Summary

Name PRKDC
Full Name DNA-dependent protein kinase catalytic subunit
Synonyms DNA-PK catalytic subunit, DNA-PKcs, DNPK1, p460 | HYRC, HYRC1
Primary ID P78527
Links - -
Type protein
Relations 67
Pathways Cell cycle: G2/M phase transition
Inhibitors PP121; 8-(4-dibenzothiophenyl)-2-(4-morpholinyl)-1-benzopyran-4-one; PIK-75 Hydrochloride; PI-103
Function 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). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). 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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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates activity img/direct_inhibition.png phosphorylation RPA2 0.604
Publications: 3 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation PNKP 0.634
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MCC 0.2
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CASP2 0.304
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TP53 0.785
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ up-regulates img/direct-activation.png phosphorylation PRKDC 0.2
Publications: 2 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ down-regulates img/direct_inhibition.png phosphorylation POU2F1 0.335
Publications: 2 Organism: Homo Sapiens
+ img/unknown.png phosphorylation NHEJ1 0.656
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png phosphorylation JUN 0.416
Publications: 1 Organism: In Vitro
+ up-regulates activity img/direct-activation.png phosphorylation PRKDC 0.2
Publications: 7 Organism: Homo Sapiens, In Vitro
Pathways:Cell cycle: G2/M phase transition
+ up-regulates activity img/direct-activation.png phosphorylation XRCC6 0.939
Publications: 2 Organism: Homo Sapiens
+ img/unknown.png phosphorylation RPA2 0.604
Publications: 3 Organism: In Vitro, Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation SRF 0.417
Publications: 2 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation WRN 0.668
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation AKT1 0.744
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation AKT 0.744
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ up-regulates img/direct-activation.png phosphorylation DCLRE1C 0.686
Publications: 3 Organism: Homo Sapiens
+ img/unknown.png phosphorylation NR3C1 0.356
Publications: 1 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation HNRNPU 0.389
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation LIG4 0.8
Publications: 3 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation PNPT1 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation TDP1 0.516
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation PDX1 0.31
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png phosphorylation IRF3 0.401
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation GOLPH3 0.323
Publications: 2 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation H1-2 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation POLL 0.44
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation RPA2 0.604
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation FH 0.2
Publications: 1 Organism: In Vitro
+ up-regulates img/direct-activation.png phosphorylation PRKDC 0.319
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ up-regulates img/direct-activation.png phosphorylation PRKDC 0.686
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ down-regulates img/direct_inhibition.png phosphorylation PRKDC 0.2
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ img/unknown.png phosphorylation HSP90AA1 0.44
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CHEK2 0.615
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ up-regulates activity img/direct-activation.png binding PRKDC 0.339
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png relocalization PRKDC 0.939
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition PRKDC 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition PRKDC 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition PRKDC 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination PRKDC 0.544
Publications: 1 Organism: Homo Sapiens
+ form complex img/form-complex.png binding DNA-PK 0.933
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation H2AX 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation USF1 0.297
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition PRKDC 0.8
Publications: 1 Organism: Homo Sapiens