Names & Taxonomy

Uniprot ID:
P06493
Entry Name:
CDK1_HUMAN
Status:
reviewed
Protein Names:
Cyclin-dependent kinase 1 (CDK1) (EC 2.7.11.22) (EC 2.7.11.23) (Cell division control protein 2 homolog) (Cell division protein kinase 1) (p34 protein kinase)
Gene Names:
CDK1 CDC2 CDC28A CDKN1 P34CDC2
Gene Names Primary:
CDK1
Organism:
Homo sapiens (Human)

Structure

Length:
297
Sequence:
MEDYTKIEKIGEGTYGVVYKGRHKTTGQVVAMKKIRLESEEEGVPSTAIREISLLKELRHPNIVSLQDVLMQDSRLYLIFEFLSMDLKKYLDSIPPGQYMDSSLVKSYLYQILQGIVFCHSRRVLHRDLKPQNLLIDDKGTIKLADFGLARAFGIPIRVYTHEVVTLWYRSPEVLLGSARYSTPVDIWSIGTIFAELATKKPLFHGDSEIDQLFRIFRALGTPNNEVWPEVESLQDYKNTFPKWKPGSLASHVKNLDENGLDLLSKMLIYDPAKRISGKMALNHPYFNDLDNQIKKM
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Nucleus. Cytoplasm. Mitochondrion. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Cytoplasm, cytoskeleton, spindle. Note=Cytoplasmic during the interphase. Colocalizes with SIRT2 on centrosome during prophase and on splindle fibers during metaphase of the mitotic cell cycle. 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.

Function

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. CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis (PubMed:26549230).
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.; ATP + = ADP + phosphate.
Enzyme Regulation:
ENZYME REGULATION: Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-161 activates it. Activated through a multistep process; binding to cyclin-B is required for relocation of cyclin-kinase complexes to the nucleus, activated by CAK/CDK7-mediated phosphorylation on Thr-161, and CDC25-mediated dephosphorylation of inhibitory phosphorylation on Thr-14 and Tyr-15. Inhibited by flavopiridol and derivatives, pyrimidine derivatives, pyridine derivatives, purine derivatives, staurosporine, paullones, oxoindoles, indazole analogs, indolin-2-ones, pyrazolopyridines, imidazopyridine (AZ703), thiazolinone analogs(RO-3306), thiazol urea, macrocyclic quinoxalin-2-one, pyrrolocarbazole, pyrazolo-1,3,5-triazine, pyrazolopyrimidine (Dinaciclib, SCH 727965), 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine), olomoucine, AG-024322, AT-7519, P276-00, R547/Ro-4584820 and SNS-032/BMS-387032. Repressed by the CDK inhibitors CDKN1A/p21 and CDKN1B/p27 during the G1 phase and by CDKN1A/p21 at the G1-S checkpoint upon DNA damage. Transient activation by rapid and transient dephosphorylation at Tyr-15 triggered by TGFB1.
Active Site:
ACT_SITE 128 128 Proton acceptor.
Gene Ontology Go:
centrosome
cytoplasm
cytosol
extracellular exosome
membrane
midbody
mitochondrion
mitotic spindle
nuclear chromosome, telomeric region
nucleoplasm
nucleus
spindle microtubule
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
activation of MAPK activity
anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
apoptotic process
cell aging
cell division
cell migration
cellular response to hydrogen peroxide
centrosome cycle
chromosome condensation
DNA repair
DNA replication
epithelial cell differentiation
G1/S transition of mitotic cell cycle
G2/M transition of mitotic cell cycle
Golgi disassembly
microtubule cytoskeleton organization
mitotic cell cycle
mitotic G2 DNA damage checkpoint
mitotic nuclear division
mitotic nuclear envelope disassembly
negative regulation of apoptotic process
organ regeneration
organelle organization
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
positive regulation of cardiac muscle cell proliferation
positive regulation of DNA replication
positive regulation of gene expression
positive regulation of mitotic cell cycle
positive regulation of protein import into nucleus, translocation
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 complex assembly
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
response to activity
response to amine
response to axon injury
response to cadmium ion
response to copper ion
response to drug
response to ethanol
response to organic cyclic compound
response to toxic substance
ventricular cardiac muscle cell development
Gene Ontology Biological Process:
activation of MAPK activity
anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
apoptotic process
cell aging
cell division
cell migration
cellular response to hydrogen peroxide
centrosome cycle
chromosome condensation
DNA repair
DNA replication
epithelial cell differentiation
G1/S transition of mitotic cell cycle
G2/M transition of mitotic cell cycle
Golgi disassembly
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
organ regeneration
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
positive regulation of cardiac muscle cell proliferation
positive regulation of DNA replication
positive regulation of gene expression
positive regulation of mitotic cell cycle
positive regulation of protein import into nucleus, translocation
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 complex assembly
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
response to activity
response to amine
response to axon injury
response to cadmium ion
response to copper ion
response to drug
response to ethanol
response to organic cyclic compound
response to toxic substance
ventricular cardiac muscle cell development
Gene Ontology Molecular Function:
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
Gene Ontology Cellular Component:
centrosome
cytoplasm
cytosol
extracellular exosome
membrane
midbody
mitochondrion
mitotic spindle
nuclear chromosome, telomeric region
nucleoplasm
nucleus
spindle microtubule
Keywords:
3D-structure
ATP-binding
Acetylation
Alternative splicing
Apoptosis
Cell cycle
Cell division
Complete proteome
Cytoplasm
Cytoskeleton
Isopeptide bond
Kinase
Mitochondrion
Mitosis
Nucleotide-binding
Nucleus
Phosphoprotein
Reference proteome
Serine/threonine-protein kinase
Transferase
Ubl conjugation
Interacts With:
P03070; P14635; P30307; P38936; P61024; P19525; Q12778; O95835; Q99640; P0CG48

Publication

PubMed ID:
3553962 9515786 14702039 15164054 15489334 3289755 7569953 9242535 9030781 12775724 15145941 16407259 16371510 18056467 17459720 16933150 18220336 18480403 18691976 18669648 18655026 18356527 19509060 19369195 19690332 19608861 20171170 20395957 19917613 20360007 19917720 20937773 20935635 20068231 21269460 21406398 21063390 16236519 19364923 19238148 21535261 21517772 21655336 21406692 22814378 26549230 25944712