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Protein

Cyclin-dependent kinase 1

Gene

Cdk1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Sites

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

Regions

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

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • chromatin binding Source: Ensembl
  • cyclin binding Source: RGD
  • cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
  • histone kinase activity Source: RGD
  • protein serine/threonine kinase activity Source: ParkinsonsUK-UCL
  • RNA polymerase II carboxy-terminal domain kinase activity Source: UniProtKB-EC

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: Ensembl
  • cellular response to hydrogen peroxide Source: RGD
  • chromosome condensation Source: RGD
  • epithelial cell differentiation Source: Ensembl
  • Golgi disassembly Source: UniProtKB
  • mitotic cell cycle Source: RGD
  • mitotic cell cycle phase transition Source: Ensembl
  • mitotic G2 DNA damage checkpoint Source: Ensembl
  • mitotic nuclear division Source: UniProtKB-KW
  • negative regulation of apoptotic process Source: Ensembl
  • 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 gene expression Source: RGD
  • positive regulation of mitotic cell cycle Source: RGD
  • positive regulation of protein import into nucleus, translocation Source: RGD
  • protein complex assembly Source: RGD
  • protein localization to kinetochore Source: Ensembl
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle, Cell division, Mitosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.22. 5301.
ReactomeiR-RNO-110056. MAPK3 (ERK1) activation.
R-RNO-113507. E2F-enabled inhibition of pre-replication complex formation.
R-RNO-113510. E2F mediated regulation of DNA replication.
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-6804114. TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
R-RNO-6804757. Regulation of TP53 Degradation.
R-RNO-69205. G1/S-Specific Transcription.
R-RNO-69273. Cyclin A/B1 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.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 1 (EC:2.7.11.22, EC:2.7.11.23)
Short name:
CDK1
Alternative name(s):
Cell division control protein 2 homolog
Cell division protein kinase 1
p34 protein kinase
Gene namesi
Name:Cdk1
Synonyms:Cdc2, Cdc2a, Cdkn1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi2319. Cdk1.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • cytoplasm Source: RGD
  • extracellular exosome Source: Ensembl
  • membrane Source: Ensembl
  • midbody Source: Ensembl
  • mitochondrion Source: UniProtKB-SubCell
  • mitotic spindle Source: UniProtKB
  • nuclear chromosome, telomeric region Source: Ensembl
  • nucleus Source: RGD
  • spindle microtubule Source: Ensembl
Complete GO annotation...

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-acetyllysineBy similarity1
Modified residuei9N6-acetyllysineBy similarity1
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
Modified residuei39PhosphoserineBy similarity1
Modified residuei77PhosphotyrosineBy similarity1
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

PaxDbiP39951.
PRIDEiP39951.

PTM databases

iPTMnetiP39951.
PhosphoSitePlusiP39951.

Expressioni

Inductioni

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

BgeeiENSRNOG00000000632.
GenevisibleiP39951. RN.

Interactioni

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

Protein-protein interaction databases

BioGridi248460. 1 interactor.
IntActiP39951. 2 interactors.
STRINGi10116.ENSRNOP00000000783.

Structurei

3D structure databases

ProteinModelPortaliP39951.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0594. Eukaryota.
ENOG410XPP3. LUCA.
GeneTreeiENSGT00830000128256.
HOVERGENiHBG014652.
InParanoidiP39951.
KOiK02087.
OMAiGKMALKH.
PhylomeDBiP39951.
TreeFamiTF101021.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P39951-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEDYIKIEKI GEGTYGVVYK GRHRTTGQIV AMKKIRLESE EEGVPSTAIR
60 70 80 90 100
EISLLKELRH PNIVSLQDVL MQDSRLYLIF EFLSMDLKKY LDSIPPGQFM
110 120 130 140 150
DSSLVKSYLY QILQGIVFCH SRRVLHRDLK PQNLLIDDKG TIKLADFGLA
160 170 180 190 200
RAFGIPIRVY THEVVTLWYR SPEVLLGSAR YSTPVDIWSI GTIFAELATK
210 220 230 240 250
KPLFHGDSEI DQLFRIFRAL GTPNNEVWPE VESLQDYKNT FPKWKPGSLA
260 270 280 290
SHVKNLDENG LDLLSKMLVY DPAKRISGKM ALKHPYFDDL DNQIKKM
Length:297
Mass (Da):34,135
Last modified:February 1, 1995 - v1
Checksum:i73695017E127178A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X60767 mRNA. Translation: CAA43177.1.
BC091549 mRNA. Translation: AAH91549.1.
PIRiS24913.
RefSeqiNP_062169.1. NM_019296.1.
XP_006256415.1. XM_006256353.3.
UniGeneiRn.6934.

Genome annotation databases

EnsembliENSRNOT00000000783; ENSRNOP00000000783; ENSRNOG00000000632.
ENSRNOT00000081113; ENSRNOP00000070138; ENSRNOG00000000632.
ENSRNOT00000086806; ENSRNOP00000072365; ENSRNOG00000000632.
GeneIDi54237.
KEGGirno:54237.
UCSCiRGD:2319. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X60767 mRNA. Translation: CAA43177.1.
BC091549 mRNA. Translation: AAH91549.1.
PIRiS24913.
RefSeqiNP_062169.1. NM_019296.1.
XP_006256415.1. XM_006256353.3.
UniGeneiRn.6934.

3D structure databases

ProteinModelPortaliP39951.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248460. 1 interactor.
IntActiP39951. 2 interactors.
STRINGi10116.ENSRNOP00000000783.

PTM databases

iPTMnetiP39951.
PhosphoSitePlusiP39951.

Proteomic databases

PaxDbiP39951.
PRIDEiP39951.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000000783; ENSRNOP00000000783; ENSRNOG00000000632.
ENSRNOT00000081113; ENSRNOP00000070138; ENSRNOG00000000632.
ENSRNOT00000086806; ENSRNOP00000072365; ENSRNOG00000000632.
GeneIDi54237.
KEGGirno:54237.
UCSCiRGD:2319. rat.

Organism-specific databases

CTDi983.
RGDi2319. Cdk1.

Phylogenomic databases

eggNOGiKOG0594. Eukaryota.
ENOG410XPP3. LUCA.
GeneTreeiENSGT00830000128256.
HOVERGENiHBG014652.
InParanoidiP39951.
KOiK02087.
OMAiGKMALKH.
PhylomeDBiP39951.
TreeFamiTF101021.

Enzyme and pathway databases

BRENDAi2.7.11.22. 5301.
ReactomeiR-RNO-110056. MAPK3 (ERK1) activation.
R-RNO-113507. E2F-enabled inhibition of pre-replication complex formation.
R-RNO-113510. E2F mediated regulation of DNA replication.
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-6804114. TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
R-RNO-6804757. Regulation of TP53 Degradation.
R-RNO-69205. G1/S-Specific Transcription.
R-RNO-69273. Cyclin A/B1 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.

Miscellaneous databases

PROiP39951.

Gene expression databases

BgeeiENSRNOG00000000632.
GenevisibleiP39951. RN.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCDK1_RAT
AccessioniPrimary (citable) accession number: P39951
Secondary accession number(s): Q5BJB4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: November 2, 2016
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.