PRKDC
Entrez ID: 5591
Full name: protein kinase, DNA-activated, catalytic subunit
External links: HGNC UniprotKB Ensembl RefSeq COSMIC
Family: Atypical: PIKK: DNAPK
Chromosomal location: 8q11.21
Substructure location: Gatekeeper: A-loop: G-loop: αC-helix:
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PRKDC
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 (PubMed:11955432, PubMed:12649176, PubMed:14734805). Must be bound to DNA to express its catalytic p...
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 (PubMed:11955432, PubMed:12649176, PubMed:14734805). 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) (PubMed:11955432). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). Required to protect and align broken ends of DNA (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). May also act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). 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 (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). Recognizes the substrate consensus sequence [ST]-Q (PubMed:15574326, PubMed:11955432, PubMed:12649176, PubMed:14734805). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). 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 (PubMed:2507541, PubMed:2247066, PubMed:1597196, PubMed:8407951, PubMed:8464713, PubMed:9362500, PubMed:9139719, PubMed:10026262, PubMed:10467406, PubMed:12509254, PubMed:11889123, PubMed:14612514, PubMed:14704337, PubMed:16397295, PubMed:26237645, PubMed:28712728). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). 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 (By similarity). 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 (PubMed:28712728).
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GO - Biological processes (BP):
activation of innate immune response, B cell lineage commitment, brain development, cellular protein modification process, cellular response to DNA damage stimulus, cellular response to insulin stimulus, double-strand break repair, double-strand break repair via alternative nonhomologous end joining...
activation of innate immune response, B cell lineage commitment, brain development, cellular protein modification process, cellular response to DNA damage stimulus, cellular response to insulin stimulus, double-strand break repair, double-strand break repair via alternative nonhomologous end joining, double-strand break repair via nonhomologous end joining, ectopic germ cell programmed cell death, heart development, immunoglobulin V(D)J recombination, innate immune response, intrinsic apoptotic signaling pathway in response to DNA damage, 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, 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 transcription by RNA polymerase II, positive regulation of type I interferon production, pro-B cell differentiation, protein destabilization, protein phosphorylation, protein ubiquitination, regulation of circadian rhythm, regulation of epithelial cell proliferation, regulation of smooth muscle cell proliferation, response to activity, response to gamma 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
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GO - Molecular function (MF):
ATP binding, DNA-dependent protein kinase activity, double-stranded DNA binding, enzyme binding, protein domain specific binding, protein kinase activity, protein serine/threonine kinase activity, RNA binding, transcription factor binding...
ATP binding, DNA-dependent protein kinase activity, double-stranded DNA binding, enzyme binding, protein domain specific binding, protein kinase activity, protein serine/threonine kinase activity, RNA binding, transcription factor binding
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GO - Cellular component (CC):
cytosol, DNA-dependent protein kinase-DNA ligase 4 complex, nuclear chromosome, telomeric region, nucleolus, nucleoplasm, nucleus, membrane, nonhomologous end joining complex, protein-containing complex, protein-DNA complex, transcription factor complex...
cytosol, DNA-dependent protein kinase-DNA ligase 4 complex, nuclear chromosome, telomeric region, nucleolus, nucleoplasm, nucleus, membrane, nonhomologous end joining complex, protein-containing complex, protein-DNA complex, transcription factor complex
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protein kinase, DNA-activated, catalytic subunit
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Kaplan plot for PRKDC in
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*NOTE: the Kaplan plots were collected from OncoLnc