Overview
| Uniprot ID | P50750 |
|---|
| Protein Name | Cyclin-dependent kinase 9 |
|---|
| Gene Name | CDK9 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 345 |
YLAPPRRKGSQITQQ |
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:16427012, 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:10912001, PubMed:11112772, PubMed:12037670, PubMed:16427012, PubMed:20081228, PubMed:20980437, PubMed:21127351, PubMed:9857195). 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, PubMed:28539972). 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). Also catalyzes phosphorylation of histone H1.4 (H1-4) at Ser-187' (H1.4S187Ph), a modification associated with transcription activation (PubMed:28539972). 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:10912001, PubMed:11112772, PubMed:9857195). 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)
Protein Sequence
10
MAKQYDSVEC
20
PFCDEVSKYE
30
KLAKIGQGTF
40
GEVFKARHRK
50
TGQKVALKKV
60
LMENEKEGFP
70
ITALREIKIL
80
QLLKHENVVN
90
LIEICRTKAS
100
PYNRCKGSIY
110
LVFDFCEHDL
120
AGLLSNVLVK
130
FTLSEIKRVM
140
QMLLNGLYYI
150
HRNKILHRDM
160
KAANVLITRD
170
GVLKLADFGL
180
ARAFSLAKNS
190
QPNRYTNRVV
200
TLWYRPPELL
210
LGERDYGPPI
220
DLWGAGCIMA
230
EMWTRSPIMQ
240
GNTEQHQLAL
250
ISQLCGSITP
260
EVWPNVDNYE
270
LYEKLELVKG
280
QKRKVKDRLK
290
AYVRDPYALD
300
LIDKLLVLDP
310
AQRIDSDDAL
320
NHDFFWSDPM
330
PSDLKGMLST
340
HLTSMFEYLA
350
PPRRKGSQIT
360
QQSTNQSRNP
370
ATTNQTEFER
VF
Gene Ontology
| Classification |
GO ID |
Description |
| Biological Process |
GO:0006368 |
transcription elongation by RNA polymerase II |
| Cellular Component |
GO:0000307 |
cyclin-dependent protein kinase holoenzyme complex |
| Cellular Component |
GO:0008024 |
cyclin/CDK positive transcription elongation factor complex |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0016020 |
membrane |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0070691 |
P-TEFb complex |
| Cellular Component |
GO:0016605 |
PML body |
| Cellular Component |
GO:0008023 |
transcription elongation factor complex |
| Molecular Function |
GO:0097322 |
7SK snRNA binding |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0003682 |
chromatin binding |
| Molecular Function |
GO:0004693 |
cyclin-dependent protein serine/threonine kinase activity |
| Molecular Function |
GO:0003677 |
DNA binding |
| Molecular Function |
GO:0140191 |
histone H1-4S187 kinase activity |
| Molecular Function |
GO:0016301 |
kinase activity |
| Molecular Function |
GO:0004672 |
protein kinase activity |
| Molecular Function |
GO:0019901 |
protein kinase binding |
| Molecular Function |
GO:0106310 |
protein serine kinase activity |
| Molecular Function |
GO:0004674 |
protein serine/threonine kinase activity |
| Molecular Function |
GO:0000978 |
RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| Molecular Function |
GO:0008353 |
RNA polymerase II CTD heptapeptide repeat kinase activity |
| Molecular Function |
GO:0001223 |
transcription coactivator binding |
| Molecular Function |
GO:0003711 |
transcription elongation factor activity |
| Biological Process |
GO:0008283 |
cell population proliferation |
| Biological Process |
GO:0071345 |
cellular response to cytokine stimulus |
| Biological Process |
GO:0006281 |
DNA repair |
| Biological Process |
GO:0043923 |
host-mediated activation of viral transcription |
| Biological Process |
GO:0120186 |
negative regulation of protein localization to chromatin |
| Biological Process |
GO:0051647 |
nucleus localization |
| Biological Process |
GO:0120187 |
positive regulation of protein localization to chromatin |
| Biological Process |
GO:0045944 |
positive regulation of transcription by RNA polymerase II |
| Biological Process |
GO:0032968 |
positive regulation of transcription elongation by RNA polymerase II |
| Biological Process |
GO:0006468 |
protein phosphorylation |
| Biological Process |
GO:0051726 |
regulation of cell cycle |
| Biological Process |
GO:0006282 |
regulation of DNA repair |
| Biological Process |
GO:0031440 |
regulation of mRNA 3'-end processing |
| Biological Process |
GO:0051147 |
regulation of muscle cell differentiation |
| Biological Process |
GO:0031297 |
replication fork processing |
| Biological Process |
GO:0006366 |
transcription by RNA polymerase II |
| Biological Process |
GO:0140673 |
transcription elongation-coupled chromatin remodeling |
| Biological Process |
GO:0006367 |
transcription initiation at RNA polymerase II promoter |
Reference
[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.