Version 5.4
Homo sapiens Protein: CDK9
Summary
InnateDB Protein IDBP-381018.5
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 ENSP00000395872
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:0004672 protein kinase activity
GO:0005524 ATP binding
GO:0016772 transferase activity, transferring phosphorus-containing groups
Biological Process
GO:0006468 protein phosphorylation
GO:0045087 innate immune response (InnateDB)
Cellular Component
Protein Structure and Domains
PDB ID
InterPro IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR011009 Protein kinase-like domain
PFAM PF00069
PF07714
PRINTS PR00109
PIRSF
SMART
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt
PhosphoSite PhosphoSite-P50750
TrEMBL X6RE90
UniProt Splice Variant
Entrez Gene 1025
UniGene Hs.706809
RefSeq
HUGO HGNC:1780
OMIM 603251
CCDS
HPRD 16016
IMGT
EMBL AL162586
GenPept

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca