======= CDK9 =======
== Gene Information ==
* **Official Symbol**: CDK9
* **Official Name**: cyclin dependent kinase 9
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1025|1025]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P50750|P50750]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=CDK9&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CDK9|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/603251|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}.
|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|
|snRNA transcription by RNA polymerase II|
|snRNA transcription|
|transcription elongation from RNA polymerase II promoter|
|negative regulation of mRNA metabolic process|
|kinase activity|
|regulation of muscle adaptation|
|positive regulation of histone modification|
|DNA-templated transcription, elongation|
|ncRNA transcription|
|PML body|
|positive regulation of chromatin organization|
|regulation of cell cycle arrest|
|positive regulation of viral process|
|positive regulation of protein ubiquitination|
|DNA-dependent DNA replication|
|chromosome|
|regulation of DNA repair|
|positive regulation of protein modification by small protein conjugation or removal|
|regulation of mRNA processing|
|regulation of histone modification|
|regulation of muscle cell differentiation|
|positive regulation of chromosome organization|
|transcription initiation from RNA polymerase II promoter|
|positive regulation of binding|
|regulation of chromatin organization|
|regulation of protein ubiquitination|
|regulation of viral process|
|DNA replication|
|DNA-templated transcription, initiation|
|regulation of response to DNA damage stimulus|
|transcription regulatory region DNA binding|
|regulation of symbiosis, encompassing mutualism through parasitism|
|regulation of protein modification by small protein conjugation or removal|
|regulation of muscle system process|
|nuclear chromatin|
|protein kinase activity|
|negative regulation of cell cycle process|
|regulation of mRNA metabolic process|
|transcription factor binding|
|regulation of chromosome organization|
|regulation of DNA metabolic process|
|protein serine/threonine kinase activity|
|positive regulation of cell cycle|
|regulation of binding|
|chromatin binding|
|protein kinase binding|
|transcription by RNA polymerase II|
|RNA polymerase II proximal promoter sequence-specific DNA binding|
|positive regulation of multi-organism process|
|DNA repair|
|cell population proliferation|
|negative regulation of cell cycle|
|regulation of system process|
|positive regulation of organelle organization|
|regulation of mitotic cell cycle|
|transcription, DNA-templated|
|nucleic acid-templated transcription|
|RNA biosynthetic process|
|regulation of cellular response to stress|
|DNA metabolic process|
|regulation of cell cycle process|
|regulation of multi-organism process|
|cellular response to DNA damage stimulus|
|protein phosphorylation|
|cellular response to cytokine stimulus|
|positive regulation of protein phosphorylation|
|response to drug|
|positive regulation of phosphorylation|
|nucleobase-containing compound biosynthetic process|
|response to cytokine|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|regulation of cell cycle|
|positive regulation of cellular component organization|
|positive regulation of transcription by RNA polymerase II|
|positive regulation of protein modification process|
|phosphorylation|
|regulation of organelle organization|
|organic cyclic compound biosynthetic process|
|negative regulation of RNA metabolic process|
|negative regulation of nucleobase-containing compound metabolic process|
|regulation of protein phosphorylation|
|DNA binding|
|regulation of response to stress|
|ATP binding|
|positive regulation of transcription, DNA-templated|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|cellular nitrogen compound biosynthetic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|RNA metabolic process|
|cellular response to stress|
|positive regulation of protein metabolic process|
|cellular macromolecule biosynthetic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|macromolecule biosynthetic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|regulation of protein modification process|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|membrane|
|gene expression|
|positive regulation of biosynthetic process|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp295|Pyronaridine 1μM R06 exp295]]|-1.71|
|[[:results:exp125|GSK461364A 0.005μM R03 exp125]]|1.73|
^Gene^Correlation^
|[[:human genes:p:prpf8|PRPF8]]|0.434|
|[[:human genes:h:hgc6.3|HGC6.3]]|0.422|
|[[:human genes:a:atp6v1b2|ATP6V1B2]]|0.414|
|[[:human genes:p:polr2j3|POLR2J3]]|0.41|
|[[:human genes:t:tbc1d3|TBC1D3]]|0.406|
|[[:human genes:t:tbc1d3h|TBC1D3H]]|0.4|
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
{{:chemogenomics:nalm6 dist.png?nolink |}}