- Protein Name
- Cyclin-dependent kinase 9
- Gene Name
- CDK9
- Organism
-
Homo sapiens
- 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.
| Site |
Maximum Consensus Site Population |
Minimum Consensus Site Population |
Median Consensus Site Population |
| MPP |
6 |
2 |
3.0 |
| DFG |
25 |
1 |
4.5 |
| PIF |
14 |
11 |
13.5 |
| DRS |
22 |
2 |
4.0 |
| DEF |
3 |
3 |
3.0 |
| EDI |
15 |
3 |
10.0 |
| MT3 |
13 |
1 |
3.0 |
| LBP |
20 |
3 |
11.5 |
| CMP |
15 |
2 |
4.0 |
| PDIG |
12 |
2 |
4.0 |
| ATP |
32 |
1 |
15.0 |
| PDB ID |
Maximum Consensus Site Population |
| MPP site |
DFG site |
PIF site |
DRS site |
DEF site |
EDI site |
MT3 site |
AAS site |
LBP site |
CMP site |
PDIG site |
ATP site |
PMP site |
| Total Druggable Structures per Site |
0 |
2 |
0 |
1 |
0 |
0 |
0 |
0 |
12 |
0 |
0 |
16 |
0 |
|
3BLR
|
3 |
0 |
0 |
0 |
3 |
14 |
0 |
0 |
11 |
10 |
12 |
23 |
0 |
|
4IMY
|
0 |
2 |
0 |
0 |
0 |
0 |
4 |
0 |
18 |
0 |
10 |
32 |
0 |
|
4BCJ
|
2 |
0 |
0 |
4 |
0 |
0 |
0 |
0 |
20 |
9 |
0 |
15 |
0 |
|
3MY1
|
3 |
0 |
0 |
4 |
0 |
0 |
4 |
0 |
19 |
0 |
3 |
15 |
0 |
|
4BCF
|
4 |
0 |
0 |
4 |
0 |
4 |
3 |
0 |
18 |
2 |
5 |
17 |
0 |
|
4OGR
|
0 |
9 |
14 |
0 |
0 |
0 |
0 |
0 |
18 |
0 |
5 |
30 |
0 |
|
3TNI
|
3 |
0 |
0 |
5 |
0 |
0 |
0 |
0 |
9 |
2 |
3 |
15 |
0 |
|
3TN8
|
3 |
0 |
0 |
11 |
0 |
0 |
0 |
0 |
13 |
5 |
2 |
18 |
0 |
|
3MIA
|
3 |
7 |
0 |
2 |
0 |
0 |
0 |
0 |
16 |
0 |
6 |
30 |
0 |
|
4OR5
|
2 |
0 |
14 |
0 |
0 |
10 |
0 |
0 |
19 |
15 |
0 |
26 |
0 |
|
3BLQ
|
2 |
0 |
0 |
6 |
0 |
15 |
13 |
0 |
8 |
4 |
4 |
16 |
0 |
|
4BCI
|
4 |
2 |
0 |
2 |
0 |
12 |
3 |
0 |
16 |
0 |
4 |
16 |
0 |
|
3MI9
|
5 |
16 |
0 |
2 |
0 |
0 |
0 |
0 |
17 |
0 |
0 |
26 |
0 |
|
3TNH
|
4 |
0 |
0 |
22 |
0 |
11 |
0 |
0 |
3 |
2 |
5 |
16 |
0 |
|
3BLH
|
3 |
2 |
11 |
11 |
0 |
0 |
0 |
0 |
13 |
9 |
4 |
16 |
0 |
|
3LQ5
|
6 |
1 |
0 |
3 |
0 |
3 |
2 |
0 |
19 |
0 |
2 |
27 |
0 |
|
AFP50750
|
0 |
25 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
4BCH
|
5 |
0 |
0 |
7 |
0 |
0 |
4 |
0 |
13 |
2 |
2 |
16 |
0 |
|
4EC8
|
3 |
0 |
0 |
0 |
0 |
0 |
2 |
0 |
14 |
0 |
5 |
15 |
0 |
|
4BCG
|
0 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
17 |
2 |
4 |
26 |
0 |
|
4EC9
|
2 |
0 |
13 |
3 |
0 |
11 |
0 |
0 |
17 |
0 |
3 |
25 |
0 |