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Cyclin-dependent kinase 1



Rattus norvegicus (Rat)
Reviewed-Annotation score: -Experimental evidence at protein leveli


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.By similarity3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.
ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.

Enzyme regulationi

Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-161 activates it.By similarity


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei33ATPPROSITE-ProRule annotation1
Active sitei128Proton acceptorPROSITE-ProRule annotation1


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 18ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • animal organ regeneration Source: RGD
  • apoptotic process Source: UniProtKB-KW
  • cell aging Source: RGD
  • cell division Source: UniProtKB-KW
  • cell proliferation Source: RGD
  • cellular response to hydrogen peroxide Source: RGD
  • chromosome condensation Source: RGD
  • DNA repair Source: GO_Central
  • epithelial cell differentiation Source: RGD
  • Golgi disassembly Source: UniProtKB
  • microtubule cytoskeleton organization Source: GO_Central
  • mitotic cell cycle Source: RGD
  • mitotic cell cycle phase transition Source: RGD
  • mitotic G2 DNA damage checkpoint Source: RGD
  • negative regulation of apoptotic process Source: RGD
  • peptidyl-serine phosphorylation Source: UniProtKB
  • peptidyl-threonine phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of cardiac muscle cell proliferation Source: RGD
  • positive regulation of DNA replication Source: RGD
  • positive regulation of G2/M transition of mitotic cell cycle Source: RGD
  • positive regulation of gene expression Source: RGD
  • positive regulation of mitochondrial ATP synthesis coupled electron transport Source: RGD
  • positive regulation of mitotic cell cycle Source: RGD
  • positive regulation of protein import into nucleus, translocation Source: RGD
  • positive regulation of protein localization to nucleus Source: RGD
  • protein localization to kinetochore Source: RGD
  • protein phosphorylation Source: RGD
  • regulation of meiotic cell cycle Source: GO_Central
  • response to activity Source: RGD
  • response to amine Source: RGD
  • response to axon injury Source: RGD
  • response to cadmium ion Source: RGD
  • response to copper ion Source: RGD
  • response to drug Source: RGD
  • response to ethanol Source: RGD
  • response to hydrogen peroxide Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to organonitrogen compound Source: RGD
  • response to toxic substance Source: RGD
  • ventricular cardiac muscle cell development Source: RGD


Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Cell cycle, Cell division, Mitosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.22 5301
ReactomeiR-RNO-110056 MAPK3 (ERK1) activation
R-RNO-174048 APC/C:Cdc20 mediated degradation of Cyclin B
R-RNO-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-RNO-176408 Regulation of APC/C activators between G1/S and early anaphase
R-RNO-176412 Phosphorylation of the APC/C
R-RNO-176417 Phosphorylation of Emi1
R-RNO-2299718 Condensation of Prophase Chromosomes
R-RNO-2500257 Resolution of Sister Chromatid Cohesion
R-RNO-2565942 Regulation of PLK1 Activity at G2/M Transition
R-RNO-2980767 Activation of NIMA Kinases NEK9, NEK6, NEK7
R-RNO-3301854 Nuclear Pore Complex (NPC) Disassembly
R-RNO-380259 Loss of Nlp from mitotic centrosomes
R-RNO-380270 Recruitment of mitotic centrosome proteins and complexes
R-RNO-380320 Recruitment of NuMA to mitotic centrosomes
R-RNO-4419969 Depolymerisation of the Nuclear Lamina
R-RNO-5620912 Anchoring of the basal body to the plasma membrane
R-RNO-5687128 MAPK6/MAPK4 signaling
R-RNO-5689896 Ovarian tumor domain proteases
R-RNO-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-RNO-6804757 Regulation of TP53 Degradation
R-RNO-68875 Mitotic Prophase
R-RNO-69273 Cyclin A/B1/B2 associated events during G2/M transition
R-RNO-69478 G2/M DNA replication checkpoint
R-RNO-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
R-RNO-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint
R-RNO-8854518 AURKA Activation by TPX2
R-RNO-8878166 Transcriptional regulation by RUNX2

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 1 (EC:, EC:
Short name:
Alternative name(s):
Cell division control protein 2 homolog
Cell division protein kinase 1
p34 protein kinase
Gene namesi
Synonyms:Cdc2, Cdc2a, Cdkn1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi2319 Cdk1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000857271 – 297Cyclin-dependent kinase 1Add BLAST297

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei4Phosphotyrosine; by PKRBy similarity1
Modified residuei6N6-acetyllysine; alternateBy similarity1
Cross-linki6Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei9N6-acetyllysine; alternateBy similarity1
Cross-linki9Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei14Phosphothreonine; by PKMYT1By similarity1
Modified residuei15Phosphotyrosine; by PKMYT1, WEE1, WEE2 and PKC/PRKCDBy similarity1
Modified residuei15Phosphotyrosine; by WEE1 and WEE2By similarity1
Modified residuei19PhosphotyrosineBy similarity1
Cross-linki20Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei39PhosphoserineBy similarity1
Modified residuei77PhosphotyrosineBy similarity1
Cross-linki139Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei141PhosphothreonineBy similarity1
Modified residuei161Phosphothreonine; by CAKBy similarity1
Modified residuei178PhosphoserineBy similarity1
Modified residuei222PhosphothreonineBy similarity1
Modified residuei245N6-succinyllysineBy similarity1
Modified residuei248PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Thr-161 by CAK/CDK7 activates kinase activity. Phosphorylation at Thr-14 and Tyr-15 by PKMYT1 prevents nuclear translocation. Phosphorylation at Tyr-15 by WEE1 and WEE2 inhibits the protein kinase activity and acts as a negative regulator of entry into mitosis (G2 to M transition). Phosphorylation by PKMYT1 and WEE1 takes place during mitosis to keep CDK1-cyclin-B complexes inactive until the end of G2. By the end of G2, PKMYT1 and WEE1 are inactivated, but CDC25A and CDC25B are activated. Dephosphorylation by active CDC25A and CDC25B at Thr-14 and Tyr-15, leads to CDK1 activation at the G2-M transition. Phosphorylation at Tyr-15 by WEE2 during oogenesis is required to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage, a long period of quiescence at dictyate prophase I, leading to prevent meiotic reentry. Phosphorylation by WEE2 is also required for metaphase II exit during egg activation to ensure exit from meiosis in oocytes and promote pronuclear formation. Phosphorylated at Tyr-4 by PKR/EIF2AK2 upon genotoxic stress. This phosphorylation triggers CDK1 polyubiquitination and subsequent proteolysis, thus leading to G2 arrest. In response to UV irradiation, phosphorylation at Tyr-15 by PRKCD activates the G2/M DNA damage checkpoint (By similarity).By similarity
Polyubiquitinated upon genotoxic stress.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases


PTM databases




Follow a cyclic expression; during interphase, accumulates gradually following G1, S to reach a critical threshold at the end of G2, which promotes self-activation and triggers onset of mitosis. Induced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis. Expressed during S-phase in mitogen-stimulated hepatocytes.2 Publications

Gene expression databases

GenevisibleiP39951 RN


Subunit structurei

Forms a stable but non-covalent complex with a regulatory subunit and with a cyclin. Interacts with cyclins-B (CCNB1, CCNB2 and CCNB3) to form a serine/threonine kinase holoenzyme complex also known as maturation promoting factor (MPF). The cyclin subunit imparts substrate specificity to the complex. Can also form CDK1-cylin-D and CDK1-cyclin-E complexes that phosphorylate RB1 in vitro. Binds to RB1 and other transcription factors such as FOXO1 and RUNX2. Promotes G2-M transition when in complex with a cyclin-B. Interacts with DLGAP5. Binds to the CDK inhibitors CDKN1A/p21 and CDKN1B/p27. Isoform 2 is unable to complex with cyclin-B1 and also fails to bind to CDKN1A/p21. Interacts with catalytically active CCNB1 and RALBP1 during mitosis to form an endocytotic complex during interphase. Associates with cyclins-A and B1 during S-phase in regenerating hepatocytes. Interacts with FANCC. Interacts with CEP63; this interaction recruits CDK1 to centrosomes. Interacts with CENPA.By similarity2 Publications

GO - Molecular functioni

  • cyclin binding Source: RGD
  • Hsp70 protein binding Source: RGD

Protein-protein interaction databases

BioGridi248460, 1 interactor
IntActiP39951, 2 interactors


3D structure databases


Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 287Protein kinasePROSITE-ProRule annotationAdd BLAST284

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0594 Eukaryota

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE


Sequence statusi: Complete.

P39951-1 [UniParc]FASTAAdd to basket

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Mass (Da):34,135
Last modified:February 1, 1995 - v1

Sequence databases

Select the link destinations:
Links Updated
X60767 mRNA Translation: CAA43177.1
BC091549 mRNA Translation: AAH91549.1
RefSeqiNP_062169.1, NM_019296.1
XP_006256415.1, XM_006256353.3

Genome annotation databases

EnsembliENSRNOT00000000783; ENSRNOP00000000783; ENSRNOG00000000632
ENSRNOT00000081113; ENSRNOP00000070138; ENSRNOG00000000632
ENSRNOT00000086806; ENSRNOP00000072365; ENSRNOG00000000632
UCSCiRGD:2319 rat

Similar proteinsi

Entry informationi

Entry nameiCDK1_RAT
AccessioniPrimary (citable) accession number: P39951
Secondary accession number(s): Q5BJB4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: April 25, 2018
This is version 160 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program


Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health