TISIDB

Summary
Symbol	CDK9
Name	cyclin-dependent kinase 9
Aliases	PITALRE; C-2k; TAK; CDC2L4; cyclin-dependent kinase 9 (CDC2-related kinase); CTK1; cell division cycle 2-lik ......
Chromosomal Location	9q34.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	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.
Domain	PF00069 Protein kinase domain
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.

> Gene Ontology [ TOP ]
Biological Process	GO:0003012 muscle system process GO:0003300 cardiac muscle hypertrophy GO:0006260 DNA replication GO:0006261 DNA-dependent DNA replication GO:0006282 regulation of DNA repair GO:0006352 DNA-templated transcription, initiation GO:0006354 DNA-templated transcription, elongation GO:0006367 transcription initiation from RNA polymerase II promoter GO:0006368 transcription elongation from RNA polymerase II promoter GO:0006378 mRNA polyadenylation GO:0006397 mRNA processing GO:0007050 cell cycle arrest GO:0009301 snRNA transcription GO:0010611 regulation of cardiac muscle hypertrophy GO:0010613 positive regulation of cardiac muscle hypertrophy GO:0010948 negative regulation of cell cycle process GO:0014742 positive regulation of muscle hypertrophy GO:0014743 regulation of muscle hypertrophy GO:0014896 muscle hypertrophy GO:0014897 striated muscle hypertrophy GO:0016073 snRNA metabolic process GO:0016570 histone modification GO:0016572 histone phosphorylation GO:0016574 histone ubiquitination GO:0019058 viral life cycle GO:0019080 viral gene expression GO:0019083 viral transcription GO:0031056 regulation of histone modification GO:0031058 positive regulation of histone modification GO:0031123 RNA 3'-end processing GO:0031124 mRNA 3'-end processing GO:0031297 replication fork processing GO:0031396 regulation of protein ubiquitination GO:0031398 positive regulation of protein ubiquitination GO:0031440 regulation of mRNA 3'-end processing GO:0031441 negative regulation of mRNA 3'-end processing GO:0033127 regulation of histone phosphorylation GO:0033129 positive regulation of histone phosphorylation GO:0033182 regulation of histone ubiquitination GO:0033184 positive regulation of histone ubiquitination GO:0033523 histone H2B ubiquitination GO:0042493 response to drug GO:0042692 muscle cell differentiation GO:0042795 snRNA transcription from RNA polymerase II promoter GO:0043500 muscle adaptation GO:0043502 regulation of muscle adaptation GO:0043631 RNA polyadenylation GO:0043900 regulation of multi-organism process GO:0043902 positive regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0044033 multi-organism metabolic process GO:0044057 regulation of system process GO:0045005 DNA-dependent DNA replication maintenance of fidelity GO:0045786 negative regulation of cell cycle GO:0045787 positive regulation of cell cycle GO:0046782 regulation of viral transcription GO:0048524 positive regulation of viral process GO:0050434 positive regulation of viral transcription GO:0050684 regulation of mRNA processing GO:0050686 negative regulation of mRNA processing GO:0050792 regulation of viral process GO:0051052 regulation of DNA metabolic process GO:0051098 regulation of binding GO:0051099 positive regulation of binding GO:0051147 regulation of muscle cell differentiation GO:0071156 regulation of cell cycle arrest GO:0071157 negative regulation of cell cycle arrest GO:0090257 regulation of muscle system process GO:0098781 ncRNA transcription GO:1900363 regulation of mRNA polyadenylation GO:1900364 negative regulation of mRNA polyadenylation GO:1902275 regulation of chromatin organization GO:1902415 regulation of mRNA binding GO:1902416 positive regulation of mRNA binding GO:1903311 regulation of mRNA metabolic process GO:1903312 negative regulation of mRNA metabolic process GO:1903320 regulation of protein modification by small protein conjugation or removal GO:1903322 positive regulation of protein modification by small protein conjugation or removal GO:1903837 regulation of mRNA 3'-UTR binding GO:1903839 positive regulation of mRNA 3'-UTR binding GO:1903900 regulation of viral life cycle GO:1903902 positive regulation of viral life cycle GO:1905214 regulation of RNA binding GO:1905216 positive regulation of RNA binding GO:1905269 positive regulation of chromatin organization GO:2001020 regulation of response to DNA damage stimulus GO:2001166 regulation of histone H2B ubiquitination GO:2001168 positive regulation of histone H2B ubiquitination
Molecular Function	GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding GO:0001046 core promoter sequence-specific DNA binding GO:0001047 core promoter binding GO:0001221 transcription cofactor binding GO:0001223 transcription coactivator binding GO:0003682 chromatin binding GO:0004674 protein serine/threonine kinase activity GO:0004693 cyclin-dependent protein serine/threonine kinase activity GO:0008134 transcription factor binding GO:0008353 RNA polymerase II carboxy-terminal domain kinase activity GO:0017069 snRNA binding GO:0097322 7SK snRNA binding GO:0097472 cyclin-dependent protein kinase activity
Cellular Component	GO:0000307 cyclin-dependent protein kinase holoenzyme complex GO:0008023 transcription elongation factor complex GO:0008024 cyclin/CDK positive transcription elongation factor complex GO:0016604 nuclear body GO:0016605 PML body GO:0019908 nuclear cyclin-dependent protein kinase holoenzyme complex GO:0032806 carboxy-terminal domain protein kinase complex GO:0061695 transferase complex, transferring phosphorus-containing groups GO:1902554 serine/threonine protein kinase complex GO:1902911 protein kinase complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-1643685: Disease R-HSA-112387: Elongation arrest and recovery R-HSA-167152: Formation of HIV elongation complex in the absence of HIV Tat R-HSA-167200: Formation of HIV-1 elongation complex containing HIV-1 Tat R-HSA-112382: Formation of RNA Pol II elongation complex R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-162906: HIV Infection R-HSA-162587: HIV Life Cycle R-HSA-167169: HIV Transcription Elongation R-HSA-167287: HIV elongation arrest and recovery R-HSA-162909: Host Interactions of HIV factors R-HSA-5663205: Infectious disease R-HSA-176034: Interactions of Tat with host cellular proteins R-HSA-162599: Late Phase of HIV Life Cycle R-HSA-167290: Pausing and recovery of HIV elongation R-HSA-167238: Pausing and recovery of Tat-mediated HIV elongation R-HSA-674695: RNA Polymerase II Pre-transcription Events R-HSA-73857: RNA Polymerase II Transcription R-HSA-75955: RNA Polymerase II Transcription Elongation R-HSA-6807505: RNA polymerase II transcribes snRNA genes R-HSA-2173796: SMAD2/SMAD3 R-HSA-162582: Signal Transduction R-HSA-170834: Signaling by TGF-beta Receptor Complex R-HSA-6796648: TP53 Regulates Transcription of DNA Repair Genes R-HSA-167243: Tat-mediated HIV elongation arrest and recovery R-HSA-167246: Tat-mediated elongation of the HIV-1 transcript R-HSA-167172: Transcription of the HIV genome R-HSA-3700989: Transcriptional Regulation by TP53 R-HSA-2173793: Transcriptional activity of SMAD2/SMAD3

> KEGG and Reactome Pathway

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KEGG

Reactome

R-HSA-1643685: Disease
R-HSA-112387: Elongation arrest and recovery
R-HSA-167152: Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167200: Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-112382: Formation of RNA Pol II elongation complex
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-162906: HIV Infection
R-HSA-162587: HIV Life Cycle
R-HSA-167169: HIV Transcription Elongation
R-HSA-167287: HIV elongation arrest and recovery
R-HSA-162909: Host Interactions of HIV factors
R-HSA-5663205: Infectious disease
R-HSA-176034: Interactions of Tat with host cellular proteins
R-HSA-162599: Late Phase of HIV Life Cycle
R-HSA-167290: Pausing and recovery of HIV elongation
R-HSA-167238: Pausing and recovery of Tat-mediated HIV elongation
R-HSA-674695: RNA Polymerase II Pre-transcription Events
R-HSA-73857: RNA Polymerase II Transcription
R-HSA-75955: RNA Polymerase II Transcription Elongation
R-HSA-6807505: RNA polymerase II transcribes snRNA genes
R-HSA-2173796: SMAD2/SMAD3
R-HSA-162582: Signal Transduction
R-HSA-170834: Signaling by TGF-beta Receptor Complex
R-HSA-6796648: TP53 Regulates Transcription of DNA Repair Genes
R-HSA-167243: Tat-mediated HIV elongation arrest and recovery
R-HSA-167246: Tat-mediated elongation of the HIV-1 transcript
R-HSA-167172: Transcription of the HIV genome
R-HSA-3700989: Transcriptional Regulation by TP53
R-HSA-2173793: Transcriptional activity of SMAD2/SMAD3

Summary
Symbol	CDK9
Name	cyclin-dependent kinase 9
Aliases	PITALRE; C-2k; TAK; CDC2L4; cyclin-dependent kinase 9 (CDC2-related kinase); CTK1; cell division cycle 2-lik ......
Chromosomal Location	9q34.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CDK9 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
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Summary
Symbol	CDK9
Name	cyclin-dependent kinase 9
Aliases	PITALRE; C-2k; TAK; CDC2L4; cyclin-dependent kinase 9 (CDC2-related kinase); CTK1; cell division cycle 2-lik ......
Chromosomal Location	9q34.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of CDK9 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	CDK9
Name	cyclin-dependent kinase 9
Aliases	PITALRE; C-2k; TAK; CDC2L4; cyclin-dependent kinase 9 (CDC2-related kinase); CTK1; cell division cycle 2-lik ......
Chromosomal Location	9q34.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of CDK9 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.045	0.81
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.194	0.924
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.064	0.966
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.234	0.452
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.093	0.961
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.421	0.874
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.216	0.537
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.297	0.832
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.116	0.941
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.105	0.945
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.485	0.829
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.053	0.307

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CDK9 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	CDK9
Name	cyclin-dependent kinase 9
Aliases	PITALRE; C-2k; TAK; CDC2L4; cyclin-dependent kinase 9 (CDC2-related kinase); CTK1; cell division cycle 2-lik ......
Chromosomal Location	9q34.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CDK9. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	CDK9
Name	cyclin-dependent kinase 9
Aliases	PITALRE; C-2k; TAK; CDC2L4; cyclin-dependent kinase 9 (CDC2-related kinase); CTK1; cell division cycle 2-lik ......
Chromosomal Location	9q34.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CDK9. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CDK9. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CDK9
Name	cyclin-dependent kinase 9
Aliases	PITALRE; C-2k; TAK; CDC2L4; cyclin-dependent kinase 9 (CDC2-related kinase); CTK1; cell division cycle 2-lik ......
Chromosomal Location	9q34.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CDK9. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	CDK9
Name	cyclin-dependent kinase 9
Aliases	PITALRE; C-2k; TAK; CDC2L4; cyclin-dependent kinase 9 (CDC2-related kinase); CTK1; cell division cycle 2-lik ......
Chromosomal Location	9q34.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CDK9 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CDK9
Name	cyclin-dependent kinase 9
Aliases	PITALRE; C-2k; TAK; CDC2L4; cyclin-dependent kinase 9 (CDC2-related kinase); CTK1; cell division cycle 2-lik ......
Chromosomal Location	9q34.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CDK9 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CDK9
Name	cyclin-dependent kinase 9
Aliases	PITALRE; C-2k; TAK; CDC2L4; cyclin-dependent kinase 9 (CDC2-related kinase); CTK1; cell division cycle 2-lik ......
Chromosomal Location	9q34.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CDK9 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CDK9.

ID	Name	Drug Type	Targets	#Targets
DB03496	Alvocidib	Small Molecule	CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, EGFR, PYGB, PYGL, ......	12
DB06195	Seliciclib	Small Molecule	CDK1, CDK2, CDK7, CDK9, CSNK1E, MAPK1, MAPK3	7

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