Names & Taxonomy

Uniprot ID:
P50750
Entry Name:
CDK9_HUMAN
Status:
reviewed
Protein Names:
Cyclin-dependent kinase 9 (EC 2.7.11.22) (EC 2.7.11.23) (C-2K) (Cell division cycle 2-like protein kinase 4) (Cell division protein kinase 9) (Serine/threonine-protein kinase PITALRE) (Tat-associated kinase complex catalytic subunit)
Gene Names:
CDK9 CDC2L4 TAK
Gene Names Primary:
CDK9
Organism:
Homo sapiens (Human)

Structure

Length:
372
Sequence:
MAKQYDSVECPFCDEVSKYEKLAKIGQGTFGEVFKARHRKTGQKVALKKVLMENEKEGFPITALREIKILQLLKHENVVNLIEICRTKASPYNRCKGSIYLVFDFCEHDLAGLLSNVLVKFTLSEIKRVMQMLLNGLYYIHRNKILHRDMKAANVLITRDGVLKLADFGLARAFSLAKNSQPNRYTNRVVTLWYRPPELLLGERDYGPPIDLWGAGCIMAEMWTRSPIMQGNTEQHQLALISQLCGSITPEVWPNVDNYELYEKLELVKGQKRKVKDRLKAYVRDPYALDLIDKLLVLDPAQRIDSDDALNHDFFWSDPMPSDLKGMLSTHLTSMFEYLAPPRRKGSQITQQSTNQSRNPATTNQTEFERVF
Proteomes:
UP000005640

Subcellular location

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.

Function

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.
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.; ATP + = ADP + phosphate.
Enzyme Regulation:
ENZYME REGULATION: Inhibited by CDKI-71, CR8, GPC-286199, AG-024322, flavopiridol (alvocidib), RBG-286147, anilinopyrimidine 32, arylazopyrazole 31b, indirubin 3'-monoxime, meriolin 3,P276-00, olomoucine II, pyrazolotriazine, meriolin, variolin, thiazolyl-pyrimidine, thiazolyl-pyrimidine, indirubin-30-monoxime, ZK 304709, AG-012986, AT7519, R547, RGB-286638, imidazole pyrimidine, EXEL-3700, EXEL-8647, 5,6-dichloro-1-b-ribofur-anosyl-benzimidazole (DRB), P276-00, roscovitine (seliciclib, CYC202) and SNS-032 (BMS-387032). Activation by Thr-186 phosphorylation is calcium Ca(2+) signaling pathway-dependent; actively inactivated by dephosphorylation mediated by PPP1CA, PPM1A and PPM1B. Reversibly repressed by acetylation at Lys-44 and Lys-48.
Active Site:
ACT_SITE 149 149 Proton acceptor.
Gene Ontology Go:
cytoplasm
intracellular membrane-bounded organelle
membrane
nucleoplasm
PML body
positive transcription elongation factor complex b
transcription elongation factor complex
7SK snRNA binding
ATP binding
chromatin binding
cyclin-dependent protein serine/threonine kinase activity
DNA binding
protein kinase activity
RNA polymerase II carboxy-terminal domain kinase activity
RNA polymerase II core promoter sequence-specific DNA binding
transcription coactivator binding
cell proliferation
cellular response to cytokine stimulus
DNA repair
gene expression
negative regulation of cell cycle arrest
negative regulation of mRNA polyadenylation
positive regulation of cardiac muscle hypertrophy
positive regulation of histone H2B ubiquitination
positive regulation of histone phosphorylation
positive regulation of mRNA 3'-UTR binding
positive regulation of transcription from RNA polymerase II promoter
positive regulation of viral transcription
protein phosphorylation
regulation of DNA repair
regulation of histone modification
regulation of muscle cell differentiation
replication fork processing
response to drug
transcription elongation from RNA polymerase II promoter
transcription from RNA polymerase II promoter
transcription initiation from RNA polymerase II promoter
transcription, DNA-templated
transforming growth factor beta receptor signaling pathway
viral process
Gene Ontology Biological Process:
cell proliferation
cellular response to cytokine stimulus
DNA repair
gene expression
negative regulation of cell cycle arrest
negative regulation of mRNA polyadenylation
positive regulation of cardiac muscle hypertrophy
positive regulation of histone H2B ubiquitination
positive regulation of histone phosphorylation
positive regulation of mRNA 3'-UTR binding
positive regulation of transcription from RNA polymerase II promoter
positive regulation of viral transcription
protein phosphorylation
regulation of DNA repair
regulation of histone modification
regulation of muscle cell differentiation
replication fork processing
response to drug
transcription, DNA-templated
transcription elongation from RNA polymerase II promoter
transcription from RNA polymerase II promoter
transcription initiation from RNA polymerase II promoter
transforming growth factor beta receptor signaling pathway
viral process
Gene Ontology Molecular Function:
7SK snRNA binding
ATP binding
chromatin binding
cyclin-dependent protein serine/threonine kinase activity
DNA binding
protein kinase activity
RNA polymerase II carboxy-terminal domain kinase activity
RNA polymerase II core promoter sequence-specific DNA binding
transcription coactivator binding
Gene Ontology Cellular Component:
cytoplasm
intracellular membrane-bounded organelle
membrane
nucleoplasm
PML body
positive transcription elongation factor complex b
transcription elongation factor complex
Keywords:
3D-structure
ATP-binding
Acetylation
Alternative splicing
Complete proteome
Cytoplasm
DNA damage
DNA repair
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transcription
Transcription regulation
Transferase
Ubl conjugation
Interacts With:
Q13535; Q8WXE1; O60563; Q16543; Q9HAW4; Q7L2E3; Q13451; O94992; P07900; P08238; Q6NYC1; Q4G0J3; Q9Y5X4; P04608

Publication

PubMed ID:
8170997 7695608 10903437 15164053 15489334 9491887 9857195 9499409 10393184 10574912 10912001 10757782 10958691 11145967 11112772 11575923 11884399 12065898 12115727 11809800 12037670 12718890 15564463 14701750 15965233 16109376 16109377 17956865 17643375 17452463 18483222 18829461 18249148 18691976 18250157 18362169 19844166 19575011 19369195 20493174 20930849 20081228 20471948 20159561 20980437 21269460 22195968 21406692 21484792 21127351 21448926 21533037 16885020 18728388 19029809 18423896 19238148 19757441 21200140 23029222 24275569 20535204 18566585 20851342 21779453 17344846