Cyclin-dependent kinase 1

NameCyclin-dependent kinase 1
Synonyms
  • 2.7.11.22
  • CDC2
  • CDC28A
  • CDK1
  • CDKN1
  • Cell division control protein 2 homolog
  • Cell division protein kinase 1
  • p34 protein kinase
  • P34CDC2
Gene NameCDK1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002153|Cyclin-dependent kinase 1
MEDYTKIEKIGEGTYGVVYKGRHKTTGQVVAMKKIRLESEEEGVPSTAIREISLLKELRH
PNIVSLQDVLMQDSRLYLIFEFLSMDLKKYLDSIPPGQYMDSSLVKSYLYQILQGIVFCH
SRRVLHRDLKPQNLLIDDKGTIKLADFGLARAFGIPIRVYTHEVVTLWYRSPEVLLGSAR
YSTPVDIWSIGTIFAELATKKPLFHGDSEIDQLFRIFRALGTPNNEVWPEVESLQDYKNT
FPKWKPGSLASHVKNLDENGLDLLSKMLIYDPAKRISGKMALNHPYFNDLDNQIKKM
Number of residues297
Molecular Weight34095.14
Theoretical pI8.75
GO Classification
Functions
  • protein kinase activity
  • protein serine/threonine kinase activity
  • histone kinase activity
  • cyclin-dependent protein serine/threonine kinase activity
  • ATP binding
  • RNA polymerase II carboxy-terminal domain kinase activity
Processes
  • organelle organization
  • activation of MAPK activity
  • G1/S transition of mitotic cell cycle
  • peptidyl-threonine phosphorylation
  • DNA replication
  • centrosome cycle
  • peptidyl-serine phosphorylation
  • DNA repair
  • Golgi disassembly
  • regulation of transcription involved in G1/S transition of mitotic cell cycle
  • cell division
  • histone phosphorylation
  • regulation of embryonic development
  • microtubule cytoskeleton organization
  • anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
  • mitotic G2 DNA damage checkpoint
  • positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition
  • pronuclear fusion
  • regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
  • cell migration
  • protein localization to kinetochore
  • epithelial cell differentiation
  • mitotic nuclear division
  • regulation of Schwann cell differentiation
  • apoptotic process
  • positive regulation of protein localization to nucleus
  • negative regulation of apoptotic process
  • mitotic nuclear envelope disassembly
  • G2/M transition of mitotic cell cycle
  • mitotic cell cycle
Components
  • midbody
  • nuclear chromosome, telomeric region
  • nucleus
  • spindle microtubule
  • cytosol
  • extracellular exosome
  • nucleoplasm
  • centrosome
  • cytoplasm
  • mitochondrion
  • membrane
  • mitotic spindle
General FunctionRna polymerase ii carboxy-terminal domain kinase activity
Specific FunctionPlays 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, 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID29839
UniProtKB IDP06493
UniProtKB Entry NameCDK1_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0002152|894 bp
ATGGAAGATTATACCAAAATAGAGAAAATTGGAGAAGGTACCTATGGAGTTGTGTATAAG
GGTAGACACAAAACTACAGGTCAAGTGGTAGCCATGAAAAAAATCAGACTAGAAAGTGAA
GAGGAAGGGGTTCCTAGTACTGCAATTCGGGAAATTTCTCTATTAAAGGAACTTCGTCAT
CCAAATATAGTCAGTCTTCAGGATGTGCTTATGCAGGATTCCAGGTTATATCTCATCTTT
GAGTTTCTTTCCATGGATCTGAAGAAATACTTGGATTCTATCCCTCCTGGTCAGTACATG
GATTCTTCACTTGTTAAGAGTTATTTATACCAAATCCTACAGGGGATTGTGTTTTGTCAC
TCTAGAAGAGTTCTTCACAGAGACTTAAAACCTCAAAATCTCTTGATTGATGACAAAGGA
ACAATTAAACTGGCTGATTTTGGCCTTGCCAGAGCTTTTGGAATACCTATCAGAGTATAT
ACACATGAGGTAGTAACACTCTGGTACAGATCTCCAGAAGTATTGCTGGGGTCAGCTCGT
TACTCAACTCCAGTTGACATTTGGAGTATAGGCACCATATTTGCTGAACTAGCAACTAAG
AAACCACTTTTCCATGGGGATTCAGAAATTGATCAACTCTTCAGGATTTTCAGAGCTTTG
GGCACTCCCAATAATGAAGTGTGGCCAGAAGTGGAATCTTTACAGGACTATAAGAATACA
TTTCCCAAATGGAAACCAGGAAGCCTAGCATCCCATGTCAAAAACTTGGATGAAAATGGC
TTGGATTTGCTCTCGAAAATGTTAATCTATGATCCAGCCAAACGAATTTCTGGCAAAATG
GCACTGAATCATCCATATTTTAATGATTTGGACAATCAGATTAAGAAGATGTAG
GenBank Gene IDX05360
GeneCard IDNot Available
GenAtlas IDCDC2
HGNC IDHGNC:1722
Chromosome LocationNot Available
Locus10q21.1
References
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