DNA-PKCS (phospho Thr2638) Rabbit Polyclonal Antibody

This gene encodes the catalytic subunit of the DNA-dependent protein kinase (DNA-PK) . It functions with the Ku70/Ku80 heterodimer protein in DNA double strand break repair and recombination. The protein encoded is a member of the PI3/PI4-kinase family.[provided by RefSeq, Jul 2010], catalytic activity:ATP + a protein = ADP + a phosphoprotein., enzyme regulation:Inhibited by wortmannin. Activity of the enzyme seems to be attenuated by autophosphorylation., function:Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA nonhomologous 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, c-myc/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 TP53/p53 in the presence of supercoiled DNA is dependent on C1D., PTM:Phosphorylated upon DNA damage, probably by ATM or ATR. Autophosphorylated on Thr-2609, Thr-2638 and Thr-2647. Thr-2609 is a DNA damage-inducible phosphorylation site (inducible with ionizing radiation, IR) . Autophosphorylation induces a conformational change that leads to remodeling of the DNA-PK complex, requisite for efficient end processing and DNA repair., similarity:Belongs to the PI3/PI4-kinase family., similarity:Contains 1 FAT domain., similarity:Contains 1 FATC domain., similarity:Contains 1 PI3K/PI4K domain., similarity:Contains 2 HEAT repeats., similarity:Contains 3 TPR repeats., subunit:DNA-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.