CDK1
Entrez ID: 983
Full name: cyclin dependent kinase 1
External links: HGNC UniprotKB Ensembl RefSeq COSMIC
Family: CMGC: CDK: CDC1
Chromosomal location: 10q21.2
Substructure location: Gatekeeper: 80 A-loop: 145...168 G-loop: 10...19 αC-helix: 40...42
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CDK1
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 mito...
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, TPPP, 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, SAMHD1, 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). Regulates the amplitude of the cyclic expression of the core clock gene ARNTL/BMAL1 by phosphorylating its transcriptional repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)-mediated ubiquitination and proteasomal degradation of NR1D1 (PubMed:27238018).
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GO - Biological processes (BP):
activation of MAPK activity, anaphase-promoting complex-dependent catabolic process, animal organ regeneration, apoptotic process, cell aging, cell division, cell migration, cell population proliferation, cellular response to hydrogen peroxide, centrosome cycle, chromosome condensation, ciliary basa...
activation of MAPK activity, anaphase-promoting complex-dependent catabolic process, animal organ regeneration, apoptotic process, cell aging, cell division, cell migration, cell population proliferation, cellular response to hydrogen peroxide, centrosome cycle, chromosome condensation, ciliary basal body-plasma membrane docking, DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest, DNA repair, DNA replication, epithelial cell differentiation, G2/M transition of mitotic cell cycle, Golgi disassembly, microtubule cytoskeleton organization, mitotic G2 DNA damage checkpoint, mitotic nuclear envelope disassembly, negative regulation of apoptotic process, peptidyl-serine phosphorylation, peptidyl-threonine phosphorylation, positive regulation of cardiac muscle cell proliferation, positive regulation of DNA replication, positive regulation of G2/M transition of mitotic cell cycle, positive regulation of gene expression, positive regulation of mitochondrial ATP synthesis coupled electron transport, positive regulation of protein import into nucleus, positive regulation of protein localization to nucleus, pronuclear fusion, protein-containing complex assembly, protein deubiquitination, protein localization to kinetochore, protein phosphorylation, regulation of circadian rhythm, regulation of embryonic development, regulation of G2/M transition of mitotic cell cycle, regulation of mitotic cell cycle phase transition, regulation of Schwann cell differentiation, response to activity, response to amine, response to axon injury, response to cadmium ion, response to copper ion, response to ethanol, response to organic cyclic compound, rhythmic process, transcription initiation from RNA polymerase II promoter, ventricular cardiac muscle cell development
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GO - Molecular function (MF):
ATP binding, chromatin binding, cyclin binding, cyclin-dependent protein kinase activity, cyclin-dependent protein serine/threonine kinase activity, histone kinase activity, Hsp70 protein binding, protein kinase activity, protein serine/threonine kinase activity, RNA polymerase II CTD heptapeptide r...
ATP binding, chromatin binding, cyclin binding, cyclin-dependent protein kinase activity, cyclin-dependent protein serine/threonine kinase activity, histone kinase activity, Hsp70 protein binding, protein kinase activity, protein serine/threonine kinase activity, RNA polymerase II CTD heptapeptide repeat kinase activity, virus receptor activity
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GO - Cellular component (CC):
centrosome, mitotic spindle, spindle microtubule, cytosol, endoplasmic reticulum membrane, extracellular exosome, mitochondrial matrix, mitochondrion, nuclear chromosome, telomeric region, nucleoplasm, nucleus, cyclin B1-CDK1 complex, cyclin-dependent protein kinase holoenzyme complex, cytoplasm, me...
centrosome, mitotic spindle, spindle microtubule, cytosol, endoplasmic reticulum membrane, extracellular exosome, mitochondrial matrix, mitochondrion, nuclear chromosome, telomeric region, nucleoplasm, nucleus, cyclin B1-CDK1 complex, cyclin-dependent protein kinase holoenzyme complex, cytoplasm, membrane, midbody
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cyclin dependent kinase 1
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*NOTE: the Kaplan plots were collected from OncoLnc