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MGP002432

UniProt Annotations

Entry Information
Gene Nameprotein kinase, DNA-activated, catalytic polypeptide
Protein EntryPRKDC_HUMAN
UniProt IDP78527
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=P78527-1; Sequence=Displayed; Name=2; IsoId=P78527-2; Sequence=VSP_004708;
Catalytic ActivityATP + a protein = ADP + a phosphoprotein.
Enzyme RegulationInhibited by wortmannin. Activity of the enzyme seems to be attenuated by autophosphorylation. {ECO:0000269|PubMed:9766667}.
FunctionSerine/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, 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 machanism. Interacts with CRY1 and CRY2; negatively regulates CRY1 phosphorylation. {ECO:0000269|PubMed:12649176, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:9679063}.
InteractionO43918:AIRE; NbExp=2; IntAct=EBI-352053, EBI-1753081; P42575:CASP2; NbExp=4; IntAct=EBI-352053, EBI-520342; P14921:ETS1; NbExp=2; IntAct=EBI-352053, EBI-913209; P50549:ETV1; NbExp=2; IntAct=EBI-352053, EBI-3905068; P09629:HOXB7; NbExp=2; IntAct=EBI-352053, EBI-1248457; P17936:IGFBP3; NbExp=2; IntAct=EBI-352053, EBI-715709; Q9BPZ7:MAPKAP1; NbExp=2; IntAct=EBI-352053, EBI-749938; Q9HB75:PIDD1; NbExp=6; IntAct=EBI-352053, EBI-520427; P17947:SPI1; NbExp=2; IntAct=EBI-352053, EBI-2293548; P13010:XRCC5; NbExp=6; IntAct=EBI-352053, EBI-357997; P12956:XRCC6; NbExp=5; IntAct=EBI-352053, EBI-353208; P25490:YY1; NbExp=2; IntAct=EBI-352053, EBI-765538;
PtmAutophosphorylated on Ser-2056, Thr-2609, Thr-2638 and Thr- 2647. Ser-2056 and Thr-2609 are DNA damage-inducible phosphorylation sites (inducible with ionizing radiation, IR) dephosphorylated by PPP5C. Autophosphorylation induces a conformational change that leads to remodeling of the DNA-PK complex, requisite for efficient end processing and DNA repair. {ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:11889123, ECO:0000269|PubMed:12186630, ECO:0000269|PubMed:12231622, ECO:0000269|PubMed:12509254, ECO:0000269|PubMed:14612514, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:14704337, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:1597196, ECO:0000269|PubMed:16046194, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:17081983, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:18691976, ECO:0000269|PubMed:19369195, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692, ECO:0000269|PubMed:2247066, ECO:0000269|PubMed:2507541, ECO:0000269|PubMed:8407951, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:8804412, ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9362500, ECO:0000269|PubMed:9363941}.
PtmPolyubiquitinated by RNF144A, leading to proteasomal degradation. {ECO:0000269|PubMed:24979766}.
PtmS-nitrosylated by GAPDH. {ECO:0000250}.
SimilarityBelongs to the PI3/PI4-kinase family. {ECO:0000305}.
SimilarityContains 1 FATC domain. {ECO:0000255|PROSITE- ProRule:PRU00535}.
SimilarityContains 1 FAT domain. {ECO:0000255|PROSITE- ProRule:PRU00534}.
SimilarityContains 1 PI3K/PI4K domain. {ECO:0000255|PROSITE- ProRule:PRU00269}.
SimilarityContains 2 HEAT repeats. {ECO:0000305}.
SimilarityContains 3 TPR repeats. {ECO:0000305}.
Subcellular LocationNucleus. Nucleus, nucleolus.
SubunitDNA-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. Interacts with TTI1 and TELO2. Interacts with CIB1. {ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:14744996, ECO:0000269|PubMed:15071507, ECO:0000269|PubMed:15456891, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:15758953, ECO:0000269|PubMed:15811628, ECO:0000269|PubMed:15936993, ECO:0000269|PubMed:20427287, ECO:0000269|PubMed:20801936, ECO:0000269|PubMed:20810650, ECO:0000269|PubMed:9372844, ECO:0000269|PubMed:9442054, ECO:0000269|PubMed:9679063}.
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/prkdc/";
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