InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CDK9

Summary

InnateDB Protein

IDBP-86441.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CDK9

Protein Name

cyclin-dependent kinase 9

Synonyms

C-2k; CDC2L4; CTK1; PITALRE; TAK;

Species

Homo sapiens

Ensembl Protein

ENSP00000362361

InnateDB Gene

IDBG-86437 (CDK9)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10393184, ECO:0000269PubMed:10574912, ECO:0000269PubMed:10757782, ECO:0000269PubMed:10912001, ECO:0000269PubMed:11112772, ECO:0000269PubMed:11145967, ECO:0000269PubMed:11575923, ECO:0000269PubMed:11809800, ECO:0000269PubMed:11884399, ECO:0000269PubMed:12037670, ECO:0000269PubMed:14701750, ECO:0000269PubMed:15564463, ECO:0000269PubMed:16109376, ECO:0000269PubMed:16109377, ECO:0000269PubMed:17956865, ECO:0000269PubMed:18362169, ECO:0000269PubMed:19575011, ECO:0000269PubMed:19844166, ECO:0000269PubMed:20081228, ECO:0000269PubMed:20493174, ECO:0000269PubMed:20930849, ECO:0000269PubMed:20980437, ECO:0000269PubMed:21127351, ECO:0000269PubMed:9857195}.

Subcellular Localization

Nucleus. Cytoplasm. Nucleus, PML body. Note=Accumulates on chromatin in response to replication stress. Complexed with CCNT1 in nuclear speckles, but uncomplexed form in the cytoplasm. The translocation from nucleus to cytoplasm is XPO1/CRM1-dependent. Associates with PML body when acetylated.

Disease Associations

Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.

Tissue Specificity

Ubiquitous.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 248 experimentally validated interaction(s) in this database.
They are also associated with 9 interaction(s) predicted by orthology.

Experimentally validated
Total	248 [view]
Protein-Protein	231 [view]
Protein-DNA	12 [view]
Protein-RNA	2 [view]
DNA-DNA	3 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	9 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0004672	protein kinase activity
GO:0004693	cyclin-dependent protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008353	RNA polymerase II carboxy-terminal domain kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0017069	snRNA binding
GO:0044212	transcription regulatory region DNA binding

Biological Process

GO:0006281	DNA repair
GO:0006282	regulation of DNA repair
GO:0006351	transcription, DNA-templated
GO:0006366	transcription from RNA polymerase II promoter
GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0006368	transcription elongation from RNA polymerase II promoter
GO:0006468	protein phosphorylation
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0008283	cell proliferation
GO:0010467	gene expression
GO:0016032	viral process
GO:0031056	regulation of histone modification
GO:0043111	replication fork arrest
GO:0045087	innate immune response (InnateDB)
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0050434	positive regulation of viral transcription
GO:0071157	negative regulation of cell cycle arrest
GO:0071345	cellular response to cytokine stimulus

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0008023	transcription elongation factor complex
GO:0008024	positive transcription elongation factor complex b
GO:0016020	membrane
GO:0016605	PML body
GO:0043231	intracellular membrane-bounded organelle

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt