Tchem CDK7 Cyclin-dependent kinase 7

Protein Summary

Description

Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Phosphorylation of POLR2A in complex with DNA promotes transcription initiation by triggering dissociation from DNA. Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition. The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression. This protein forms a trimeric complex with cyclin H and MAT1, which functions as a Cdk-activating kinase (CAK). It is an essential component of the transcription factor TFIIH, that is involved in transcription initiation and DNA repair. This protein is thought to serve as a direct link between the regulation of transcription and the cell cycle. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P50613
• Q9BS60
• Q9UE19

Gene Name

• CDK7

Ensembl ID

• ENST00000256443
• ENSP00000256443
• ENSG00000134058
• ENST00000615305
• ENSP00000479116
• ENSG00000277273

Symbol

• CAK
• CAK1
• CDKN7
• MO15
• STK1
• CAK
• CAK1
• HCAK
• MO15
• STK1
• CDKN7
• p39MO15

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
small molecule	1
biological process	0.95
hub protein	0.88
transcription factor perturbation	0.88

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Tyrosine Protein Kinase / Cyclin-dependent Kinase 7

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Cyclin-dependent Kinase 7

DTO Classes

Protein / Kinase / Protein Kinase / Cmgc Group / Cdk Family / Cdk7 Subfamily / Cyclin-dependent Kinase 7

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: 305.05   (req: < 5)

Gene RIFs: 42   (req: <= 3)

Antibodies: 756   (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: 305.05   (req: >= 5)

Gene RIFs: 42   (req: > 3)

Antibodies: 756   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 28

Tchem

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

Active Ligands: 56

Tclin

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

Active Drug: 1

Expression Data (0 Tissues)

tutorial

No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

Find Targets by Sequence

Show Full Sequence

ProtVista Viewer

Related Tools (5)

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.

Go To Tool

Target Illumination GWAS Analytics (TIGA)

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

Go To Tool

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.

Go To Tool

GlyGen

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

Go To Tool

ARCHS4

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

Go To Tool

Approved Drugs (1)

Explore Approved Drugs

1 – 1 of 1

trilaciclib

CDK7Tchem Kinase

INHIBITOR pKd : 9.57

Active Ligands (56)

Explore Active Ligands

1 – 10 of 56

foretinib

CDK7Tchem Kinase

pKd : 7.92

AST-487

CDK7Tchem Kinase

pKd : 7.77

CHEMBL4568087

CDK7Tchem Kinase

pIC50 : 8.89

SID103904462

CDK7Tchem Kinase

pKi : 9.2

RGB-286638

CDK7Tchem Kinase

pKd : 8.52

SID103904605

CDK7Tchem Kinase

pKi : 7.7

SID103904479

CDK7Tchem Kinase

pKi : 9

SID103904480

CDK7Tchem Kinase

pKi : 8.4

SID103904192

CDK7Tchem Kinase

pKi : 8.3

AT-7519

CDK7Tchem Kinase

pKd : 8.1

Protein-Protein Interactions (345)

Explore Interacting Targets

1 – 10 of 345

• See Interactions on String-DB

CCNH

Tbio

Novelty:  0.00693072

p_int:  1

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

MNAT1

Tbio

Family:  Enzyme

Novelty:  0.02484936

p_int:  0.999999996

p_ni:  4e-9

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

HSP90AB3P

Tdark

p_int:  0.999996978

p_ni:  0.00000302

p_wrong:  1e-9

Data Source:  BioPlex

HSP90AA4P

Tdark

p_int:  0.999995149

p_ni:  0.000004819

p_wrong:  3.1e-8

Data Source:  BioPlex

HSP90AB4P

Tdark

p_int:  0.999993981

p_ni:  0.000006018

p_wrong:  1e-9

Data Source:  BioPlex

PI4KB

Tchem

Family:  Kinase

Novelty:  0.00856875

p_int:  0.99999293

p_ni:  0.00000707

Score:  0.215

Data Source:  BioPlex,STRINGDB

TBC1D32

Tbio

Novelty:  0.25744084

p_int:  0.999839557

p_ni:  0.000160425

p_wrong:  1.8e-8

Score:  0.362

Data Source:  BioPlex,STRINGDB

CDK20

Tbio

Family:  Kinase

Novelty:  0.01176977

p_int:  0.999814764

p_ni:  0.000171931

p_wrong:  0.000013304

Score:  0.291

Data Source:  BioPlex,STRINGDB

FKBP5

Tchem

Family:  Enzyme

Novelty:  0.00214511

p_int:  0.999788021

p_ni:  0.000211979

Score:  0.164

Data Source:  BioPlex,STRINGDB

HSP90AA5P

Tdark

p_int:  0.998788403

p_ni:  0.001211597

Data Source:  BioPlex

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (78)

Reactome (61)

KEGG (3)

PathwayCommons (8)

WikiPathways (6)

Cell Cycle (R-HSA-1640170)

Click on a row in the table to change the structure displayed.

Find Similar Targets

Items per page:

5

1 – 5 of 61

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cell Cycle	597 targets	R-HSA-1640170
Reactome	Cell Cycle, Mitotic	495 targets	R-HSA-69278
Reactome	Cyclin A/B1/B2 associated events during G2/M transition	25 targets	R-HSA-69273
Reactome	Cyclin A:Cdk2-associated events at S phase entry	86 targets	R-HSA-69656
Reactome	Cyclin D associated events in G1	45 targets	R-HSA-69231

Name	Explore in Pharos	Explore in Source
Cell Cycle	597 targets	R-HSA-1640170
Cell Cycle, Mitotic	495 targets	R-HSA-69278
Cyclin A/B1/B2 associated events during G2/M transition	25 targets	R-HSA-69273
Cyclin A:Cdk2-associated events at S phase entry	86 targets	R-HSA-69656
Cyclin D associated events in G1	45 targets	R-HSA-69231

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (35)

Functions (10)

Components (7)

Processes (18)

Find Similar Targets

Items per page:

10

1 – 10 of 10

GO Term	Evidence	Assigned by
DNA-dependent ATPase activity	Inferred from Direct Assay (IDA)	UniProtKB
RNA polymerase II CTD heptapeptide repeat kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
protein C-terminus binding	Inferred from Physical Interaction (IPI)	UniProtKB
cyclin-dependent protein serine/threonine kinase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
kinase activity	Traceable Author Statement (TAS)	Reactome
protein kinase activity	Traceable Author Statement (TAS)	ProtInc
protein serine/threonine kinase activity	Traceable Author Statement (TAS)	Reactome
androgen receptor binding	Non-traceable Author Statement (NAS)	UniProtKB
transcription coactivator activity	Non-traceable Author Statement (NAS)	UniProtKB
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations (null)

No disease associations found

GWAS Traits (12)

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 12

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
neutrophil count	EFO_0004833	3	3	3		94.3
myeloid white cell count	EFO_0007988	2	2	2		90.1
leukocyte count	EFO_0004308	2	2	2		86.1
neutrophil percentage of leukocytes	EFO_0007990	2	2	2		83.7
sum of basophil and neutrophil counts	EFO_0009388	1	1	1		64.9

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 12

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
neutrophil count	EFO_0004833	3		94.3
myeloid white cell count	EFO_0007988	2		90.1
leukocyte count	EFO_0004308	2		86.1
neutrophil percentage of leukocytes	EFO_0007990	2		83.7
sum of basophil and neutrophil counts	EFO_0009388	1		64.9

Reset Zoom  Beta Count   Odds Ratio

Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
ATP-binding
Cell cycle
Cell division
Complete proteome
Cytoplasm
DNA damage
DNA repair
Kinase

GWAS Trait Find Similar Targets

No Header	No Header
glomerular filtration rate
granulocyte count
granulocyte percentage of myeloid white cells
leukocyte count
lymphocyte percentage of leukocytes
monocyte percentage of leukocytes
myeloid white cell count
neutrophil count
neutrophil percentage of leukocytes
sum of basophil and neutrophil counts

MGI Phenotype Find Similar Targets

No Header	No Header
adipose tissue phenotype
cellular phenotype
digestive/alimentary phenotype
embryo phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
integument phenotype
mortality/aging
pigmentation phenotype

IDG Resources

No IDG generated resources found

Orthologs (17)

1 – 5 of 17

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cyclin dependent kinase 7	VGNC:11877	462378
Macaque	cyclin dependent kinase 7		699871
Mouse	cyclin-dependent kinase 7	MGI:102956	12572
Rat	cyclin-dependent kinase 7	RGD:621124	171150
Dog	cyclin dependent kinase 7	VGNC:39060	608441

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cyclin dependent kinase 7
Macaque	cyclin dependent kinase 7
Mouse	cyclin-dependent kinase 7
Rat	cyclin-dependent kinase 7
Dog	cyclin dependent kinase 7

Publication Statistics

PubMed Score 305.05

PubMed score by year

Reset Zoom

PubTator Score 203.14

PubTator score by year

Reset Zoom

Patents

Patents by year

Reset Zoom

Related Publications

Text Mined References (130)

GeneRif Annotations (42)

Items per page:

10

0 of 0

PMID	Year	Title