lmmol · Proteins

Cyclin-dependent kinase 9

UniProt P50750 Organism Homo sapiens Gene CDC2L4, CDK9, TAK EC 2.7.11.22, 2.7.11.23

Also known as: CDC2L4, CDK9, TAK

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 NELFE. 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. Also catalyzes phosphorylation of histone H1.4 (H1-4) at Ser-187' (H1.4S187Ph), a modification associated with transcription activation. 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. Catalyzes phosphorylation of KAT5, promoting KAT5 recruitment to chromatin and histone acetyltransferase activity.

Classification

Family (Pfam)
PF00069 Pkinase
InterPro
CDK, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
Functional cluster
Serine/Threonine Protein Kinases

Experimental structures · PDB · 28

A predicted model is available from AlphaFold.

Gene Ontology · 43

Drugs targeting this protein · 11

Neighborhood · nearest proteins

CDC2L4CDK9Cdk9Cdk9SPT5CCNT1ICP22
Nearest neighbours of Cyclin-dependent kinase 9: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 77 cited papers

A document in the lmmol reference corpus — open public data (UniProt, GO, PDB, the literature graph) rendered as a single cross-linked page. Hover any link to preview its target.