PRKDC - DNA-dependent protein kinase catalytic subunit - human protein (Function)
 
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PRKDC »  DNA-dependent protein kinase catalytic subunit   [ EC 2.7.11.1 ]  (DNA-PKcs)
 
Protein also known as:  DNPK1.
Gene name:  PRKDC
Family name: PI3/PI4-kinase
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 243 2
GENE REF ISO

Function

 show evidences
Overview 
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, 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.  
4
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
DNA bindingdefinition[GO:0003677]  
  • IEAUniProtKB KW
DNA-dependent protein kinase activitydefinition[GO:0004677]  
1
  • IDAMGI
Enzyme bindingdefinition[GO:0019899] silver  
  • IEAOrtholog Compara
Poly(A) RNA bindingdefinition[GO:0044822]  
2
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
9
  • IPIIntAct
  • IPIUniProtKB
Protein kinase activitydefinition[GO:0004672]  
1
  • TASPINC
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • IDABHF-UCL
Transcription factor bindingdefinition[GO:0008134]  
1
  • IPIBHF-UCL
GO biological process 
B cell lineage commitmentdefinition[GO:0002326] silver  
  • IEAOrtholog Compara
Brain developmentdefinition[GO:0007420] silver  
  • IEAOrtholog Compara
Cellular protein modification processdefinition[GO:0006464]  
1
  • TASPINC
Cellular response to insulin stimulusdefinition[GO:0032869]  
1
  • IMPBHF-UCL
Ectopic germ cell programmed cell deathdefinition[GO:0035234] silver  
  • IEAOrtholog Compara
Heart developmentdefinition[GO:0007507] silver  
  • IEAOrtholog Compara
Immunoglobulin V(D)J recombinationdefinition[GO:0033152] silver  
  • IEAOrtholog Compara
Intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:0008630] silver  
  • IEAOrtholog Compara
Negative regulation of protein phosphorylationdefinition[GO:0001933]  
  • ISSOrtholog Curator
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
2
  • IDABHF-UCL
  • IDAMGI
Positive regulation of apoptotic processdefinition[GO:0043065] silver  
  • IEAOrtholog Compara
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
1
  • IMPBHF-UCL
Pro-B cell differentiationdefinition[GO:0002328] silver  
  • IEAOrtholog Compara
Protein destabilizationdefinition[GO:0031648] silver  
  • IEAOrtholog Compara
Regulation of circadian rhythmdefinition[GO:0042752]  
  • ISSOrtholog Curator
Response to gamma radiationdefinition[GO:0010332] silver  
  • IEAOrtholog Compara
Somitogenesisdefinition[GO:0001756] silver  
  • IEAOrtholog Compara
T cell differentiation in thymusdefinition[GO:0033077] silver  
  • IEAOrtholog Compara
T cell lineage commitmentdefinition[GO:0002360] silver  
  • IEAOrtholog Compara
T cell receptor V(D)J recombinationdefinition[GO:0033153] silver  
  • IEAOrtholog Compara
Telomere maintenancedefinition[GO:0000723] silver  
  • IEAOrtholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It is regulated in the following manner
Inhibited by wortmannin. Activity of the enzyme seems to be attenuated by autophosphorylation.  
1
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Cell cycle  hsa04110+5591  
Non-homologous end-joining  hsa03450+5591  
According to Reactome, this protein belongs to the following pathways:
DNA Repair  REACT_216  
Immune System  REACT_6900  
 

Keywords

Biological process 
DNA damage  definition   [KW-0227]
DNA recombination  definition   [KW-0233]
DNA repair  definition   [KW-0234]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: DNA-PKcs
GenomeRNAi: 5591
PRO: PR:P78527