Tchem CDK7 Cyclin-dependent kinase 7

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

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

IDG Partner Tools

GlyGen

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: 298.95   (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: 298.95   (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: 26

Tclin

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

Active Drug: 0

Active Ligands (26)

Explore Active Ligands

1 – 10 of 26

CHEMBL1230609

CDK7Tchem Kinase

Kd: 8.43

CHEMBL574738

CDK7Tchem Kinase

Kd: 8.35

CHEMBL445813

CDK7Tchem Kinase

Kd: 8.55

CHEMBL384304

CDK7Tchem Kinase

Kd: 9.24

CHEMBL2148120

CDK7Tchem Kinase

Kd: 7.89

CHEMBL393525

CDK7Tchem Kinase

Kd: 8.6

CHEMBL428690

CDK7Tchem Kinase

Kd: 7.64

RGB-286638

CDK7Tchem Kinase

IC50: 7.36000013

CHEMBL258805

CDK7Tchem Kinase

IC50: 6.03999996

milciclib

CDK7Tchem Kinase

IC50: 6.82000017

Protein Data Bank (4)

1 – 4 of 4

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

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (78)

Reactome (61)

KEGG (3)

PathwayCommons (8)

WikiPathways (6)

Cell Cycle (R-HSA-1640170)

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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

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

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

Publication Statistics

PubMed Score  298.95

PubMed score by year

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PubTator Score  203.14

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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Ortholog Sequence Conservation

WebLogo Color Code

PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

Compare across kinases on ProKinO

Structural Annotations

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UniProt Keyword Find Similar Targets

3D-structure
Acetylation
ATP-binding
Cell cycle
Cell division
Complete proteome
Cytoplasm
DNA damage
DNA repair
Kinase

MGI Phenotype Find Similar Targets

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