Cyclin-dependent kinase 9

Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb.

CDK9
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3BLH, 3BLQ, 3BLR, 3LQ5, 3MI9, 3MIA, 3MY1, 3TN8, 3TNH, 3TNI, 4BCF, 4BCG, 4BCH, 4BCI, 4BCJ, 4EC8, 4EC9, 4IMY, 4OGR, 4OR5
Identifiers
Aliases	CDK9, C-2k, CDC2L4, CTK1, PITALRE, TAK, cyclin-dependent kinase 9, cyclin dependent kinase 9
External IDs	OMIM: 603251; MGI: 1328368; HomoloGene: 55566; GeneCards: CDK9; OMA:CDK9 - orthologs
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q34.11 Start 127,785,679 bp[1] End 127,790,792 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 B Start 32,595,796 bp[2] End 32,603,088 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right uterine tube left ovary right ovary sural nerve left uterine tube gastric mucosa right hemisphere of cerebellum anterior pituitary body of uterus canal of the cervix Top expressed in granulocyte stroma of bone marrow superior frontal gyrus thymus fetal liver hematopoietic progenitor cell tibiofemoral joint primary visual cortex dermis epiblast spleen More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding transferase activity protein kinase activity 7SK snRNA binding transcription coactivator binding snRNA binding ATP binding RNA polymerase II core promoter sequence-specific DNA binding DNA binding transcription factor binding protein binding protein serine/threonine kinase activity chromatin binding kinase activity cyclin-dependent protein serine/threonine kinase activity RNA polymerase II CTD heptapeptide repeat kinase activity protein kinase binding cyclin binding RNA polymerase II cis-regulatory region sequence-specific DNA binding Cellular component cytoplasm nucleus membrane nucleoplasm transcription elongation factor complex cyclin/CDK positive transcription elongation factor complex PML body chromosome cytoplasmic ribonucleoprotein granule cyclin-dependent protein kinase holoenzyme complex Biological process positive regulation of cardiac muscle hypertrophy positive regulation of mRNA 3'-UTR binding regulation of muscle cell differentiation negative regulation of mRNA polyadenylation DNA repair cellular response to cytokine stimulus positive regulation of viral transcription replication fork processing protein phosphorylation regulation of histone modification regulation of mitotic cell cycle cellular response to DNA damage stimulus transcription initiation from RNA polymerase II promoter regulation of DNA repair regulation of transcription, DNA-templated cell population proliferation transcription by RNA polymerase II phosphorylation positive regulation of histone H2B ubiquitination positive regulation of transcription by RNA polymerase II transcription, DNA-templated snRNA transcription by RNA polymerase II transcription elongation from RNA polymerase II promoter phosphorylation of RNA polymerase II C-terminal domain positive regulation of transcription elongation from RNA polymerase II promoter Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1025 107951 Ensembl ENSG00000136807 ENSMUSG00000009555 UniProt P50750 Q99J95 RefSeq (mRNA) NM_001261 NM_130860 RefSeq (protein) NP_001252 NP_001252.1 NP_570930 Location (UCSC) Chr 9: 127.79 – 127.79 Mb Chr 2: 32.6 – 32.6 Mb PubMed search [3] [4]
Wikidata
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Function

The protein encoded by this gene is a member of the cyclin-dependent 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.^[5]

CDK9 is also known to associate with other proteins such as TRAF2, and be involved in differentiation of skeletal muscle.^[6]

Inhibitors

Based on molecular docking results, Ligands-3, 5, 14, and 16 were screened among 17 different Pyrrolone-fused benzosuberene compounds as potent and specific inhibitors without any cross-reactivity against different CDK isoforms. Analysis of MD simulations and MM-PBSA studies, revealed the binding energy profiles of all the selected complexes. Selected ligands performed better than the experimental drug candidate (Roscovitine). Ligands-5 and 16 show specificity for CDK9. These ligands are expected to possess lower risk of side effects due to their natural origin. ^[7]

Interactions

CDK9 has been shown to interact with:

• Androgen receptor,^[8]
• CDC34^[9] and
• CCNK,^[10]
• CCNT1,^{[10][11][12][13][14][15][9][16][17]}
• CCNT2,^[11]
• MYBL2,^[16]
• RELA,^[18]
• RB1,^[19]
• SKP1A.^[9]
• SUPT5H,^[17] and
• RNAP II.^[20]