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P39951 (CDK1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-dependent kinase 1

Short name=CDK1
EC=2.7.11.22
EC=2.7.11.23
Alternative name(s):
Cell division control protein 2 homolog
Cell division protein kinase 1
p34 protein kinase
Gene names
Name:Cdk1
Synonyms:Cdc2, Cdc2a, Cdkn1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length297 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 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 By similarity. CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration. Ref.4 Ref.5 Ref.6

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

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

Enzyme regulation

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

Subunit structure

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 2is 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 By similarity. Associates with cyclins-A and B1 during S-phase in regenerating hepatocytes. Interacts with FANCC By similarity. Interacts with CEP63; this interaction recruits CDK1 to centrosomes By similarity. Ref.4 Ref.6

Subcellular location

Nucleus. Cytoplasm By similarity. Mitochondrion By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Note: Cytoplasmic during the interphase. Reversibly translocated from cytoplasm to nucleus when phosphorylated before G2-M transition when associated with cyclin B1. Accumulates in mitochondria in G2-arrested cells upon DNA- damage By similarity. Ref.3 Ref.6

Induction

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. Ref.4 Ref.6

Post-translational modification

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.

Polyubiquitinated upon genotoxic stress By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
Cell division
Mitosis
   Cellular componentCytoplasm
Cytoskeleton
Mitochondrion
Nucleus
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell aging

Inferred from direct assay PubMed 15695611. Source: RGD

cellular response to hydrogen peroxide

Inferred from expression pattern PubMed 16179908. Source: RGD

chromosome condensation

Inferred from mutant phenotype PubMed 15695611. Source: RGD

histone phosphorylation

Inferred from direct assay Ref.6. Source: GOC

mitosis

Inferred from electronic annotation. Source: UniProtKB-KW

mitotic G2 DNA damage checkpoint

Inferred from electronic annotation. Source: Ensembl

mitotic cell cycle

Inferred from expression pattern Ref.6. Source: RGD

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

organ regeneration

Inferred from mutant phenotype PubMed 15696186. Source: RGD

positive regulation of DNA replication

Inferred from mutant phenotype Ref.6. Source: RGD

positive regulation of cardiac muscle cell proliferation

Inferred from mutant phenotype PubMed 15253691. Source: RGD

positive regulation of gene expression

Inferred from mutant phenotype PubMed 18356527. Source: RGD

positive regulation of mitotic cell cycle

Inferred from mutant phenotype PubMed 15696186. Source: RGD

positive regulation of protein import into nucleus, translocation

Inferred from mutant phenotype PubMed 18356527. Source: RGD

protein complex assembly

Inferred from direct assay PubMed 19136513. Source: RGD

protein localization to kinetochore

Inferred from electronic annotation. Source: Ensembl

response to activity

Inferred from expression pattern PubMed 16826023. Source: RGD

response to amine

Inferred from expression pattern PubMed 16155410. Source: RGD

response to axon injury

Inferred from expression pattern Ref.5. Source: RGD

response to cadmium ion

Inferred from expression pattern PubMed 16730872. Source: RGD

response to copper ion

Inferred from expression pattern PubMed 19497425. Source: RGD

response to drug

Inferred from expression pattern PubMed 16427046. Source: RGD

response to ethanol

Inferred from direct assay PubMed 18181150. Source: RGD

response to hydrogen peroxide

Inferred from expression pattern PubMed 16963227. Source: RGD

response to organic cyclic compound

Inferred from expression pattern PubMed 16427046. Source: RGD

response to organonitrogen compound

Inferred from direct assay PubMed 15696186. Source: RGD

response to toxic substance

Inferred from expression pattern PubMed 19237604. Source: RGD

ventricular cardiac muscle cell development

Inferred from expression pattern PubMed 15253691. Source: RGD

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 19298605. Source: RGD

microtubule organizing center

Inferred from electronic annotation. Source: UniProtKB-SubCell

midbody

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay PubMed 15696186. Source: RGD

spindle microtubule

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA polymerase II carboxy-terminal domain kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

cyclin binding

Inferred from physical interaction PubMed 15696186. Source: RGD

cyclin-dependent protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

histone kinase activity

Inferred from direct assay Ref.6. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 297297Cyclin-dependent kinase 1
PRO_0000085727

Regions

Domain4 – 287284Protein kinase
Nucleotide binding10 – 189ATP By similarity

Sites

Active site1281Proton acceptor By similarity
Binding site331ATP By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue41Phosphotyrosine; by PKR By similarity
Modified residue61N6-acetyllysine By similarity
Modified residue91N6-acetyllysine By similarity
Modified residue141Phosphothreonine; by PKMYT1 By similarity
Modified residue151Phosphotyrosine; by PKMYT1, WEE1, WEE2 and PKC/PRKCD; alternate By similarity
Modified residue151Phosphotyrosine; by WEE1 and WEE2; alternate By similarity
Modified residue191Phosphotyrosine By similarity
Modified residue391Phosphoserine By similarity
Modified residue771Phosphotyrosine By similarity
Modified residue1611Phosphothreonine; by CAK By similarity
Modified residue1781Phosphoserine By similarity
Modified residue2221Phosphothreonine By similarity
Modified residue2451N6-succinyllysine By similarity
Modified residue2481Phosphoserine By similarity
Cross-link89Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Sequences

Sequence LengthMass (Da)Tools
P39951 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 73695017E127178A

FASTA29734,135
        10         20         30         40         50         60 
MEDYIKIEKI GEGTYGVVYK GRHRTTGQIV AMKKIRLESE EEGVPSTAIR EISLLKELRH 

        70         80         90        100        110        120 
PNIVSLQDVL MQDSRLYLIF EFLSMDLKKY LDSIPPGQFM DSSLVKSYLY QILQGIVFCH 

       130        140        150        160        170        180 
SRRVLHRDLK PQNLLIDDKG TIKLADFGLA RAFGIPIRVY THEVVTLWYR SPEVLLGSAR 

       190        200        210        220        230        240 
YSTPVDIWSI GTIFAELATK KPLFHGDSEI DQLFRIFRAL GTPNNEVWPE VESLQDYKNT 

       250        260        270        280        290 
FPKWKPGSLA SHVKNLDENG LDLLSKMLVY DPAKRISGKM ALKHPYFDDL DNQIKKM 

« Hide

References

« Hide 'large scale' references
[1]Kanaoka Y., Nojima H., Okayama H.
Submitted (JUL-1991) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Thymus.
[3]"The cdc2 kinase is a nuclear protein that is essential for mitosis in mammalian cells."
Riabowol K., Draetta G., Brizuela L., Vandre D., Beach D.
Cell 57:393-401(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[4]"Cdc2 and Cdk2 kinase activated by transforming growth factor-beta1 trigger apoptosis through the phosphorylation of retinoblastoma protein in FaO hepatoma cells."
Choi K.S., Eom Y.W., Kang Y., Ha M.J., Rhee H., Yoon J.-W., Kim S.-J.
J. Biol. Chem. 274:31775-31783(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS RB1 KINASE, INDUCTION BY TGFB1, INTERACTION WITH RB1.
[5]"Cdc2-mediated Schwann cell migration during peripheral nerve regeneration."
Han I.S., Seo T.B., Kim K.-H., Yoon J.-H., Yoon S.-J., Namgung U.
J. Cell Sci. 120:246-255(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS CALD1 KINASE.
[6]"Cyclin-dependent kinase 1 plays a critical role in DNA replication control during rat liver regeneration."
Garnier D., Loyer P., Ribault C., Guguen-Guillouzo C., Corlu A.
Hepatology 50:1946-1956(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CYCLIN-A AND B1, INDUCTION BY MITOGEN AGENT, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X60767 mRNA. Translation: CAA43177.1.
BC091549 mRNA. Translation: AAH91549.1.
PIRS24913.
RefSeqNP_062169.1. NM_019296.1.
XP_006256415.1. XM_006256353.1.
UniGeneRn.6934.

3D structure databases

ProteinModelPortalP39951.
SMRP39951. Positions 1-294.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid248460. 1 interaction.
STRING10116.ENSRNOP00000000783.

PTM databases

PhosphoSiteP39951.

Proteomic databases

PaxDbP39951.
PRIDEP39951.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000000783; ENSRNOP00000000783; ENSRNOG00000000632.
GeneID54237.
KEGGrno:54237.
UCSCRGD:2319. rat.

Organism-specific databases

CTD983.
RGD2319. Cdk1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00720000108415.
HOVERGENHBG014652.
InParanoidP39951.
KOK02087.
OMAPNNDVWP.
OrthoDBEOG7966H8.
PhylomeDBP39951.
TreeFamTF101021.

Enzyme and pathway databases

BRENDA2.7.11.22. 5301.

Gene expression databases

GenevestigatorP39951.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio610684.
PROP39951.

Entry information

Entry nameCDK1_RAT
AccessionPrimary (citable) accession number: P39951
Secondary accession number(s): Q5BJB4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: April 16, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families