General Information of the Protein
Protein ID |
PT00926
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Protein Name |
Cyclin-dependent kinase 1
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Secondarily Protein Name |
Cell division control protein 2 homolog
Cell division protein kinase 1
p34 protein kinase
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Gene Name |
CDK1
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Secondarily Gene Name |
CDC2
CDC28A
CDKN1
P34CDC2
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Sequence |
MEDYTKIEKIGEGTYGVVYKGRHKTTGQVVAMKKIRLESEEEGVPSTAIREISLLKELRHPNIVSLQDVLMQDSRLYLIFEFLSMDLKKYLDSIPPGQYMDSSLVKSYLYQILQGIVFCHSRRVLHRDLKPQNLLIDDKGTIKLADFGLARAFGIPIRVYTHEVVTLWYRSPEVLLGSARYSTPVDIWSIGTIFAELATKKPLFHGDSEIDQLFRIFRALGTPNNEVWPEVESLQDYKNTFPKWKPGSLASHVKNLDENGLDLLSKMLIYDPAKRISGKMALNHPYFNDLDNQIKKM
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Organism |
Homo sapiens, Human
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Protein Classification |
Enzyme
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Kinase
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Protein Kinase
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CMGC protein kinase group
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CMGC protein kinase CDK family
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CMGC protein kinase CDC2 subfamily
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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 via association with multiple interphase cyclins (PubMed:16407259, PubMed:17459720, PubMed:16933150, PubMed:18356527, PubMed:19509060, PubMed:20171170, PubMed:19917720, PubMed:20937773, PubMed:20935635, PubMed:21063390, PubMed:23355470, PubMed:23601106, PubMed:23602554, PubMed:25556658, PubMed:26829474, PubMed:30704899). 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, KAT5, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MLST8, 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, TPPP, 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, SAMHD1, SIRT2, CGAS and RUNX2 (PubMed:16407259, PubMed:17459720, PubMed:16933150, PubMed:18356527, PubMed:19509060, PubMed:20171170, PubMed:19917720, PubMed:20937773, PubMed:20935635, PubMed:21063390, PubMed:23355470, PubMed:23601106, PubMed:23602554, PubMed:25556658, PubMed:32351706, PubMed:26829474, PubMed:30704899, PubMed:34741373). CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs (PubMed:18480403, PubMed:20360007). Essential for early stages of embryonic development (PubMed:18480403, PubMed:20360007). 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 (PubMed:18480403, PubMed:20360007). 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 (PubMed:18480403, PubMed:20360007). Phosphorylates KRT5 during prometaphase and metaphase (By similarity). 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 (PubMed:20360007). Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression (PubMed:20395957). 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 (PubMed:18356527). The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis (PubMed:16371510). 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 (PubMed:19509060). In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis (PubMed:20171170). The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis (PubMed:19917720). In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis (PubMed:20937773). This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes (PubMed:20937773). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration (By similarity). CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis (PubMed:26549230). Regulates the amplitude of the cyclic expression of the core clock gene BMAL1 by phosphorylating its transcriptional repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)-mediated ubiquitination and proteasomal degradation of NR1D1 (PubMed:27238018). Phosphorylates EML3 at 'Thr-881' which is essential for its interaction with HAUS augmin-like complex and TUBG1 (PubMed:30723163). Phosphorylates CGAS during mitosis, leading to its inhibition, thereby preventing CGAS activation by self DNA during mitosis (PubMed:32351706).
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Uniprot ID |
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Ensembl ID | |||||
HGNC ID | |||||
Subcellular Location |
Nucleus
Cytoplasm
Mitochondrion
Cytoplasm
Cytoskeleton
Microtubule organizing center
Centrosome
Cytoplasm
Cytoskeleton
Spindle
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Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein Protein Cell Line Compound Bioactivity Value: <= 0.1 μM > 0.1 μM and <= 10 μM > 10 μM Imprecise Activity |
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Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000007 , HT-29
Cell Line ID: CL000156 , HT-1080
Cell Line ID: CL000249 , OVCAR-3
Cell Line ID: CL000012 , Sf21
Biochemical Assays
Clinical Information about the Protein
Target 1 ( Cyclin-dependent kinase 1 (CDK1) )
Target Type | Clinical trial Target | ||||
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Disease | 10 Target-related Diseases | 10 | |||
1 | Breast cancer [ICD-11: 2C60-2C65] | ||||
2 | Mantle cell lymphoma [ICD-11: 2A85.5] | ||||
3 | Non-small-cell lung cancer [ICD-11: 2C25.Y] | ||||
4 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | ||||
5 | Graft rejection [ICD-11: NE84] | ||||
6 | Acute lymphoblastic leukaemia [ICD-11: 2A85] | ||||
7 | Small-cell lung cancer [ICD-11: 2C25.Y] | ||||
8 | Advanced solid tumour [ICD-11: 2A00-2F9Z] | ||||
9 | Obesity [ICD-11: 5B81] | ||||
10 | Pain [ICD-11: MG30-MG3Z] | ||||
Clinical Trial Drug(s) | 6 Clinical Trial Drugs | 6 | |||
1 | P-276 | Phase 2 | |||
2 | P276-00 | Phase 2 | |||
3 | R-roscovitine | Phase 2 | |||
4 | Ro 31-7453 | Phase 2 | |||
5 | AG-024322 | Phase 1 | |||
6 | PHA-793887 | Phase 1 | |||
Discontinued Drug(s) | 4 Discontinued Drugs | 4 | |||
1 | SCH 727965 | Discontinued in Phase 3 | |||
2 | BAY 10-00394 | Discontinued in Phase 2 | |||
3 | R547 | Discontinued in Phase 1 | |||
4 | CGP-60474 | Terminated | |||
Investigative Drug(s) | 1 Investigative Drug | 1 | |||
1 | Microxine | Investigative | |||
Patented Agent(s) | 1 Patented Agent | 1 | |||
1 | CHIR-99021 | Patented | |||
Preclinical Drug(s) | 1 Preclinical Drug | 1 | |||
1 | L-751250 | Preclinical |
Similar Protein(s) and Bioactivity Statistics
50% Identity
Protein ID | Protein Name | Protein Organism | |
PT06662 | Cyclin-dependent kinase 1 | Mus musculus, Mouse |
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