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PRKDC - protein kinase, DNA-activated, catalytic subunit (human)

Gene
Symbol
Dates
  • Create:
    2016-09-14
  • Modify:
    2025-01-29
Description
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]
Enables several functions, including RNA polymerase II-specific DNA-binding transcription factor binding activity; nucleic acid binding activity; and protein serine/threonine kinase activity. Involved in several processes, including positive regulation of nucleobase-containing compound metabolic process; regulation of innate immune response; and ribosome biogenesis. Acts upstream of or within peptidyl-serine phosphorylation. Located in nucleolus and nucleoplasm. Part of several cellular components, including nucleus; protein-DNA complex; and small-subunit processome. Is active in chromatin. Implicated in immunodeficiency 26.

1 Names and Identifiers

1.1 Synonyms

  • DNA-PKC
  • DNA-PKcs
  • DNAPK
  • DNAPKc
  • DNPK1
  • HYRC
  • HYRC1
  • IMD26
  • XRCC7
  • p350
  • DNA-dependent protein kinase catalytic subunit
  • DNA-PK catalytic subunit
  • hyper-radiosensitivity of murine scid mutation, complementing 1
  • p460
  • protein kinase, DNA-activated, catalytic polypeptide

1.2 Other Identifiers

1.2.1 HGNC ID

1.2.2 Ensembl ID

1.2.3 Alliance Gene ID

1.2.4 Bgee Gene ID

1.2.5 Enzyme Commission (EC) Number

1.2.6 GenCC ID

1.2.7 KEGG Gene

1.2.8 MIM Number

1.2.9 NCI Thesaurus Code

1.2.10 Open Targets ID

1.2.11 PharmGKB ID

1.2.12 Pharos Target

1.2.13 VEuPathDB ID

1.2.14 Wikidata

3 Proteins

3.1 Protein Function

Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PMID: 11955432, PMID: 12649176, PMID: 14734805, PMID: 33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PMID: 11955432, PMID: 12649176, PMID: 14734805, PMID: 33854234, PMID: 34352203). Must be bound to DNA to express its catalytic properties (PMID: 11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PMID: 11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PMID: 11955432, PMID: 12649176, PMID: 14734805, PMID: 15574326, PMID: 33854234). Act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PMID: 11955432, PMID: 12649176, PMID: 14734805, PMID: 15574326). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PMID: 11955432, PMID: 12649176, PMID: 14734805, PMID: 15574326). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PMID: 11955432, PMID: 12649176, PMID: 14734805, PMID: 15574326). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PMID: 32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PMID: 32103174). Recognizes the substrate consensus sequence [ST]-Q (PMID: 11955432, PMID: 12649176, PMID: 14734805, PMID: 15574326). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PMID: 14627815, PMID: 16046194). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PMID: 10026262, PMID: 10467406, PMID: 11889123, PMID: 12509254, PMID: 14599745, PMID: 14612514, PMID: 14704337, PMID: 15177042, PMID: 1597196, PMID: 16397295, PMID: 18644470, PMID: 2247066, PMID: 2507541, PMID: 26237645, PMID: 26666690, PMID: 28712728, PMID: 29478807, PMID: 30247612, PMID: 8407951, PMID: 8464713, PMID: 9139719, PMID: 9362500). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PMID: 9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PMID: 9363941). 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 (By similarity). 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 (PMID: 28712728). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PMID: 33273464). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (PMID: 35460603).

3.2 Protein Isoforms

Isoform
Isoform 1
UniProt ID
RefSeq Accession
Isoform
Isoform 2
UniProt ID
RefSeq Accession

3.3 Protein 3D Structures

3.3.1 PDB Structures

3.3.2 NCBI Protein Structures

3.3.3 AlphaFold Structures

Highly accurate protein structure prediction with AlphaFold. Nature. 2021 Aug;596(7873):583-589. DOI:10.1038/s41586-021-03819-2. PMID:34265844; PMCID:PMC8371605

3.4 Protein Targets

4 Chemicals and Bioactivities

4.1 Tested Compounds

5 BioAssays

5.1 Small-Molecule BioAssays

5.2 RNAi BioAssays

6 Diseases and Phenotypes

6.1 KEGG Diseases

6.2 OMIM Phenotypes

6.3 MedGen Diseases

6.4 Gene-Disease Associations

7 Interactions and Pathways

7.1 Chemical-Gene Interactions

7.2 Interactions

7.3 Pathways

8 Biochemical Reactions

9 Expression

10 Target Development Level

11 Literature

11.1 Consolidated References

11.2 Gene-Chemical Co-Occurrences in Literature

11.3 Gene-Gene Co-Occurrences in Literature

11.4 Gene-Disease Co-Occurrences in Literature

12 Patents

12.1 Gene-Chemical Co-Occurrences in Patents

12.2 Gene-Gene Co-Occurrences in Patents

12.3 Gene-Disease Co-Occurrences in Patents

13 Classification

13.1 Gene Family

13.2 NCI Thesaurus Tree

13.3 Gene Ontology: Biological Process

13.4 Gene Ontology: Cellular Component

13.5 Gene Ontology: Molecular Function

13.6 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

13.7 ChEMBL Target Tree

13.8 Enzyme Classification

14 Information Sources

  1. NCBI Gene
    LICENSE
    NCBI Website and Data Usage Policies and Disclaimers
    https://www.ncbi.nlm.nih.gov/home/about/policies/
  2. PubChem
  3. Alliance of Genome Resources
    LICENSE
    All annotations and data produced by Alliance members that are accessible from alliancegenome.org are distributed under a CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
    https://www.alliancegenome.org/privacy-warranty-licensing
  4. BindingDB
    LICENSE
    All data curated by BindingDB staff are provided under the Creative Commons Attribution 3.0 License (https://creativecommons.org/licenses/by/3.0/us/).
    https://www.bindingdb.org/rwd/bind/info.jsp
  5. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  6. Chemical Probes Portal
  7. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  8. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  9. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  10. IUPHAR/BPS Guide to PHARMACOLOGY
    LICENSE
    The Guide to PHARMACOLOGY database is licensed under the Open Data Commons Open Database License (ODbL) https://opendatacommons.org/licenses/odbl/. Its contents are licensed under a Creative Commons Attribution-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-sa/4.0/)
    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  11. Therapeutic Target Database (TTD)
  12. Toxin and Toxin Target Database (T3DB)
    LICENSE
    T3DB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (T3DB) and the original publication.
    http://www.t3db.ca/downloads
  13. BioGRID
    LICENSE
    The MIT License (MIT); Copyright Mike Tyers Lab
    https://wiki.thebiogrid.org/doku.php/terms_and_conditions
  14. Database of Interacting Proteins (DIP)
    LICENSE
    All DIP database records available under the terms set by the Creative Commons Attribution-NoDerivs License.
    https://dip.doe-mbi.ucla.edu/dip/termsofuse.html
  15. STRING: functional protein association networks
  16. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  17. Gene Curation Coalition (GenCC)
    LICENSE
    The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication.
    https://thegencc.org/terms.html
    PRKDC
  18. HUGO Gene Nomenclature Committee (HGNC)
    LICENSE
    No restrictions are imposed on access to, or use of, the data provided by the HGNC, which are provided to enhance knowledge and encourage progress in the scientific community.
    https://www.genenames.org/about/
  19. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
  20. NCBI Gene Expression Omnibus (GEO)
  21. NCBI MedGen
    LICENSE
    NCBI Website and Data Usage Policies and Disclaimers
    https://www.ncbi.nlm.nih.gov/home/about/policies/
  22. NCBI Structure
    LICENSE
    NCBI Website and Data Usage Policies and Disclaimers
    https://www.ncbi.nlm.nih.gov/home/about/policies/
  23. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  24. Online Mendelian Inheritance in Man (OMIM)
    LICENSE
    The OMIM database is made available to the general public subject to certain restrictions.
    https://omim.org/help/copyright
  25. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  26. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  27. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
    Data files contained in the PDB archive (ftp://ftp.wwpdb.org) are free of all copyright restrictions and made fully and freely available for both non-commercial and commercial use. Users of the data should attribute the original authors of that structural data.
    https://www.rcsb.org/pages/policies
  28. Swiss Institute of Bioinformatics Bgee
    LICENSE
    Creative Commons Zero license (CC0)
    https://www.bgee.org/about/
  29. UniProt
    LICENSE
    We have chosen to apply the Creative Commons Attribution (CC BY 4.0, http://creativecommons.org/licenses/by/4.0/) License to all copyrightable parts of our databases.
    https://www.uniprot.org/help/license
  30. VEuPathDB: The Eukaryotic Pathogen, Vector and Host Informatics Resource
    LICENSE
    All data on VEuPathDB websites are provided freely for public use.
    https://veupathdb.org/veupathdb/app/static-content/about.html
  31. Wikidata
  32. Swiss Institute of Bioinformatics ENZYME
    LICENSE
    Copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution (CC BY 4.0) License (https://creativecommons.org/licenses/by/4.0/).
    https://enzyme.expasy.org/enzyme.get
    Enzyme Classification
    https://enzyme.expasy.org/
  33. Gene Ontology (GO)
    LICENSE
    Gene Ontology Consortium data and data products are licensed under the Creative Commons Attribution 4.0 Unported License (https://creativecommons.org/licenses/by/4.0/legalcode)
    http://geneontology.org/docs/go-citation-policy/
  34. AlphaFold DB
    LICENSE
    All of the data provided is freely available for both academic and commercial use under Creative Commons Attribution 4.0 (CC-BY 4.0) licence terms.
    https://alphafold.ebi.ac.uk/faq
  35. Rhea - annotated reactions database
    LICENSE
    Rhea has chosen to apply the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). This means that you are free to copy, distribute, display and make commercial use of the database in all legislations, provided you credit (cite) Rhea.
    https://www.rhea-db.org/help/license-disclaimer
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