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DNAPK an atypical protein kinase of the PIKK family. Involved in DNA nonhomologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. and modulation of transcription. 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. Defects cause severe combined immune deficiency (SCID) which is characterized by a lack of mature functional lymphocytes and a high susceptibility to lethal opportunistic infections. Required for repair of radiation-induced dsDNA breaks. Loss of function in mice or horses leads to the SCID (severe combined immune deficiency) phenotype due to failure of immunoglobulin rearrangement. Target of mutation in mismatch repair-deficient colorectal cancer. Inhibitor: KU-7059. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: ATYPICAL group; DNA repair, damage; DNAPK subfamily; EC; Kinase, protein; Nucleolus; PIKK family; Protein kinase, Ser/Thr (non-receptor); Protein kinase, atypical
Chromosomal Location of Human Ortholog: 8q11.21
Cellular Component: cytosol; DNA-dependent protein kinase complex; extracellular matrix; membrane; nuclear chromosome, telomeric region; nucleolus; nucleoplasm; nucleus; protein complex; transcription factor complex
Molecular Function: DNA-dependent protein kinase activity; double-stranded DNA binding; protein binding; protein domain specific binding; protein kinase activity; protein serine/threonine kinase activity; RNA binding; transcription factor binding
Biological Process: cell proliferation; cellular response to insulin stimulus; double-strand break repair; double-strand break repair via nonhomologous end joining; negative regulation of apoptosis; negative regulation of protein amino acid phosphorylation; peptidyl-serine phosphorylation; positive regulation of interferon type I production; positive regulation of transcription from RNA polymerase II promoter; protein amino acid phosphorylation; protein modification process; protein ubiquitination; regulation of circadian rhythm; regulation of smooth muscle cell proliferation; telomere capping
Disease: Immunodeficiency 26 With Or Without Neurologic Abnormalities
Reference #:  P78527 (UniProtKB)
Alt. Names/Synonyms: DNA-dependent protein kinase catalytic subunit; DNA-PK catalytic subunit; DNA-PKcs; DNAPK; DNPK1; hyper-radiosensitivity of murine scid mutation, complementing 1; HYRC; HYRC1; p350; p460; PRKDC; protein kinase, DNA-activated, catalytic polypeptide; XRCC7
Gene Symbols: PRKDC
Molecular weight: 469,089 Da
Basal Isoelectric point: 6.75  Predict pI for various phosphorylation states
CST Pathways:  ErbB/HER Signaling  |  G2/M DNA Damage Checkpoint
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