Tchem CDK9 Cyclin-dependent kinase 9

Protein Summary

Description

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. 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 Accession IDs

• P50750
• Q5JU24
• Q5JU25
• Q5U006
• Q96TF1

Gene Name

• CDK9

Ensembl ID

• ENST00000373264
• ENSP00000362361
• ENSG00000136807

Symbol

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

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
molecular function	0.99
biological process	0.98
protein complex	0.95
pathway	0.85

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Tyrosine Protein Kinase / Cyclin-dependent Kinase 9

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Cyclin-dependent Kinase 9

DTO Classes

Protein / Kinase / Protein Kinase / Cmgc Group / Cdk Family / Cdk9 Subfamily / Cyclin-dependent Kinase 9

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 595.46   (req: < 5)

Gene RIFs: 120   (req: <= 3)

Antibodies: 503   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 595.46   (req: >= 5)

Gene RIFs: 120   (req: > 3)

Antibodies: 503   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 38

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 282

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (5)

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (1)

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trilaciclib

CDK9Tchem Kinase

INHIBITOR pKd : 9.57

Active Ligands (282)

Explore Active Ligands

1 – 10 of 282

SID103905531

CDK9Tchem Kinase

pKi : 9.5

RGB-286638

CDK9Tchem Kinase

pKd : 8.52

SID103904605

CDK9Tchem Kinase

pKi : 7.7

AT-7519

CDK9Tchem Kinase

pKd : 8.1

SID103904984

CDK9Tchem Kinase

pKi : 9.7

SID103904189

CDK9Tchem Kinase

pKi : 8

SID103904612

CDK9Tchem Kinase

pKi : 8.1

R547

CDK9Tchem Kinase

pKd : 9.27

SID103904604

CDK9Tchem Kinase

pKi : 7.9

SID103904231

CDK9Tchem Kinase

pKi : 8.2

Protein-Protein Interactions (298)

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• See Interactions on String-DB

HEXIM1

Tbio

Novelty:  0.0142443

p_int:  0.999999816

p_ni:  1.84e-7

Score:  0.98

Data Source:  BioPlex,STRINGDB

CCNT1

Tchem

Novelty:  0.00526848

p_int:  0.999999749

p_ni:  2.51e-7

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

HEXIM2

Tbio

Novelty:  0.14814693

p_int:  0.999999569

p_ni:  4.31e-7

Score:  0.953

Data Source:  BioPlex,STRINGDB

HSP90AB3P

Tdark

p_int:  0.999999548

p_ni:  4.52e-7

Data Source:  BioPlex

CCNT2

Tbio

Novelty:  0.04593314

p_int:  0.99999954

p_ni:  4.6e-7

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

HSP90AB4P

Tdark

p_int:  0.999999442

p_ni:  5.58e-7

Data Source:  BioPlex

AFF4

Tbio

Family:  TF

Novelty:  0.02113896

p_int:  0.999999437

p_ni:  5.63e-7

Score:  0.999

Data Source:  BioPlex,STRINGDB

HSP90AA4P

Tdark

p_int:  0.999999258

p_ni:  7.4e-7

p_wrong:  3e-9

Data Source:  BioPlex

AFF1

Tbio

Family:  TF

Novelty:  0.00094358

p_int:  0.999997628

p_ni:  0.000001246

p_wrong:  0.000001126

Score:  0.875

Data Source:  BioPlex,STRINGDB

FKBP5

Tchem

Family:  Enzyme

Novelty:  0.00214511

p_int:  0.999990428

p_ni:  0.000009572

Score:  0.416

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (60)

Reactome (33)

KEGG (1)

PathwayCommons (8)

WikiPathways (18)

Disease (R-HSA-1643685)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	ESR-mediated signaling	189 targets	R-HSA-8939211
Reactome	Estrogen-dependent gene expression	119 targets	R-HSA-9018519
Reactome	Formation of HIV elongation complex in the absence of HIV Tat	48 targets	R-HSA-167152
Reactome	Formation of HIV-1 elongation complex containing HIV-1 Tat	47 targets	R-HSA-167200

Name	Explore in Pharos	Explore in Source
Disease	1105 targets	R-HSA-1643685
ESR-mediated signaling	189 targets	R-HSA-8939211
Estrogen-dependent gene expression	119 targets	R-HSA-9018519
Formation of HIV elongation complex in the absence of HIV Tat	48 targets	R-HSA-167152
Formation of HIV-1 elongation complex containing HIV-1 Tat	47 targets	R-HSA-167200

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (48)

Functions (15)

Components (10)

Processes (23)

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GO Term	Evidence	Assigned by
7SK snRNA binding	Inferred from Direct Assay (IDA)	UniProtKB
cyclin-dependent protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
DNA binding	Inferred from Direct Assay (IDA)	MGI
RNA polymerase II CTD heptapeptide repeat kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
transcription coactivator binding	Inferred from Physical Interaction (IPI)	UniProtKB
cyclin binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
transcription factor binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
transcription regulatory region DNA binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
chromatin binding	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
kinase activity	Traceable Author Statement (TAS)	Reactome

Disease Associations (null)

No disease associations found

GWAS Traits (8)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
hemoglobin measurement	EFO_0004509	4	3	4		85.4
hematocrit	EFO_0004348	4	2	4		77.1
erythrocyte count	EFO_0004305	2	2	2		67.1
monocyte percentage of leukocytes	EFO_0007989	2	2	2		63.4
neutrophil percentage of leukocytes	EFO_0007990	1	1	1		44

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
hemoglobin measurement	EFO_0004509	4		85.4
hematocrit	EFO_0004348	4		77.1
erythrocyte count	EFO_0004305	2		67.1
monocyte percentage of leukocytes	EFO_0007989	2		63.4
neutrophil percentage of leukocytes	EFO_0007990	1		44

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UniProt Keyword Find Similar Targets

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3D-structure
Acetylation
Alternative splicing
ATP-binding
Complete proteome
Cytoplasm
DNA damage
DNA repair
Kinase
Nucleotide-binding

GWAS Trait Find Similar Targets

No Header	No Header
basophil percentage of leukocytes
erythrocyte count
granulocyte percentage of myeloid white cells
hematocrit
hemoglobin measurement
monocyte percentage of leukocytes
neutrophil percentage of leukocytes
red blood cell density measurement

MGI Phenotype Find Similar Targets

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behavior/neurological phenotype
cardiovascular system phenotype
homeostasis/metabolism phenotype
integument phenotype
mortality/aging
reproductive system phenotype

IDG Resources

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Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cyclin dependent kinase 9	VGNC:8807	464755
Mouse	cyclin-dependent kinase 9 (CDC2-related kinase)	MGI:1328368	107951
Rat	cyclin-dependent kinase 9	RGD:1359638	362110
Dog	cyclin dependent kinase 9	VGNC:39062	100855805
Horse	cyclin dependent kinase 9	VGNC:16357	100070437

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cyclin dependent kinase 9
Mouse	cyclin-dependent kinase 9 (CDC2-related kinase)
Rat	cyclin-dependent kinase 9
Dog	cyclin dependent kinase 9
Horse	cyclin dependent kinase 9

Publication Statistics

PubMed Score 595.46

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PubTator Score 428.30

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Text Mined References (257)

GeneRif Annotations (120)

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PMID	Year	Title