Catalytic activity:ATP + a protein = ADP + a phosphoprotein. ,enzyme regulation:Inhibited by wortmannin. Activity of the enzyme seems to be attenuated by autophosphorylation. ,Function:Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA nonhomologous end joining (NHEJ) required for double-strand break (DSB) repair and V (D) J recombination. Must be bound to DNA to express its catalytic properties. Promotes processing of hairpin DNA structures in V (D) J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) . The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step. Required to protect and align broken ends of DNA. May also act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage. Found at the ends of chromosomes , suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. Also involved in modulation of transcription. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX , thereby regulating DNA damage response mechanism. Phosphorylates DCLRE1C , c-Abl/ABL1 , histone H1 , HSPCA , c-jun/JUN , p53/TP53 , PARP1 , POU2F1 , DHX9 , SRF , XRCC1 , XRCC1 , XRCC4 , XRCC5 , XRCC6 , WRN , c-myc/MYC and RFA2. Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA. Ability to phosphorylate TP53/p53 in the presence of supercoiled DNA is dependent on C1D. ,PTM:Phosphorylated upon DNA damage , probably by ATM or ATR. Autophosphorylated on Thr-2609 , Thr-2638 and Thr-2647. Thr-2609 is a DNA damage-inducible phosphorylation site (inducible with ionizing radiation , IR) . Autophosphorylation induces a conformational change that leads to remodeling of the DNA-PK complex , requisite for efficient end processing and DNA repair. ,similarity:Belongs to the PI3/PI4-kinase family. ,similarity:Contains 1 FAT domain. ,similarity:Contains 1 FATC domain. ,similarity:Contains 1 PI3K/PI4K domain. ,similarity:Contains 2 HEAT repeats. ,similarity:Contains 3 TPR repeats. ,subunit:DNA-PK is a heterotrimer of PRKDC and the Ku p70-p86 (XRCC6-XRCC5) dimer. Formation of this complex may be promoted by interaction with ILF3. Associates with the DNA-bound Ku heterodimer , but it can also bind to and be activated by free DNA. Interacts with DNA-PKcs-interacting protein (KIP) with the region upstream the kinase domain. PRKDC alone also interacts with and phosphorylates DCLRE1C , thereby activating the latent endonuclease activity of this protein. Interacts with C1D. ,
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