Tchem CDK1 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

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

DTO Classes

Protein / Kinase / Protein Kinase / Cmgc Group / Cdk Family / Cdk1 Subfamily / Cyclin-dependent Kinase 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: 2423.64   (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: 2423.64   (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: 216

Tclin

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

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (216)

Explore Active Ligands

1 – 10 of 216

staurosporine

CDK1Tchem Kinase

pKd : 7.89

SID103905531

CDK1Tchem Kinase

pKi : 9.5

SID103904595

CDK1Tchem Kinase

pKi : 8.2

SID103904592

CDK1Tchem Kinase

pKi : 8

SID103904953

CDK1Tchem Kinase

pKi : 7.9

RGB-286638

CDK1Tchem Kinase

pKd : 8.52

SID103904192

CDK1Tchem Kinase

pKi : 8.3

AT-7519

CDK1Tchem Kinase

pKd : 8.1

G&ouml; 6976

CDK1Tchem Kinase

pKi : 7.8

R547

CDK1Tchem Kinase

pKd : 9.27

Protein-Protein Interactions (979)

Explore Interacting Targets

1 – 10 of 979

• See Interactions on String-DB

CKS1B

Tbio

Family:  Enzyme

Novelty:  0.00766779

p_int:  1

Score:  0.999

Data Source:  BioPlex,STRINGDB

CKS2

Tbio

Family:  Enzyme

Novelty:  0.02482411

p_int:  1

Score:  0.999

Data Source:  BioPlex,STRINGDB

CCNA2

Tchem

Novelty:  0.00049887

p_int:  0.999999958

p_ni:  4.2e-8

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

CCNB2

Tbio

Novelty:  0.00672914

p_int:  0.999997675

p_ni:  0.000002325

p_wrong:  1e-9

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

CCNB1

Tchem

Novelty:  0.0005503

p_int:  0.999990498

p_ni:  0.000009502

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

PKMYT1

Tchem

Family:  Kinase

Novelty:  0.03025516

p_int:  0.999934141

p_ni:  0.000065858

Score:  0.996

Data Source:  BioPlex,Reactome,STRINGDB

SKP2

Tbio

Family:  Enzyme

Novelty:  0.00182658

p_int:  0.999430446

p_ni:  0.000569554

Score:  0.935

Data Source:  BioPlex,STRINGDB

CDK3

Tchem

Family:  Kinase

Novelty:  0.03380289

p_int:  0.998703285

p_ni:  0.001296715

Score:  0.878

Data Source:  BioPlex,STRINGDB

CDT1

Tbio

Novelty:  0.00398013

p_int:  0.998630143

p_ni:  0.001320007

p_wrong:  0.00004985

Score:  0.99

Data Source:  BioPlex,STRINGDB

CDKN1B

Tbio

Family:  Enzyme

Novelty:  0.00069449

p_int:  0.998168939

p_ni:  0.001831061

Score:  0.964

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (15)

Explore Nearest Tclin Targets

Upstream (6)

Downstream (9)

1 – 5 of 6

CALM1

Tclin

Family:  Other

KEGG Distance:  3

Common Pathways:  3

1: Oocyte meiosis

2: Human immunodeficiency virus 1 infection

3: Cellular senescence

CALM3

Tclin

Family:  Other

KEGG Distance:  3

Common Pathways:  3

1: Oocyte meiosis

2: Human immunodeficiency virus 1 infection

3: Cellular senescence

CALM2

Tclin

Family:  Other

KEGG Distance:  3

Common Pathways:  3

1: Oocyte meiosis

2: Human immunodeficiency virus 1 infection

3: Cellular senescence

AR

Tclin

Family:  Nuclear Receptor

KEGG Distance:  3

Common Pathways:  1

1: Oocyte meiosis

IGF1R

Tclin

Family:  Kinase

KEGG Distance:  3

Common Pathways:  2

1: Oocyte meiosis

2: Progesterone-mediated oocyte maturation

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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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

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (75)

Functions (11)

Components (16)

Processes (48)

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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

Disease Associations ()

No disease associations found

GWAS Traits (1)

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5

1 – 1 of 1

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
heel bone mineral density	EFO_0009270	2	1	2		29.9

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
heel bone mineral density	EFO_0009270	2		29.9

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Apoptosis
ATP-binding
Cell cycle
Cell division
Complete proteome
Cytoplasm
Cytoskeleton

GWAS Trait Find Similar Targets

No Header	No Header
heel bone mineral density

MGI Phenotype Find Similar Targets

No Header	No Header
cellular phenotype
embryo phenotype
endocrine/exocrine gland phenotype
homeostasis/metabolism phenotype
liver/biliary system phenotype
mortality/aging
neoplasm
reproductive system phenotype
vision/eye phenotype

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cyclin dependent kinase 1	VGNC:7843	450481
Macaque	cyclin dependent kinase 1		699269
Mouse	cyclin-dependent kinase 1	MGI:88351	12534
Rat	cyclin-dependent kinase 1	RGD:2319	54237
Dog	cyclin dependent kinase 1	VGNC:39042	100856079

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cyclin dependent kinase 1
Macaque	cyclin dependent kinase 1
Mouse	cyclin-dependent kinase 1
Rat	cyclin-dependent kinase 1
Dog	cyclin dependent kinase 1

Publication Statistics

PubMed Score 2423.64

PubMed score by year

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PubTator Score 2343.37

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Related Publications

Text Mined References (604)

GeneRif Annotations (351)

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PMID	Year	Title