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FLASH GENE
Symbol CDK9 contributors: mct - updated : 28-12-2015
HGNC name cyclin-dependent kinase 9
HGNC id 1780
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinecolon highly
 pharynx   highly
Endocrinethyroid   highly
Reproductivefemale systemuteruscervix highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • eleven conserved regions characteristic of the protein kinase catalytic domain
  • a putative ATP binding site
  • a nuclear localization signal (NLS)
  • a PSTAIRE motif (PITALRE)
  • mono polymer heteromer , dimer , polymer , complex
    HOMOLOGY
    interspecies homolog to yeast S.cerevisiae cdc28
    intraspecies homolog to cyclin dependent kinase (CDC2) protein kinase 2
    Homologene
    FAMILY
  • protein kinase superfamily
  • CMGC Ser/Thr protein kinase family
  • CDC2/CDKX subfamily
  • CATEGORY enzyme , regulatory , RNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    text
  • accumulates on chromatin in response to replication stress and limits the amount of single-stranded DNA in cells under stress
  • basic FUNCTION
  • serine/threonine kinase, phosphorylating the largest subunit of RNA polymerase II, involved in cardiac hypertrophy
  • multimeric protein complex, TAK/P-TEFb which is a positive elongation factor for RNA polymerase II directed transcription, only via RNA
  • active role for the CDK9/CCNT1 complex during lymphoid differentiation through germinal center reaction
  • is recruited by BRD4 to phosphorylate RNA Pol II and facilitate the transcription of NF-KappaB-dependent inflammatory genes
  • direct role for CDK9–CCNK in checkpoint pathways that maintain genome integrity in response to replication stress
  • regulates AR promoter selectivity and cell growth through serine 81 phosphorylation
  • BRD4 is a CTD Ser2 kinase that is distinct from CDK9 in its substrate specificity
  • CELLULAR PROCESS cell life, proliferation/growth
    nucleotide, transcription, elongation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • catalytic subunit of a general RNA polymerase 2, transcription elongation factor
  • heterodimer of cyclin-dependent kinase 9 (Cdk9), and one of four cyclin partners, cyclin T1, T2a, T2b or K
  • component of the replication stress response
  • CDK9–CCNK complex has different biological activities to the CDK9–CCNT1 complex
  • INTERACTION
    DNA binding when tethered to cyclin T or cyclin K
    RNA
    small molecule
    protein
  • phosphorylating HTATSF1 (hSpt5) for interaction with PIN1
  • CCNT (PTEFB activation involved in cardiac muscle-cell hypertrophy)
  • RB protein
  • CCNT1
  • interacting with HIV Tat, suggesting a possible involvement in AIDS
  • CDK9 and CCNK interact with ataxia telangiectasia and Rad3-related protein and other checkpoint signalling proteins
  • CDK9 binds to cyclin K and direct role of CDK9-CCNK in pathways that maintain genome integrity in response to replication stress appear to be evolutionarily conserved
  • AIRE requires CDK9 to activate transcription elongation and co-transcriptional processing of target genes
  • TAF7 interacts with and regulates the enzymatic activities of other transcription factors, including CDK9, GTF2H1, and CIITA, ensuring an orderly progression in transcription initiation
  • CDK9 the kinase of CCNT1 stimulates transcription elongation by phosphorylating POLR2A and transcription elongation factors
  • CDK7 thus acts through GTF2E1, GTF2E2 and SUPT5H to establish, and through CDK9 to relieve, barriers to elongation
  • BCL11B is a major modulator of CDK9 activity, and controls CDK9 function in physiological and pathological conditions
  • interactions of both JMJD6 and BRD4 with the CDK9 complex permit its activation and pause release of regulated coding genes
  • CDK9 is required for the transition from initiation to elongation of transcription, and its AIRE interaction ensures proper expression of AIRE-responsive tissue-specific antigens in the thymus
  • HEXIM1 binds to the CDK9 catalytic site to inhibit CCNT1
  • cell & other
  • HIV
  • REGULATION
    Other regulated by CCNT1,CCNK
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    in apoptotic cardiomyopathy
    constitutional       loss of function
    causes an increase in spontaneous levels of DNA damage signalling in replicating cells and a decreased ability to recover from a transient replication arrest
    Susceptibility to apoptotic cardiomyopathy (by cardiomyocyte enlargement but also defective mitochondrial function)
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS