Tchem CDK1 Cyclin-dependent kinase 1

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Tyrosine Protein Kinase / Cyclin-dependent Kinase 1

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Cyclin-dependent Kinase 1

Protein Summary

Description

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, SAMHD1, 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). (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G1/S and G2/M phase transitions of eukaryotic cell cycle. Mitotic cyclins stably associate with this protein and function as regulatory subunits. The kinase activity of this protein is controlled by cyclin accumulation and destruction through the cell cycle. The phosphorylation and dephosphorylation of this protein also play important regulatory roles in cell cycle control. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

Uniprot Accession IDs

• P06493
• A8K7C4
• C9J497
• O60764
• CDK1

Gene Name

• CDK1

Ensembl ID

• ENST00000316629
• ENSP00000325970
• ENSG00000170312
• ENST00000373809
• ENSP00000362915
• ENST00000395284
• ENSP00000378699

Symbol

• CDC2
• CDC28A
• CDKN1
• P34CDC2
• CDC2
• CDC28A
• P34CDC2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
chemical	1
hub protein	1
interacting protein	1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1891.67   (req: < 5)

Gene RIFs: 351   (req: <= 3)

Antibodies: 2457   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1891.67   (req: >= 5)

Gene RIFs: 351   (req: > 3)

Antibodies: 2457   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 59

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 199

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Active Ligands (199)

Explore Active Ligands

1 – 10 of 199

CHEMBL388978

CDK1Tchem Kinase

IC50: 9.4

CHEMBL445813

CDK1Tchem Kinase

IC50: 6.67999983

CHEMBL384304

CDK1Tchem Kinase

Ki: 8.69999981

voruciclib

CDK1Tchem Kinase

IC50: 7.5999999

RGB-286638

CDK1Tchem Kinase

IC50: 8.69999981

CHEMBL1236539

CDK1Tchem Kinase

IC50: 7.30000019

CHEMBL191003

CDK1Tchem Kinase

IC50: 8.22

CHEMBL2103840

CDK1Tchem Kinase

IC50: 8.52000046

CHEMBL258805

CDK1Tchem Kinase

IC50: 7.4000001

milciclib

CDK1Tchem Kinase

IC50: 5.92000008

Protein Data Bank (6)

1 – 5 of 6

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (109)

Reactome (71)

KEGG (8)

PathwayCommons (16)

WikiPathways (14)

APC/C-mediated degradation of cell cycle proteins (R-HSA-174143)

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Items per page:

5

1 – 5 of 71

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	APC/C-mediated degradation of cell cycle proteins	87 targets	R-HSA-174143
Reactome	APC/C:Cdc20 mediated degradation of Cyclin B	23 targets	R-HSA-174048
Reactome	APC/C:Cdc20 mediated degradation of mitotic proteins	76 targets	R-HSA-176409
Reactome	APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	74 targets	R-HSA-179419
Reactome	AURKA Activation by TPX2	72 targets	R-HSA-8854518

Name	Explore in Pharos	Explore in Source
APC/C-mediated degradation of cell cycle proteins	87 targets	R-HSA-174143
APC/C:Cdc20 mediated degradation of Cyclin B	23 targets	R-HSA-174048
APC/C:Cdc20 mediated degradation of mitotic proteins	76 targets	R-HSA-176409
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	74 targets	R-HSA-179419
AURKA Activation by TPX2	72 targets	R-HSA-8854518

Gene Ontology Terms (75)

Functions (11)

Components (16)

Processes (48)

Items per page:

10

1 – 10 of 11

GO Term	Evidence	Assigned by
cyclin binding	Inferred from Direct Assay (IDA)	MGI
cyclin-dependent protein kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
cyclin-dependent protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
histone kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
protein kinase activity	Inferred from Direct Assay (IDA)	MGI
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
RNA polymerase II CTD heptapeptide repeat kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
chromatin binding	Inferred from Electronic Annotation (IEA)	Ensembl
Hsp70 protein binding	Inferred from Electronic Annotation (IEA)	Ensembl

Protein-Protein Interactions (979)

Explore Interacting Targets

1 – 10 of 979

• See Interactions on String-DB

CKS1B

Tbio

Family: Enzyme

Novelty: 0.00986309

p_int: 1

Score: 0.999

Data Source: BioPlex,STRINGDB

CKS2

Tbio

Family: Enzyme

Novelty: 0.03208125

p_int: 1

Score: 0.999

Data Source: BioPlex,STRINGDB

CCNA2

Tchem

Novelty: 0.00061948

p_int: 0.999999958

p_ni: 4.2e-8

Score: 0.999

Data Source: BioPlex,Reactome,STRINGDB

CCNB2

Tbio

Novelty: 0.01021878

p_int: 0.999997675

p_ni: 0.000002325

p_wrong: 1e-9

Score: 0.999

Data Source: BioPlex,Reactome,STRINGDB

CCNB1

Tchem

Novelty: 0.00068627

p_int: 0.999990498

p_ni: 0.000009502

Score: 0.999

Data Source: BioPlex,Reactome,STRINGDB

PKMYT1

Tchem

Family: Kinase

Novelty: 0.04783054

p_int: 0.999934141

p_ni: 0.000065858

Score: 0.996

Data Source: BioPlex,Reactome,STRINGDB

SKP2

Tbio

Family: Enzyme

Novelty: 0.00202287

p_int: 0.999430446

p_ni: 0.000569554

Score: 0.935

Data Source: BioPlex,STRINGDB

CDK3

Tchem

Family: Kinase

Novelty: 0.04846001

p_int: 0.998703285

p_ni: 0.001296715

Score: 0.878

Data Source: BioPlex,STRINGDB

CDT1

Tbio

Novelty: 0.00565545

p_int: 0.998630143

p_ni: 0.001320007

p_wrong: 0.00004985

Score: 0.99

Data Source: BioPlex,STRINGDB

CDKN1B

Tbio

Family: Enzyme

Novelty: 0.00079036

p_int: 0.998168939

p_ni: 0.001831061

Score: 0.964

Data Source: BioPlex,STRINGDB

Publication Statistics

PubMed Score  1891.67

PubMed score by year

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PubTator Score  2343.37

PubTator score by year

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Patents

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Amino Acid Sequence

Residue Counts

Sequence

MEDYTKIEKIGEGTYGVVYKGRHKTTGQVVAMKKIRLESEEEGVPSTAIREISLLKELRHPNIVSLQDVL

1-70

MQDSRLYLIFEFLSMDLKKYLDSIPPGQYMDSSLVKSYLYQILQGIVFCHSRRVLHRDLKPQNLLIDDKG

70-140

TIKLADFGLARAFGIPIRVYTHEVVTLWYRSPEVLLGSARYSTPVDIWSIGTIFAELATKKPLFHGDSEI

140-210

DQLFRIFRALGTPNNEVWPEVESLQDYKNTFPKWKPGSLASHVKNLDENGLDLLSKMLIYDPAKRISGKM

210-280

ALNHPYFNDLDNQIKKM

280-297

MEDYTKIEKIGEGTYGVVYKGRHKTTGQVVAMKKIRLESEEEGVPSTAIREISLLKELRHPNIVSLQDVLMQDSRLYLIFEFLSMDLKKYLDSIPPGQYMDSSLVKSYLYQILQGIVFCHSRRVLHRDLKPQNLLIDDKGTIKLADFGLARAFGIPIRVYTHEVVTLWYRSPEVLLGSARYSTPVDIWSIGTIFAELATKKPLFHGDSEIDQLFRIFRALGTPNNEVWPEVESLQDYKNTFPKWKPGSLASHVKNLDENGLDLLSKMLIYDPAKRISGKMALNHPYFNDLDNQIKKM

Find similar targets by:

Uniprot Keyword

3D-structure
Acetylation
Alternative splicing
Apoptosis
ATP-binding
Cell cycle
Cell division
Complete proteome
Cytoplasm
Cytoskeleton