Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA non-homologous 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, FH, SRF, XRCC1, XRCC1, XRCC4, XRCC5, XRCC6, WRN, 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 p53/TP53 in the presence of supercoiled DNA is dependent on C1D. Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway. Belongs to the PI3/PI4-kinase family. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: ATYPICAL group; DNA repair, damage; DNAPK subfamily; EC 22.214.171.124; Kinase, protein; Nucleolus; PIKK family; Protein kinase, Ser/Thr (non-receptor); Protein kinase, atypical
Molecular Function: ATP binding; DNA binding; DNA-dependent protein kinase activity; double-stranded DNA binding; enzyme binding; kinase activity; nucleotide binding; protein binding; protein domain specific binding; protein kinase activity; protein serine/threonine kinase activity; transcription factor binding; transferase activity
Biological Process: activation of innate immune response; B cell lineage commitment; brain development; cellular response to DNA damage stimulus; cellular response to insulin stimulus; DNA repair; double-strand break repair; double-strand break repair via nonhomologous end joining; ectopic germ cell programmed cell death; heart development; immune system process; immunoglobulin production; immunoglobulin V(D)J recombination; innate immune response; intrinsic apoptotic signaling pathway in response to DNA damage; lymphocyte differentiation; negative regulation of apoptotic process; negative regulation of cellular senescence; negative regulation of immunoglobulin production; negative regulation of protein phosphorylation; negative regulation of response to gamma radiation; peptidyl-serine phosphorylation; phosphorylation; positive regulation of apoptotic process; positive regulation of developmental growth; positive regulation of double-strand break repair via nonhomologous end joining; positive regulation of fibroblast proliferation; positive regulation of immune system process; positive regulation of transcription by RNA polymerase II; pro-B cell differentiation; protein destabilization; protein phosphorylation; regulation of circadian rhythm; regulation of epithelial cell proliferation; regulation of smooth muscle cell proliferation; response to gamma radiation; response to ionizing radiation; rhythmic process; signal transduction involved in mitotic G1 DNA damage checkpoint; somitogenesis; spleen development; T cell differentiation in thymus; T cell lineage commitment; T cell receptor V(D)J recombination; telomere capping; telomere maintenance; thymus development; V(D)J recombination