General Information of the Protein
Protein ID |
PT01235
|
||||
---|---|---|---|---|---|
Protein Name |
Cyclin-dependent kinase 9
|
||||
Secondarily Protein Name |
C-2K
Cell division cycle 2-like protein kinase 4
Cell division protein kinase 9
Serine/threonine-protein kinase PITALRE
Tat-associated kinase complex catalytic subunit
|
||||
Gene Name |
CDK9
|
||||
Secondarily Gene Name |
CDC2L4
TAK
|
||||
Sequence |
MAKQYDSVECPFCDEVSKYEKLAKIGQGTFGEVFKARHRKTGQKVALKKVLMENEKEGFPITALREIKILQLLKHENVVNLIEICRTKASPYNRCKGSIYLVFDFCEHDLAGLLSNVLVKFTLSEIKRVMQMLLNGLYYIHRNKILHRDMKAANVLITRDGVLKLADFGLARAFSLAKNSQPNRYTNRVVTLWYRPPELLLGERDYGPPIDLWGAGCIMAEMWTRSPIMQGNTEQHQLALISQLCGSITPEVWPNVDNYELYEKLELVKGQKRKVKDRLKAYVRDPYALDLIDKLLVLDPAQRIDSDDALNHDFFWSDPMPSDLKGMLSTHLTSMFEYLAPPRRKGSQITQQSTNQSRNPATTNQTEFERVF
Show/Hide
|
||||
Organism |
Homo sapiens, Human
|
||||
Protein Classification |
Enzyme
>
Kinase
>
Protein Kinase
>
CMGC protein kinase group
>
CMGC protein kinase CDK family
>
CMGC protein kinase CDK9 subfamily
|
||||
Function |
Protein kinase involved in the regulation of transcription (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094, PubMed:29335245). 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 (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094, PubMed:30134174). This complex is inactive when in the 7SK snRNP complex form (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094). Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR and the negative elongation factors DSIF and NELFE (PubMed:9857195, PubMed:10912001, PubMed:11112772, PubMed:12037670, PubMed:20081228, PubMed:20980437, PubMed:21127351). 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) (PubMed:17956865, PubMed:18362169). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis (PubMed:10393184, PubMed:11112772). P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export (PubMed:15564463, PubMed:19575011, PubMed:19844166). 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 (PubMed:15564463, PubMed:19575011, PubMed:19844166). 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 (PubMed:21127351). 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 (PubMed:20493174). In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6 (PubMed:20493174). Promotes cardiac myocyte enlargement (PubMed:20081228). RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription (PubMed:21127351). AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect (PubMed:9857195, PubMed:10912001, PubMed:11112772). The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation (PubMed:12037670). Catalyzes phosphorylation of KAT5, promoting KAT5 recruitment to chromatin and histone acetyltransferase activity (PubMed:29335245).
Show/Hide
|
||||
Uniprot ID |
Show/Hide
|
||||
Ensembl ID | |||||
HGNC ID | |||||
Subcellular Location |
Nucleus
Cytoplasm
Nucleus
PML body
|
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein Protein Cell Line Compound Bioactivity Value: <= 0.1 μM > 0.1 μM and <= 10 μM > 10 μM Imprecise Activity |
|
---|
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000052 , A-431
Cell Line ID: CL000067 , HCT 116
Cell Line ID: CL000083 , MCF-7
Cell Line ID: CL000091 , MV4-11
Biochemical Assays
Clinical Information about the Protein
Target 1 ( Cyclin-dependent kinase 9 (CDK9) )
Target Type | Clinical trial Target | ||||
---|---|---|---|---|---|
Disease | 8 Target-related Diseases | 8 | |||
1 | Mantle cell lymphoma [ICD-11: 2A85.5] | ||||
2 | Haematological malignancy [ICD-11: 2B33.Y] | ||||
3 | Lymphoma [ICD-11: 2A80-2A86] | ||||
4 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | ||||
5 | Non-hodgkin lymphoma [ICD-11: 2B33.5] | ||||
6 | Acute myeloid leukaemia [ICD-11: 2A60] | ||||
7 | Acute lymphoblastic leukaemia [ICD-11: 2A85] | ||||
8 | Small-cell lung cancer [ICD-11: 2C25.Y] | ||||
Clinical Trial Drug(s) | 7 Clinical Trial Drugs | 7 | |||
1 | P276-00 | Phase 2 | |||
2 | AZD4573 | Phase 1 | |||
3 | CYC065 | Phase 1 | |||
4 | SNS-032 | Phase 1 | |||
5 | TP-1287 | Phase 1 | |||
6 | VIP-152 | Phase 1 | |||
7 | Flavopiridol | Phase 2 | |||
Discontinued Drug(s) | 2 Discontinued Drugs | 2 | |||
1 | SCH 727965 | Discontinued in Phase 3 | |||
2 | BAY 10-00394 | Discontinued in Phase 2 |