CDK9

Gene Information

Official Symbol: CDK9
Official Name: cyclin dependent kinase 9
Aliases and Previous Symbols: N/A
Entrez ID: 1025
UniProt: P50750
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and known as important cell cycle regulators. This kinase was found to be a component of the multiprotein complex TAK/P-TEFb, which is an elongation factor for RNA polymerase II-directed transcription and functions by phosphorylating the C-terminal domain of the largest subunit of RNA polymerase II. This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found to interact with this protein and cyclin T, which suggested a possible involvement of this protein in AIDS. [provided by RefSeq, Jul 2008].
UniProt Summary: 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:0000269|PubMed:10393184, ECO:0000269|PubMed:10574912, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11145967, ECO:0000269|PubMed:11575923, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:11884399, ECO:0000269|PubMed:12037670, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15564463, ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:17956865, ECO:0000269|PubMed:18362169, ECO:0000269|PubMed:19575011, ECO:0000269|PubMed:19844166, ECO:0000269|PubMed:20081228, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:20930849, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:9857195}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Global Fraction of Cell Lines Where Essential: 699/726

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	1/1
909776.0	1/1
bile duct	27/28
blood	28/28
bone	24/25
breast	33/33
central nervous system	55/56
cervix	4/4
colorectal	16/17
esophagus	10/13
fibroblast	1/1
gastric	14/15
kidney	20/21
liver	20/20
lung	72/75
lymphocyte	13/14
ovary	25/26
pancreas	24/24
peripheral nervous system	15/16
plasma cell	15/15
prostate	1/1
skin	24/24
soft tissue	6/7
thyroid	2/2
upper aerodigestive	19/22
urinary tract	29/29
uterus	5/5

Essentiality in NALM6

Essentiality Rank: 503
Expression level (log2 read counts): 6.45

Expression Distribution

Screen	Score
Pyronaridine 1μM R06 exp295	-1.71
GSK461364A 0.005μM R03 exp125	1.73

Gene	Correlation
PRPF8	0.434
HGC6.3	0.422
ATP6V1B2	0.414
POLR2J3	0.41
TBC1D3	0.406
TBC1D3H	0.4

Pkinase Tyr
Pkinase

positive regulation of mRNA 3-UTR binding
regulation of mRNA 3-UTR binding
positive regulation of histone H2B ubiquitination
positive regulation of histone ubiquitination
regulation of histone H2B ubiquitination
positive regulation of mRNA binding
phosphorylation of RNA polymerase II C-terminal domain
7SK snRNA binding
positive regulation of histone phosphorylation
cyclin/CDK positive transcription elongation factor complex
positive regulation of RNA binding
negative regulation of mRNA polyadenylation
regulation of mRNA binding
negative regulation of mRNA 3-end processing
regulation of histone ubiquitination
regulation of RNA binding
regulation of histone phosphorylation
RNA polymerase II CTD heptapeptide repeat kinase activity
positive regulation of transcription elongation from RNA polymerase II promoter
regulation of mRNA polyadenylation
transcription coactivator binding
negative regulation of cell cycle arrest
transcription elongation factor complex
negative regulation of mRNA processing
regulation of mRNA 3-end processing
cyclin-dependent protein serine/threonine kinase activity
cyclin-dependent protein kinase holoenzyme complex
regulation of transcription elongation from RNA polymerase II promoter
cyclin binding
positive regulation of cardiac muscle hypertrophy
positive regulation of DNA-templated transcription, elongation
positive regulation of muscle hypertrophy
replication fork processing
DNA-dependent DNA replication maintenance of fidelity
positive regulation of viral transcription
regulation of DNA-templated transcription, elongation
regulation of cardiac muscle hypertrophy
regulation of muscle hypertrophy
regulation of viral transcription
cytoplasmic ribonucleoprotein granule