Tchem PRKDC DNA-dependent protein kinase catalytic subunit

Protein Summary

Description

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. 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 mechanism. Interacts with CRY1 and CRY2; negatively regulates CRY1 phosphorylation. 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. 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]

Uniprot Accession IDs

• P78527
• P78528
• Q13327
• Q13337
• Q14175
• Q59H99
• Q7Z611
• Q96SE6
• Q9UME3
• DNA-PK catalytic subunit

Gene Name

• PRKDC

Ensembl ID

• ENST00000314191
• ENSP00000313420
• ENSG00000253729
• ENST00000338368
• ENSP00000345182

Symbol

• HYRC
• HYRC1
• HYRC
• p350
• DNAPK
• DNPK1
• HYRC1
• IMD26
• XRCC7
• DNAPKc
• DNA-PKC
• DNA-PKcs

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
interacting protein	1
protein domain	0.99
molecular function	0.98

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Dna-dependent Protein Kinase Catalytic Subunit

Protein / Transferase / Kinase / Nucleotide Kinase / Dna-dependent Protein Kinase Catalytic Subunit

Protein / Nucleic Acid Binding / Dna-dependent Protein Kinase Catalytic Subunit

DTO Classes

Protein / Kinase / Protein Kinase / Atypical Group / Pikk Family / Dnapk Subfamily / Dna-dependent Protein Kinase Catalytic Subunit

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1060.38   (req: < 5)

Gene RIFs: 326   (req: <= 3)

Antibodies: 1451   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1060.38   (req: >= 5)

Gene RIFs: 326   (req: > 3)

Antibodies: 1451   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 53

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 176

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0