Cyclin-dependent kinase 1

Details

Name
Cyclin-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 Name
CDK1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002153|Cyclin-dependent kinase 1
MEDYTKIEKIGEGTYGVVYKGRHKTTGQVVAMKKIRLESEEEGVPSTAIREISLLKELRH
PNIVSLQDVLMQDSRLYLIFEFLSMDLKKYLDSIPPGQYMDSSLVKSYLYQILQGIVFCH
SRRVLHRDLKPQNLLIDDKGTIKLADFGLARAFGIPIRVYTHEVVTLWYRSPEVLLGSAR
YSTPVDIWSIGTIFAELATKKPLFHGDSEIDQLFRIFRALGTPNNEVWPEVESLQDYKNT
FPKWKPGSLASHVKNLDENGLDLLSKMLIYDPAKRISGKMALNHPYFNDLDNQIKKM
Number of residues
297
Molecular Weight
34095.14
Theoretical pI
8.75
GO Classification
Functions
ATP binding / cyclin-dependent protein serine/threonine kinase activity / histone kinase activity / protein kinase activity / protein serine/threonine kinase activity / RNA polymerase II carboxy-terminal domain kinase activity
Processes
activation of MAPK activity / anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process / apoptotic process / cell division / cell migration / centrosome cycle / DNA repair / DNA replication / epithelial cell differentiation / G1/S transition of mitotic cell cycle / G2/M transition of mitotic cell cycle / Golgi disassembly / histone phosphorylation / microtubule cytoskeleton organization / mitotic cell cycle / mitotic G2 DNA damage checkpoint / mitotic nuclear division / mitotic nuclear envelope disassembly / negative regulation of apoptotic process / organelle organization / peptidyl-serine phosphorylation / peptidyl-threonine phosphorylation / positive regulation of protein localization to nucleus / positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition / pronuclear fusion / protein localization to kinetochore / regulation of embryonic development / regulation of Schwann cell differentiation / regulation of transcription involved in G1/S transition of mitotic cell cycle / regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
Components
centrosome / cytoplasm / cytosol / extracellular exosome / membrane / midbody / mitochondrion / mitotic spindle / nuclear chromosome, telomeric region / nucleoplasm / nucleus / spindle microtubule
General Function
Rna polymerase ii carboxy-terminal domain kinase activity
Specific Function
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, 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 Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0002152|894 bp
ATGGAAGATTATACCAAAATAGAGAAAATTGGAGAAGGTACCTATGGAGTTGTGTATAAG
GGTAGACACAAAACTACAGGTCAAGTGGTAGCCATGAAAAAAATCAGACTAGAAAGTGAA
GAGGAAGGGGTTCCTAGTACTGCAATTCGGGAAATTTCTCTATTAAAGGAACTTCGTCAT
CCAAATATAGTCAGTCTTCAGGATGTGCTTATGCAGGATTCCAGGTTATATCTCATCTTT
GAGTTTCTTTCCATGGATCTGAAGAAATACTTGGATTCTATCCCTCCTGGTCAGTACATG
GATTCTTCACTTGTTAAGAGTTATTTATACCAAATCCTACAGGGGATTGTGTTTTGTCAC
TCTAGAAGAGTTCTTCACAGAGACTTAAAACCTCAAAATCTCTTGATTGATGACAAAGGA
ACAATTAAACTGGCTGATTTTGGCCTTGCCAGAGCTTTTGGAATACCTATCAGAGTATAT
ACACATGAGGTAGTAACACTCTGGTACAGATCTCCAGAAGTATTGCTGGGGTCAGCTCGT
TACTCAACTCCAGTTGACATTTGGAGTATAGGCACCATATTTGCTGAACTAGCAACTAAG
AAACCACTTTTCCATGGGGATTCAGAAATTGATCAACTCTTCAGGATTTTCAGAGCTTTG
GGCACTCCCAATAATGAAGTGTGGCCAGAAGTGGAATCTTTACAGGACTATAAGAATACA
TTTCCCAAATGGAAACCAGGAAGCCTAGCATCCCATGTCAAAAACTTGGATGAAAATGGC
TTGGATTTGCTCTCGAAAATGTTAATCTATGATCCAGCCAAACGAATTTCTGGCAAAATG
GCACTGAATCATCCATATTTTAATGATTTGGACAATCAGATTAAGAAGATGTAG
Chromosome Location
Not Available
Locus
10q21.1
External Identifiers
ResourceLink
UniProtKB IDP06493
UniProtKB Entry NameCDK1_HUMAN
GenBank Protein ID29839
GenBank Gene IDX05360
GenAtlas IDCDC2
HGNC IDHGNC:1722
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04014AlsterpaulloneexperimentalunknowninhibitorDetails
DB03496Alvocidibexperimental, investigationalunknownDetails
DB02950HymenialdisineexperimentalunknownDetails
DB02052Indirubin-3'-MonoximeexperimentalunknownbinderDetails
DB02116OlomoucineexperimentalunknownbinderDetails
DB03428SU9516experimentalunknownbinderDetails
DB08142AT-7519investigationalunknownDetails
DB06195SeliciclibinvestigationalunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails