negative regulation of cell cycle process|
|activation of protein kinase activity|
|regulation of developmental growth|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|cilium assembly|
|proteasomal protein catabolic process|
|protein serine/threonine kinase activity|
|histone modification|
|cilium organization|
|mitochondrial matrix|
|response to metal ion|
|covalent chromatin modification|
|positive regulation of cell cycle|
|response to oxidative stress|
|chromatin binding|
|cellular component disassembly|
|cellular response to drug|
|regulation of mitotic cell cycle phase transition|
|endomembrane system organization|
|plasma membrane bounded cell projection assembly|
|regulation of cell cycle phase transition|
|cell projection assembly|
|muscle structure development|
|microtubule cytoskeleton organization|
|transcription by RNA polymerase II|
|centrosome|
|cell division|
|response to toxic substance|
|DNA repair|
|regulation of protein serine/threonine kinase activity|
|heart development|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|response to inorganic substance|
|positive regulation of protein kinase activity|
|regulation of cellular protein localization|
|positive regulation of MAPK cascade|
|modification-dependent macromolecule catabolic process|
|cell population proliferation|
|response to wounding|
|negative regulation of cell cycle|
|positive regulation of kinase activity|
|organelle localization|
|proteolysis involved in cellular protein catabolic process|
|mitotic cell cycle process|
|cellular protein catabolic process|
|regulation of mitotic cell cycle|
|transcription, DNA-templated|
|nucleic acid-templated transcription|
|RNA biosynthetic process|
|positive regulation of transferase activity|
|regulation of growth|
|microtubule-based process|
|epithelial cell differentiation|
|protein catabolic process|
|mitotic cell cycle|
|chromatin organization|
|viral process|
|protein localization to organelle|
|DNA metabolic process|
|regulation of cell cycle process|
|regulation of MAPK cascade|
|organelle assembly|
|cellular response to DNA damage stimulus|
|symbiotic process|
|regulation of protein kinase activity|
|regulation of neurogenesis|
|interspecies interaction between organisms|
|sexual reproduction|
|membrane organization|
|circulatory system development|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|cellular macromolecule catabolic process|
|negative regulation of programmed cell death|
|regulation of cellular localization|
|positive regulation of cell population proliferation|
|response to organic cyclic compound|
|apoptotic process|
|regulation of nervous system development|
|regulation of cell development|
|endoplasmic reticulum membrane|
|cell migration|
|protein phosphorylation|
|regulation of transferase activity|
|protein modification by small protein conjugation or removal|
|negative regulation of cell death|
|multi-organism reproductive process|
|cell cycle process|
|response to organonitrogen compound|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|response to drug|
|regulation of protein localization|
|macromolecule catabolic process|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|organonitrogen compound catabolic process|
|chromosome organization|
|cell motility|
|localization of cell|
|response to nitrogen compound|
|cell death|
|nucleobase-containing compound biosynthetic process|
|cytoskeleton organization|
|epithelium development|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|cell projection organization|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|regulation of cell cycle|
|positive regulation of protein modification process|
|mitochondrion|
|proteolysis|
|phosphorylation|
|organic cyclic compound biosynthetic process|
|locomotion|
|cell cycle|
|positive regulation of developmental process|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|ATP binding|
|generation of neurons|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|cellular protein localization|
|regulation of phosphorylation|
|cellular macromolecule localization|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|neurogenesis|
|cellular nitrogen compound biosynthetic process|
|cell development|
|positive regulation of signal transduction|
|RNA metabolic process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|cellular macromolecule biosynthetic process|
|positive regulation of multicellular organismal process|
|tissue development|
|macromolecule biosynthetic process|
|organic substance catabolic 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|
|protein-containing complex subunit organization|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|membrane|
|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:exp478|Doxorubicin 0.02μM R08 exp478]]|-3.13|
|[[:results:exp80|RO-3307 4.7μM R02 exp80]]|-2.86|
|[[:results:exp468|CB-5083 0.4μM R08 exp468]]|-2.48|
|[[:results:exp99|NFN1 0.4μM R03 exp99]]|-2.11|
|[[:results:exp517|Quercetin 20μM R08 exp517]]|-2.1|
|[[:results:exp350|Deferoxamine 11μM R07 exp350]]|-2.07|
|[[:results:exp475|CyclicAMP 200μM R08 exp475]]|-2.03|
|[[:results:exp502|Milciclib 2μM R08 exp502]]|-2.01|
|[[:results:exp503|Mitomycin-C 0.06μM R08 exp503]]|-1.92|
|[[:results:exp8|Brefeldin A 0.02μM R00 exp8]]|-1.9|
|[[:results:exp162|BI-D1870 2μM R04 exp162]]|-1.85|
|[[:results:exp67|BVD-523 15μM R02 exp67]]|-1.82|
|[[:results:exp25|Oligomycin-A 2μM R00 exp25]]|-1.8|
|[[:results:exp82|Torin1 0.08μM R02 exp82]]|-1.79|
|[[:results:exp165|RO-3306 3 to 4μM on day4 R04 exp165]]|-1.76|
|[[:results:exp209|Deguelin 0.15μM R05 exp209]]|-1.73|
|[[:results:exp360|Genistein 15μM R07 exp360]]|-1.72|
|[[:results:exp293|Myriocin 25μM R06 exp293]]|-1.72|
|[[:results:exp469|CFI-400945 25μM R08 exp469]]|-1.71|
|[[:results:exp177|Apcin 25μM plus proTAME 2μM R04 exp177]]|1.7|
|[[:results:exp94|Nocodazole 0.1μM R03 exp94]]|1.74|
|[[:results:exp299|Talazoparib 0.006μM R06 exp299]]|1.75|
|[[:results:exp392|PT-1 25μM R07 exp392]]|1.8|
|[[:results:exp123|GSK-LSD1 10μM R03 exp123]]|2.04|
|[[:results:exp124|GSK343 3μM R03 exp124]]|2.05|
|[[:results:exp151|SGC0946 7μM R03 exp151]]|2.17|
</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: 733/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|1/1|
|909776.0|1/1|
|bile duct|28/28|
|blood|28/28|
|bone|26/26|
|breast|33/33|
|central nervous system|56/56|
|cervix|4/4|
|colorectal|17/17|
|esophagus|13/13|
|fibroblast|1/1|
|gastric|16/16|
|kidney|20/21|
|liver|20/20|
|lung|75/75|
|lymphocyte|16/16|
|ovary|26/26|
|pancreas|24/24|
|peripheral nervous system|16/16|
|plasma cell|15/15|
|prostate|1/1|
|skin|23/24|
|soft tissue|9/9|
|thyroid|2/2|
|upper aerodigestive|22/22|
|urinary tract|29/29|
|uterus|5/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1001
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.36 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CDK1 Expression in NALM6 Cells: 7.36'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>