Target name

P50750: Cyclin-dependent kinase 9


  Protein function

Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR, and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation.

  Database links

Uniprot primary ID P50750
PDB ID 3BLR 3BLQ 4IMY 4EC8 4BCJ 4BCI 3TN8 4BCG 4BCF 1PF6 4BCH 4OGR 3MI9 4OR5 3TNI 3TNH 3MIA 3LQ5 3BLH 3MY1 4EC9
DrugBank ID
BioGrid ID 107459
GuidetoPHARMACOLOGY ID 1981
PharmGKB ID PA26316
KEGG ID hsa:1025
DIP ID DIP-29016N
STRING ID 9606.ENSP00000362361
IntAct ID P50750
DMDM 68067660
BRENDA 2.7.11.22 2.7.11.23
Reactome R-HSA-167238 R-HSA-112382 R-HSA-176034 R-HSA-167152 R-HSA-167243 R-HSA-167200 R-HSA-2173796 R-HSA-167246 R-HSA-167287 R-HSA-167290 R-HSA-75955 R-HSA-674695
SignaLink P50750
BioCyc
Entrez Gene (Gene ID) 1025
BindingDB P50750

  Model Performance Metrics

Fingerprint type Sensitivity SEN_std Specificity SPE_std Accuracy ACC_std F1-score F1-score_std AUC AUC_std MCC MCC_std Download model
FP2 fingerprints 0.671 0.009 0.997 0.000 0.834 0.005 0.801 0.003 0.930 0.000 0.704 0.005 Download
Estate fingerprints 0.851 0.006 0.863 0.009 0.857 0.007 0.857 0.007 0.924 0.005 0.717 0.011 Download
MACCS fingerprints 0.859 0.009 0.871 0.009 0.865 0.007 0.865 0.007 0.927 0.005 0.730 0.013 Download
Daylight fingerprints 0.717 0.011 0.983 0.000 0.850 0.007 0.827 0.011 0.905 0.005 0.727 0.011 Download
ECFP2 fingerprints 0.854 0.011 0.938 0.009 0.896 0.007 0.892 0.009 0.950 0.000 0.795 0.016 Download
ECFP4 fingerprints 0.838 0.008 0.964 0.009 0.901 0.003 0.895 0.007 0.950 0.000 0.810 0.011 Download
ECFP6 fingerprints 0.819 0.003 0.979 0.004 0.899 0.003 0.889 0.003 0.950 0.000 0.809 0.003 Download

  Download datasets

Positive dataset Negative dataset


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 E-mail: biomed@csu.edu.cn