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P50613

Cyclin-dependent kinase 7


Function

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-terminus 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.


Database Links

Database Links
UniProt P50613
PDB 1LG3, 1PA8, 1UA2, 2HIC
BioGrid 107457
BindingDB P50613
DrugBank Not available
Guide to PHARMACOLOGY 1979
PharmGKB PA26314
KEGG hsa:1022
BioCyc Not available
Entrez Gene (GeneID) 1022

Chemical Space of the Positive Compounds


Model Performance Metrics

Metric Mean Value Standard Deviation
AUC 0.7781 0.0121
Accuracy 0.7 0.0105
Sensitivity 0.6964 0.0199
Specificity 0.6989 0.0241
BEDROC 0.8832 0.0186
MCC Threshold 0.596 N/A
MCC 0.4914 N/A
F-score Threshold 0.312 N/A
F-score 0.7554 N/A

Downloads

R Model Object

Random Forest model object (.RData)

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Positive Set

SMILES string + affinity value (.tsv)

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Page generated on: 2014-04-29 14:39:42