FEATURES

FAMILY

DESCRIPTION

Also known as CDK9_HUMAN, CDK9, CDC2L4, TAK. Protein kinase involved in the regulation of transcription (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094). 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 (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094). This complex is inactive when in the 7SK snRNP complex form (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094). Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR and the negative elongation factors DSIF and NELF (PubMed:9857195, PubMed:10912001, PubMed:11112772, PubMed:12037670, PubMed:20081228, PubMed:20980437, PubMed:21127351). 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) (PubMed:17956865, PubMed:18362169). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis (PubMed:10393184, PubMed:11112772). P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export (PubMed:15564463, PubMed:19575011, PubMed:19844166). 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 (PubMed:15564463, PubMed:19575011, PubMed:19844166). 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 (PubMed:21127351). 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 (PubMed:20493174). In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6 (PubMed:20493174). Promotes cardiac myocyte enlargement (PubMed:20081228). RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription (PubMed:21127351). AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect (PubMed:9857195, PubMed:10912001, PubMed:11112772). The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation (PubMed:12037670). Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Associates with CCNT1/cyclin-T1, CCNT2/cyclin-T2 (isoform A and isoform B) or CCNK/cyclin-K to form active P-TEFb. P-TEFb forms a complex with AFF4/AF5Q31 and is part of the super elongation complex (SEC). Component of a complex which is composed of at least 5 members: HTATSF1/Tat-SF1, P-TEFb complex, RNA pol II, SUPT5H and NCL/nucleolin. Associates with UBR5 and forms a transcription regulatory complex composed of CDK9, RNAP II, UBR5 and TFIIS/TCEA1 that can stimulate target gene transcription (e.g. gamma fibrinogen/FGG) by recruiting their promoters. Component of the 7SK snRNP inactive complex which is composed of at least 8 members: P-TEFb (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2, LARP7, BCDIN3, SART3 proteins and 7SK and U6 snRNAs. This inactive 7SK snRNP complex can also interact with NCOR1 and HDAC3, probably to regulate CDK9 acetylation. Release of P-TEFb from P-TEFb/7SK snRNP complex requires both PP2B to transduce calcium Ca(2+) signaling in response to stimuli (e.g. UV or hexamethylene bisacetamide (HMBA)) and PPP1CA to dephosphorylate Thr-186. This released P-TEFb remains inactive in the pre-initiation complex with BRD4 until new Thr-186 phosphorylation occurs after the synthesis of a short RNA (PubMed:10393184, PubMed:10574912, PubMed:12037670, PubMed:11884399, PubMed:12065898, PubMed:12718890, PubMed:15965233, PubMed:16109376, PubMed:17452463, PubMed:17643375, PubMed:18249148, PubMed:18483222, PubMed:18566585, PubMed:20159561, PubMed:20471948, PubMed:21127351, PubMed:21779453, PubMed:22195968, PubMed:9491887). Interacts with BRD4; to target chromatin binding (PubMed:16109376, PubMed:16109377, PubMed:18483222). Interacts with JMJD6 (PubMed:24360279). Interacts with activated nuclear STAT3 and RELA/p65 (PubMed:17956865, PubMed:18362169). Binds to AR and MYOD1 (PubMed:12037670, PubMed:20980437). Forms a complex composed of CDK9, CCNT1/cyclin-T1, EP300 and GATA4 that stimulates hypertrophy in cardiomyocytes (PubMed:20081228). The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (By similarity). Interacts with HSF1 (PubMed:27189267). Interacts with TBX21 (By similarity). Isoform 3: binds to KU70/XRCC6 (PubMed:20535204). Interacts with WDR43 (By similarity).

Also known as CDK9_HUMAN, CDK9, CDC2L4, TAK. Protein kinase involved in the regulation of transcription (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, Pu ...

EXTERNAL LINKS

CDK9

Cyclin-dependent kinase 9

CDK9

Molecular Synopsis