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Aliases for PRKDC Gene

Aliases for PRKDC Gene

  • Protein Kinase, DNA-Activated, Catalytic Polypeptide 2 3
  • HYRC1 3 4 6
  • DNPK1 3 4 6
  • DNA-PK Catalytic Subunit 3 4
  • EC 2.7.11.1 4 64
  • DNA-PKcs 3 4
  • HYRC 3 4
  • P460 3 4
  • Hyper-Radiosensitivity Of Murine Scid Mutation, Complementing 1 3
  • DNA-Dependent Protein Kinase Catalytic Subunit 3
  • DNAPK 3
  • IMD26 3
  • XRCC7 3
  • P350 3

External Ids for PRKDC Gene

Previous Symbols for PRKDC Gene

  • HYRC
  • HYRC1

Summaries for PRKDC Gene

Entrez Gene Summary for PRKDC 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]

GeneCards Summary for PRKDC Gene

PRKDC (Protein Kinase, DNA-Activated, Catalytic Polypeptide) is a Protein Coding gene. Diseases associated with PRKDC include severe combined immunodeficiency due to dna-pkcs deficiency and immunodeficiency 16, with or without neurologic abnormalities. Among its related pathways are Akt Signaling and ERK Signaling. GO annotations related to this gene include protein serine/threonine kinase activity and enzyme binding. An important paralog of this gene is ATR.

UniProtKB/Swiss-Prot for PRKDC Gene

  • 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.

Tocris Summary for PRKDC Gene

  • DNA-dependent protein kinase (DNA-PK) is a nuclear protein serine/threonine kinase that is a molecular sensor of DNA damage. DNA-PK is involved in the ligation step of the non-homologous end joining (NHEJ) pathway of DNA double strand break (DSB) repair, V(D)J recombination and telomere stabilization. DNA-PK is activated by phosphorylation by ATM/ATR following DNA damage and is inhibited by wortmannin. DNA-PK must be bound to DNA in order to exhibit its catalytic properties and has multiple targets including c-Abl, histone H1, c-jun, p53, c-MYC and more.

Gene Wiki entry for PRKDC Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PRKDC Gene

Genomics for PRKDC Gene

Genomic Location for PRKDC Gene

Start:
47,773,108 bp from pter
End:
47,960,183 bp from pter
Size:
187,076 bases
Orientation:
Minus strand

Genomic View for PRKDC Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for PRKDC Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PRKDC Gene

Regulatory Elements for PRKDC Gene

Proteins for PRKDC Gene

  • Protein details for PRKDC Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P78527-PRKDC_HUMAN
    Recommended name:
    DNA-dependent protein kinase catalytic subunit
    Protein Accession:
    P78527
    Secondary Accessions:
    • P78528
    • Q13327
    • Q13337
    • Q14175
    • Q59H99
    • Q7Z611
    • Q96SE6
    • Q9UME3

    Protein attributes for PRKDC Gene

    Size:
    4128 amino acids
    Molecular mass:
    469089 Da
    Quaternary structure:
    • Interacts with SETX (PubMed:23149945). 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. Interacts with TTI1 and TELO2. Interacts with CIB1.

    Alternative splice isoforms for PRKDC Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PRKDC Gene

Proteomics data for PRKDC Gene at MOPED

Post-translational modifications for PRKDC Gene

  • Autophosphorylated on Ser-2056, Thr-2609, Thr-2638 and Thr-2647. Ser-2056 and Thr-2609 are DNA damage-inducible phosphorylation sites (inducible with ionizing radiation, IR) dephosphorylated by PPP5C. Autophosphorylation induces a conformational change that leads to remodeling of the DNA-PK complex, requisite for efficient end processing and DNA repair.
  • Polyubiquitinated by RNF144A, leading to proteasomal degradation.
  • S-nitrosylated by GAPDH.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys108, Lys117, Lys148, Lys205, Lys225, Lys236, Lys254, Lys263, Lys310, Lys337, Lys357, Lys374, Lys471, Lys493, Lys520, Lys525, Lys681, Lys689, Lys692, Lys700, Lys801, Lys810, Lys824, Lys828, Lys838, Lys868, Lys881, Lys963, Lys1042, Lys1051, Lys1057, Lys1074, Lys1193, Lys1209, Lys1334, Lys1361, Lys1407, Lys1412, Lys1422, Lys1456, Lys1489, Lys1617, Lys1627, Lys1642, Lys1744, Lys1807, Lys1857, Lys1869, Lys1875, Lys1895, Lys1913, Lys1917, Lys1970, Lys1973, Lys1985, Lys2102, Lys2127, Lys2132, Lys2259, Lys2313, Lys2334, Lys2359, Lys2369, Lys2418, Lys2433, Lys2441, Lys2447, Lys2683, Lys2694, Lys2715, Lys2717, Lys2738, Lys2764, Lys2786, Lys2806, Lys2835, Lys2908, Lys2928, Lys2950, Lys3067, Lys3128, Lys3147, Lys3158, Lys3172, Lys3192, Lys3196, Lys3248, Lys3257, Lys3260, Lys3302, Lys3318, Lys3355, Lys3372, Lys3426, Lys3455, Lys3621, Lys3631, Lys3638, Lys3655, Lys3669, Lys3691, Lys3710, Lys3753, Lys3825, Lys3840, Lys3845, Lys3849, Lys3860, Lys3884, Lys4007, Lys4014, Lys4023, Lys4036, Lys4050, Lys4070, and Lys4105

Other Protein References for PRKDC Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for PRKDC Gene

UniProtKB/Swiss-Prot:

PRKDC_HUMAN
Domain:
  • Contains 1 FAT domain.:
    • P78527
  • Contains 1 FATC domain.:
    • P78527
  • Contains 1 PI3K/PI4K domain.:
    • P78527
Family:
  • Belongs to the PI3/PI4-kinase family.:
    • P78527
Similarity:
  • Contains 2 HEAT repeats.:
    • P78527
  • Contains 3 TPR repeats.:
    • P78527
genes like me logo Genes that share domains with PRKDC: view

No data available for Gene Families for PRKDC Gene

Function for PRKDC Gene

Molecular function for PRKDC Gene

GENATLAS Biochemistry: DNA dependent serine/threonine protein kinase catalytic subunit,dimerizing with Ku antigen (see KUP70 (CLU),KUP80),involved in DNA double-strand break repair by end joining (non homologous recombination) and V(D)J recombination,same as HYRC1
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot EnzymeRegulation: Inhibited by wortmannin. Activity of the enzyme seems to be attenuated by autophosphorylation.
UniProtKB/Swiss-Prot Function: 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.

Enzyme Numbers (IUBMB) for PRKDC Gene

Gene Ontology (GO) - Molecular Function for PRKDC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003677 DNA binding IEA --
GO:0004672 protein kinase activity IDA 7671312
GO:0004674 protein serine/threonine kinase activity IDA 19303849
GO:0004677 DNA-dependent protein kinase activity IDA 15194694
GO:0005488 binding --
genes like me logo Genes that share ontologies with PRKDC: view
genes like me logo Genes that share phenotypes with PRKDC: view

Animal Models for PRKDC Gene

MGI Knock Outs for PRKDC:

miRNA for PRKDC Gene

miRTarBase miRNAs that target PRKDC

No data available for Transcription Factor Targeting and HOMER Transcription for PRKDC Gene

Localization for PRKDC Gene

Subcellular locations from UniProtKB/Swiss-Prot for PRKDC Gene

Nucleus. Nucleus, nucleolus.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for PRKDC Gene COMPARTMENTS Subcellular localization image for PRKDC gene
Compartment Confidence
nucleus 5
cytosol 2
mitochondrion 1
plasma membrane 1

Gene Ontology (GO) - Cellular Components for PRKDC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus --
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IDA 19303849
GO:0005730 nucleolus IEA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with PRKDC: view

Pathways for PRKDC Gene

genes like me logo Genes that share pathways with PRKDC: view

Gene Ontology (GO) - Biological Process for PRKDC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000723 telomere maintenance IEA --
GO:0000724 double-strand break repair via homologous recombination IBA --
GO:0001756 somitogenesis IEA --
GO:0001933 negative regulation of protein phosphorylation ISS --
GO:0002326 B cell lineage commitment IEA --
genes like me logo Genes that share ontologies with PRKDC: view

Compounds for PRKDC Gene

(3) Tocris Compounds for PRKDC Gene

Compound Action Cas Number
DMNB DNA-PK inhibitor [20357-25-9]
NU 7026 Selective DNA-PK inhibitor [154447-35-5]
NU 7441 Potent and selective DNA-PK inhibitor [503468-95-9]

(2) HMDB Compounds for PRKDC Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0

(8) Novoseek inferred chemical compound relationships for PRKDC Gene

Compound -log(P) Hits PubMed IDs
p-350 85 10
phosphatidylinositol 56.6 5
threonine 53.1 3
pkcs 49.6 3
serine 38.1 3
genes like me logo Genes that share compounds with PRKDC: view

Transcripts for PRKDC Gene

Unigene Clusters for PRKDC Gene

Protein kinase, DNA-activated, catalytic polypeptide:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for PRKDC Gene

No ASD Table

Relevant External Links for PRKDC Gene

GeneLoc Exon Structure for
PRKDC
ECgene alternative splicing isoforms for
PRKDC

Expression for PRKDC Gene

mRNA expression in normal human tissues for PRKDC Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for PRKDC Gene

SOURCE GeneReport for Unigene cluster for PRKDC Gene Hs.491682

genes like me logo Genes that share expressions with PRKDC: view

Orthologs for PRKDC Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for PRKDC Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PRKDC 36
  • 99.61 (n)
  • 99.54 (a)
PRKDC 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia PRKDC 36
  • 78.87 (n)
  • 78.13 (a)
PRKDC 37
  • 78 (a)
OneToOne
dog
(Canis familiaris)
Mammalia PRKDC 36
  • 85.29 (n)
  • 83.26 (a)
PRKDC 37
  • 83 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Prkdc 36
  • 81.24 (n)
  • 79.37 (a)
Prkdc 16
Prkdc 37
  • 79 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia -- 37
  • 79 (a)
OneToMany
-- 37
  • 71 (a)
OneToMany
-- 37
  • 77 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 37
  • 75 (a)
OneToMany
-- 37
  • 79 (a)
OneToMany
-- 37
  • 80 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Prkdc 36
  • 81.02 (n)
  • 78.94 (a)
chicken
(Gallus gallus)
Aves PRKDC 36
  • 70.37 (n)
  • 69.13 (a)
PRKDC 37
  • 69 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PRKDC 37
  • 67 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia prkdc-A 36
tropical clawed frog
(Silurana tropicalis)
Amphibia prkdc 36
  • 66.03 (n)
  • 64.21 (a)
zebrafish
(Danio rerio)
Actinopterygii PRKDC 37
  • 58 (a)
OneToOne
wu:fa96e12 36
  • 61.39 (n)
  • 59.25 (a)
wufa96e12 36
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003967 36
  • 40.86 (n)
  • 28.25 (a)
fruit fly
(Drosophila melanogaster)
Insecta mei-41 37
  • 14 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea atl-1 37
  • 14 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MEC1 37
  • 15 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 39 (a)
OneToOne
Species with no ortholog for PRKDC:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for PRKDC Gene

ENSEMBL:
Gene Tree for PRKDC (if available)
TreeFam:
Gene Tree for PRKDC (if available)

Paralogs for PRKDC Gene

Paralogs for PRKDC Gene

genes like me logo Genes that share paralogs with PRKDC: view

Variants for PRKDC Gene

Sequence variations from dbSNP and Humsavar for PRKDC Gene

SNP ID Clin Chr 08 pos Sequence Context AA Info Type MAF
rs1231200 -- 47,944,459(-) TAGGT(A/G)TTGAA intron-variant
rs1231201 -- 47,933,603(+) ACACA(A/T)ATATA intron-variant
rs1231202 -- 47,933,959(+) GTAAA(C/T)GTTAC intron-variant
rs1231203 -- 47,954,228(+) AAAAG(G/T)ATTCG intron-variant
rs1231204 -- 47,954,713(+) GTTAC(C/G)TTCCC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for PRKDC Gene

Variant ID Type Subtype PubMed ID
dgv2234e1 CNV Complex 17122850
nsv6179 CNV Loss 18451855
nsv8337 CNV Gain 18304495
nsv831309 CNV Loss 17160897
esv2663658 CNV Deletion 23128226
nsv6180 CNV Insertion 18451855

Relevant External Links for PRKDC Gene

HapMap Linkage Disequilibrium report
PRKDC
Human Gene Mutation Database (HGMD)
PRKDC

Disorders for PRKDC Gene

UniProtKB/Swiss-Prot

PRKDC_HUMAN
  • Immunodeficiency 26 with or without neurologic abnormalities (IMD26) [MIM:615966]: 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. {ECO:0000269 PubMed:19075392, ECO:0000269 PubMed:23722905}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(4) University of Copenhagen DISEASES for PRKDC Gene

(7) Novoseek inferred disease relationships for PRKDC Gene

Disease -log(P) Hits PubMed IDs
ataxia telangiectasia 82.3 17
severe combined immunodeficiency 66.7 4
glioma 28.1 2
tumors 20.1 4
cancer 16.7 3

Relevant External Links for PRKDC

Genetic Association Database (GAD)
PRKDC
Human Genome Epidemiology (HuGE) Navigator
PRKDC
genes like me logo Genes that share disorders with PRKDC: view

Publications for PRKDC Gene

  1. Gene for the catalytic subunit of the human DNA-activated protein kinase maps to the site of the XRCC7 gene on chromosome 8. (PMID: 7638222) Sipley J.D. … Anderson C.W. (Proc. Natl. Acad. Sci. U.S.A. 1995) 2 3 4 23
  2. MCM4 and PRKDC, human genes encoding proteins MCM4 and DNA-PKcs, are close neighbours located on chromosome 8q12-->q13. (PMID: 9284934) Ladenburger E.M. … Knippers R. (Cytogenet. Cell Genet. 1997) 3 4 23
  3. Frameshift mutation in PRKDC, the gene for DNA-PKcs, in the DNA repair-defective, human, glioma-derived cell line M059J. (PMID: 11418067) Anderson C.W. … Allalunis-Turner M.J. (Radiat. Res. 2001) 3 4 23
  4. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. (PMID: 15758953) Falck J. … Jackson S.P. (Nature 2005) 3 4 23
  5. Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. (PMID: 12231622) Chan D.W. … Chen D.J. (Genes Dev. 2002) 3 4 23

Products for PRKDC Gene

Sources for PRKDC Gene

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