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  3. PRKDC

PRKDC (Protein kinase, DNA-activated, catalytic polypeptide)

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The Function of PRKDC

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 machanism. Interacts with CRY1 and CRY2; negatively regulates CRY1 phosphorylation.

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Protein names

Recommended name:

DNA-dependent protein kinase catalytic subunit

Alternative name(s):

DNA-PK catalytic subunit
DNA-PKcs
DNPK1
p460

PRKDC SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS7003908 (PRKDC) ??
  2. RS8178085 (PRKDC) ??

Top Gene-Substance Interactions

PRKDC Interacts with These Diseases

Disease Score

Substances That Increase PRKDC

Substances Interaction Organism Category

Substances That Decrease PRKDC

Substances Interaction Organism Category

Advanced Summary

     From NCBI Gene: Immunodeficiency 26 with or without neurologic abnormalitiesFrom UniProt: Immunodeficiency 26 with or without neurologic abnormalities (IMD26): A form of severe combined immunodeficiency characterized by reduced or absent T and B cells, recurrent candidiasis, and lower respiratory tract infections. Some patients show dysmorphic features, severe growth failure, microcephaly, seizures, and impaired neurological functions. [MIM:615966]

     From NCBI Gene: 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] From UniProt: 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 machanism. Interacts with CRY1 and CRY2; negatively regulates CRY1 phosphorylation.

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • p53

Gene Pathways:

  • Immune System
  • DNA Repair
  • DNA replication and repair
  • Non-homologous end-joining

Enzyme Regulation:

Inhibited by wortmannin. Activity of the enzyme seems to be attenuated by autophosphorylation.

Molecular Function:

  • Atp Binding
  • Dna-Dependent Protein Kinase Activity
  • Double-Stranded Dna Binding
  • Poly(A) Rna Binding
  • Protein Serine/Threonine Kinase Activity
  • Transcription Factor Binding

Biological Processes:

  • B Cell Lineage Commitment
  • Brain Development
  • Cell Proliferation
  • Cellular Protein Modification Process
  • Cellular Response To Insulin Stimulus
  • Double-Strand Break Repair
  • Double-Strand Break Repair Via Alternative Nonhomologous End Joining
  • Double-Strand Break Repair Via Nonhomologous End Joining
  • Ectopic Germ Cell Programmed Cell Death
  • Heart Development
  • Immunoglobulin V(D)J Recombination
  • Intrinsic Apoptotic Signaling Pathway In Response To Dna Damage
  • Negative Regulation Of Apoptotic Process
  • Negative Regulation Of Cellular Senescence
  • Negative Regulation Of Immunoglobulin Production
  • Negative Regulation Of Protein Phosphorylation
  • Negative Regulation Of Response To Gamma Radiation
  • Peptidyl-Serine Phosphorylation
  • Positive Regulation Of Apoptotic Process
  • Positive Regulation Of Developmental Growth
  • Positive Regulation Of Fibroblast Proliferation
  • Positive Regulation Of Immune System Process
  • Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
  • Positive Regulation Of Type I Interferon Production
  • Pro-B Cell Differentiation
  • Protein Destabilization
  • Regulation Of Circadian Rhythm
  • Regulation Of Smooth Muscle Cell Proliferation
  • Response To Gamma Radiation
  • Rhythmic Process
  • Signal Transduction Involved In Mitotic G1 Dna Damage Checkpoint
  • Somitogenesis
  • Spleen Development
  • T Cell Differentiation In Thymus
  • T Cell Lineage Commitment
  • T Cell Receptor V(D)J Recombination
  • Telomere Capping
  • Thymus Development

Drug Bank:

  • Caffeine
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| AS27_05838| AS28_00713| CB1_000270019| DNA-activated protein kinase catalytic polypeptide| DNA-dependent protein kinase catalytic subunit| DNAPDcs| DNAPK| DNA-PK| DNA-PK catalytic subunit| dnapkcs| dna-pkcs| DNA protein kinase catalytic subunit| DNPK1| DOXNPH| doxorubicin nephropathy| dxnph| fa96e12| H920_07947| hyper-radiosensitivity of murine scid mutation, complementing 1| HYRC| hyrc1| I79_017613| IMD26| M959_00903| N300_12888| N301_05513| N302_13343| N303_02954| N305_14429| N306_00841| N307_02295| N308_10193| N310_03635| N311_06756| N312_12470| N320_01628| N321_06511| N322_11856| N324_04852| N326_12930| N328_04300| N329_01932| N330_06311| N331_02484| N332_00797| N334_13586| N335_03000| N336_03375| N339_04127| N340_02202| N341_02229| p350| p460| PAL_GLEAN10001311| PANDA_016578| protein kinase catalytic subunit (DNA-dependent protein kinase)| protein kinase, DNA activated, catalytic polypeptide| scid| severe combined immunodeficiency| slip| UY3_06094| xrcc7| Y1Q_017240| Z169_08722| prkdc

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