Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

CDK7 (P50613) - Overview - Molecular Target Synopsis

Protein


CDK7, Cyclin-dependent kinase 7
Enzyme Classification 2.7.11.22
UniProt P50613

Also Known as CDK7_HUMAN, CDK7, CAK, CAK1, CDKN7, MO15, STK1

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. Associates primarily with cyclin-H (CCNH) and MAT1 to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor; this complex is sensitive to UV light. The CAK complex binds to p53/TP53 in response to DNA damage. Interacts with CDK2, SF1/NR5A1, PUF60 and PRKCI.

1UA2
CRYSTAL STRUCTURE OF HUMAN CDK7
RCSB/PDB
Inspect Structure
See all 3D Structures for CDK7

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: CDK7 is active in the following subcellular-locations: cytoplasm, nucleus, perinuclear region.
GO terms: CDK7 is active in the following subcellular-locations: cyclin-dependent protein kinase activating kinase holoenzyme complex, cytoplasm, nucleoplasm, nucleus, perinuclear region of cytoplasm, transcription factor TFIIH holo complex, transcription factor TFIIK complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project CDK7 has gain in 0 cell-lines, loss in 2 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: NCI_H226, NCI_H522, SW_620

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MCAS, CAL-120, GTL-16

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, IMR-90, AG445

(see details)

RNA Interference


CDK7 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: PCI30, OAW42. (see details)

3D Structures


For CDK7 there are:
1 structures (4 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


CDK7 has been screened with 670 compounds (1026 bioactivities), 128 compounds have bioactivities that show binding affinity of <= 500nM (162 bioactivities). (see details)