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UniProtKB/Swiss-Prot P78527 (PRKDC_HUMAN)
Last modified
February 9, 2010.
Version 112.
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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents
Names and origin
| Protein names | Recommended name: DNA-dependent protein kinase catalytic subunit Short name=DNA-PK catalytic subunit Short name=DNA-PKcs EC=2.7.11.1 Alternative name(s): DNPK1 p460 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 4128 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | 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, c-myc/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 TP53/p53 in the presence of supercoiled DNA is dependent on C1D. Ref.23 Ref.33 Ref.38 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Enzyme regulation | Inhibited by wortmannin. Activity of the enzyme seems to be attenuated by autophosphorylation. Ref.22 |
| Subunit structure | 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. Ref.23 Ref.38 Ref.24 Ref.29 Ref.36 Ref.37 Ref.39 Ref.43 Ref.44 Ref.45 |
| Subcellular location | |
| Post-translational modification | Phosphorylated upon DNA damage, probably by ATM or ATR. Autophosphorylated on Thr-2609, Thr-2638 and Thr-2647. Thr-2609 is a DNA damage-inducible phosphorylation site (inducible with ionizing radiation, IR). Autophosphorylation induces a conformational change that leads to remodeling of the DNA-PK complex, requisite for efficient end processing and DNA repair. Ref.31 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.18 Ref.20 Ref.21 Ref.26 Ref.27 Ref.28 Ref.30 Ref.32 Ref.34 Ref.35 Ref.40 Ref.41 Ref.42 Ref.46 Ref.47 Ref.49 Ref.50 Ref.51 Ref.52 Ref.53 Ref.57 |
| Sequence similarities | Belongs to the PI3/PI4-kinase family. Contains 1 FAT domain. Contains 1 FATC domain. Contains 2 HEAT repeats. Contains 1 PI3K/PI4K domain. Contains 3 TPR repeats. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| CASP2 | P42575 | 2 | EBI-352053,EBI-520342 | |
| HOXB7 | P09629 | 1 | EBI-352053,EBI-1248457 | |
| LRDD | Q9HB75 | 5 | EBI-352053,EBI-520427 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P78527-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: P78527-2) The sequence of this isoform differs from the canonical sequence as follows: 3799-3829: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed | ||||||
| Chain | 2 – 4128 | 4127 | DNA-dependent protein kinase catalytic subunit | PRO_0000225598 | |||||
Regions | |||||||||
| Repeat | 288 – 323 | 36 | HEAT 1 | ||||||
| Repeat | 1004 – 1040 | 37 | HEAT 2 | ||||||
| Domain | 1503 – 1538 | 36 | Leucine-zipper | ||||||
| Repeat | 1723 – 1756 | 34 | TPR 1 | ||||||
| Domain | 2883 – 3539 | 657 | FAT | ||||||
| Repeat | 2920 – 2948 | 29 | TPR 2 | ||||||
| Repeat | 2949 – 2982 | 34 | TPR 3 | ||||||
| Domain | 3747 – 4015 | 269 | PI3K/PI4K | ||||||
| Domain | 4096 – 4128 | 33 | FATC | ||||||
| Region | 1503 – 1538 | 36 | Interaction with C1D | ||||||
| Region | 2436 – 3212 | 777 | KIP-binding | ||||||
Sites | |||||||||
| Site | 2020 – 2021 | 2 | Cleavage; by caspase-3 Probable | ||||||
Amino acid modifications | |||||||||
| Modified residue | 2 | 1 | N-acetylalanine Ref.55 | ||||||
| Modified residue | 117 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 254 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 511 | 1 | Phosphoserine | ||||||
| Modified residue | 828 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 832 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 841 | 1 | Phosphoserine | ||||||
| Modified residue | 893 | 1 | Phosphoserine Ref.53 | ||||||
| Modified residue | 1052 | 1 | Phosphoserine Ref.52 | ||||||
| Modified residue | 1057 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 1209 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 1970 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 2117 | 1 | Phosphoserine Ref.52 | ||||||
| Modified residue | 2259 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 2603 | 1 | Phosphothreonine Ref.49 | ||||||
| Modified residue | 2609 | 1 | Phosphothreonine; by autocatalysis Ref.31 Ref.28 Ref.49 | ||||||
| Modified residue | 2612 | 1 | Phosphoserine; by autocatalysis Ref.28 Ref.49 Ref.51 | ||||||
| Modified residue | 2638 | 1 | Phosphothreonine; by autocatalysis Ref.28 Ref.49 Ref.51 | ||||||
| Modified residue | 2647 | 1 | Phosphothreonine; by autocatalysis Ref.28 Ref.49 Ref.51 | ||||||
| Modified residue | 2649 | 1 | Phosphothreonine Ref.49 | ||||||
| Modified residue | 2671 | 1 | Phosphothreonine | ||||||
| Modified residue | 2672 | 1 | Phosphoserine | ||||||
| Modified residue | 2743 | 1 | Phosphotyrosine Ref.50 | ||||||
| Modified residue | 3205 | 1 | Phosphoserine Ref.41 Ref.46 Ref.52 Ref.53 Ref.57 | ||||||
| Modified residue | 3241 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 3260 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 3608 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 3621 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 3638 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 3642 | 1 | N6-acetyllysine Ref.58 | ||||||
| Modified residue | 4026 | 1 | Phosphoserine Ref.52 Ref.53 | ||||||
Natural variations | |||||||||
| Alternative sequence | 3799 – 3829 | 31 | Missing in isoform 2. | VSP_004708 | |||||
| Natural variant | 6 | 1 | A → S: dbSNP rs8177999. Ref.3 Ref.59 | VAR_019179 | |||||
| Natural variant | 263 | 1 | K → N in a lung adenocarcinoma sample; somatic mutation. Ref.59 | VAR_041602 | |||||
| Natural variant | 333 | 1 | M → I: dbSNP rs8178017. Ref.3 Ref.59 | VAR_019180 | |||||
| Natural variant | 420 | 1 | V → I: dbSNP rs55925466. Ref.59 | VAR_041603 | |||||
| Natural variant | 500 | 1 | G → S in a metastatic melanoma sample; somatic mutation. Ref.59 | VAR_041604 | |||||
| Natural variant | 605 | 1 | T → S: dbSNP rs8178033. Ref.3 Ref.59 | VAR_019181 | |||||
| Natural variant | 649 | 1 | F → L: dbSNP rs55811715. Ref.59 | VAR_041605 | |||||
| Natural variant | 680 | 1 | I → M: dbSNP rs8178040. Ref.3 | VAR_019182 | |||||
| Natural variant | 695 | 1 | P → S: dbSNP rs8178046. Ref.3 Ref.59 | VAR_019183 | |||||
| Natural variant | 1071 | 1 | N → S: dbSNP rs8178070. Ref.3 | VAR_019184 | |||||
| Natural variant | 1136 | 1 | R → H in a colorectal adenocarcinoma sample; somatic mutation. Ref.59 | VAR_041606 | |||||
| Natural variant | 1190 | 1 | L → V: dbSNP rs34598508. Ref.59 | VAR_041607 | |||||
| Natural variant | 1237 | 1 | A → T | VAR_041608 | |||||
| Natural variant | 1279 | 1 | L → F | VAR_041609 | |||||
| Natural variant | 1314 | 1 | G → V: dbSNP rs8178090. Ref.3 | VAR_019185 | |||||
| Natural variant | 1447 | 1 | R → M in a lung squamous cell carcinoma sample; somatic mutation. Ref.59 | VAR_041610 | |||||
| Natural variant | 1588 | 1 | D → V: dbSNP rs8178104. Ref.3 | VAR_019186 | |||||
| Natural variant | 1603 | 1 | Q → H: dbSNP rs8178106. Ref.3 | VAR_019187 | |||||
| Natural variant | 1619 | 1 | A → G: dbSNP rs56182356. Ref.59 | VAR_041611 | |||||
| Natural variant | 1680 | 1 | A → V in a metastatic melanoma sample; somatic mutation. dbSNP rs55735910. Ref.59 | VAR_041612 | |||||
| Natural variant | 2023 | 1 | S → P: dbSNP rs56042895. Ref.59 | VAR_041613 | |||||
| Natural variant | 2095 | 1 | A → V: dbSNP rs8178147. Ref.3 | VAR_019188 | |||||
| Natural variant | 2598 | 1 | R → Q: dbSNP rs55923149. Ref.59 | VAR_041614 | |||||
| Natural variant | 2702 | 1 | K → E: dbSNP rs8178178. Ref.3 | VAR_019189 | |||||
| Natural variant | 2810 | 1 | S → N in a metastatic melanoma sample; somatic mutation. Ref.59 | VAR_041615 | |||||
| Natural variant | 2899 | 1 | R → C: dbSNP rs4278157. Ref.3 Ref.59 | VAR_019190 | |||||
| Natural variant | 2941 | 1 | G → A in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.59 | VAR_041616 | |||||
| Natural variant | 3085 | 1 | E → D: dbSNP rs56135402. Ref.59 | VAR_041617 | |||||
| Natural variant | 3149 | 1 | G → D: dbSNP rs8178208. Ref.3 Ref.59 | VAR_019191 | |||||
| Natural variant | 3198 | 1 | T → S: dbSNP rs55793951. Ref.59 | VAR_041618 | |||||
| Natural variant | 3201 | 1 | P → S: dbSNP rs8178216. Ref.3 Ref.59 | VAR_019192 | |||||
| Natural variant | 3404 | 1 | G → E: dbSNP rs8178225. Ref.3 Ref.59 | VAR_019193 | |||||
| Natural variant | 3434 | 1 | I → T: dbSNP rs7830743. Ref.3 Ref.59 | VAR_019194 | |||||
| Natural variant | 3459 | 1 | N → S: dbSNP rs8178228. Ref.3 | VAR_019195 | |||||
| Natural variant | 3562 | 1 | L → M: dbSNP rs8178232. Ref.3 Ref.59 | VAR_019196 | |||||
| Natural variant | 3584 | 1 | L → F | VAR_041619 | |||||
| Natural variant | 3702 | 1 | P → L: dbSNP rs8178236. | VAR_050534 | |||||
| Natural variant | 3800 | 1 | L → I | VAR_041620 | |||||
| Natural variant | 3836 | 1 | P → L: dbSNP rs8178245. Ref.3 Ref.59 | VAR_019197 | |||||
| Natural variant | 3932 | 1 | M → V | VAR_019198 | |||||
| Natural variant | 3936 | 1 | G → S | VAR_041621 | |||||
| Natural variant | 3937 | 1 | V → M | VAR_041622 | |||||
Experimental info | |||||||||
| Mutagenesis | 1510 | 1 | L → P: Loss of interaction with C1D. Ref.23 | ||||||
| Mutagenesis | 1516 – 1517 | 2 | EL → PD: Loss of interaction with C1D. | ||||||
| Mutagenesis | 2609 | 1 | T → A: Leads to radiation sensitivity and impaired DSB joining. Gives rise to reduced phosphorylation; when associated with A-2612. Ref.31 | ||||||
| Mutagenesis | 2612 | 1 | S → A: Reduced phosphorylation; when associated with A-2609. | ||||||
| Mutagenesis | 2638 | 1 | T → A: Alleviates phosphorylation, leaves a fully active enzyme with compromised cellular resistance to ionizing radiation without affecting DNA end joining; when associated with A-2647. Ref.33 | ||||||
| Mutagenesis | 2647 | 1 | T → A: Alleviates phosphorylation, leaves a fully active enzyme with compromised cellular resistance to ionizing radiation without affecting DNA end joining; when associated with A-2638. Ref.33 | ||||||
| Sequence conflict | 405 | 1 | D → Y in AAC50210. Ref.2 | ||||||
| Sequence conflict | 1008 | 1 | A → S in AAC50210. Ref.2 | ||||||
| Sequence conflict | 3660 | 1 | N → T Ref.8 | ||||||
| Sequence conflict | 3817 | 1 | L → W Ref.8 | ||||||
| Sequence conflict | 3862 | 1 | A → P Ref.8 | ||||||
| Sequence conflict | 4031 | 1 | I → V Ref.9 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product." Hartley K.O., Gell D., Smith G.C.M., Zhang H., Divecha N., Connelly M.A., Admon A., Lees-Miller S.P., Anderson C.W., Jackson S.P. Cell 82:849-856(1995) [PubMed: 7671312] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cervix carcinoma. |
| [2] | Gell D., Anderson C.W. Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION, ALTERNATIVE SPLICING. |
| [3] | NIEHS SNPs program Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-6; ILE-333; SER-605; MET-680; SER-695; SER-1071; VAL-1314; VAL-1588; HIS-1603; VAL-2095; GLU-2702; CYS-2899; ASP-3149; SER-3201; GLU-3404; THR-3434; SER-3459; MET-3562; LEU-3836 AND VAL-3932. |
| [4] | "Frameshift mutation in PRKDC, the gene for DNA-PKcs, in the DNA repair-defective, human, glioma-derived cell line M059J." Anderson C.W., Dunn J.J., Freimuth P.I., Galloway A.M., Allalunis-Turner M.J. Radiat. Res. 156:2-9(2001) [PubMed: 11418067] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-1689. |
| [5] | "MCM4 and PRKDC, human genes encoding proteins MCM4 and DNA-PKcs, are close neighbours located on chromosome 8q12-->q13." Ladenburger E.M., Fackelmayer F.O., Hameister H., Knippers R. Cytogenet. Cell Genet. 77:268-270(1997) [PubMed: 9284934] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-49. |
| [6] | "Gene for the catalytic subunit of the human DNA-activated protein kinase maps to the site of the XRCC7 gene on chromosome 8." Sipley J.D., Menninger J.C., Hartley K.O., Ward D.C., Jackson S.P., Anderson C.W. Proc. Natl. Acad. Sci. U.S.A. 92:7515-7519(1995) [PubMed: 7638222] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1789-2203. Tissue: Placenta. |
| [7] | Abe M. Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 2255-2335. Tissue: Placenta. |
| [8] | "Human DNA-activated protein kinase (DNA-PK) is homologous to phosphatidylinositol kinases." Poltoratsky V.P., Shi X., York J.D., Lieber M.R., Carter T.H. J. Immunol. 155:4529-4533(1995) [PubMed: 7594449] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3199-4128 (ISOFORM 1). Tissue: Fetal lung. |
| [9] | "Sequence of the 3' segment (exons 70-86) of PRKDC, the gene for human DNA-PKcs." Anderson C.W., Dunn J.J., Freimuth P.I. Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3250-4128 (ISOFORM 1). |
| [10] | Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno F.R. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3372-4128 (ISOFORM 2). Tissue: Brain. |
| [11] | "The human double-stranded DNA-activated protein kinase phosphorylates the 90-kDa heat-shock protein, hsp90 alpha at two NH2-terminal threonine residues." Lees-Miller S.P., Anderson C.W. J. Biol. Chem. 264:17275-17280(1989) [PubMed: 2507541] [Abstract] Cited for: PHOSPHORYLATION OF HSPCA. |
| [12] | "A DNA-activated protein kinase from HeLa cell nuclei." Carter T., Vancurova I., Sun I., Lou W., DeLeon S. Mol. Cell. Biol. 10:6460-6471(1990) [PubMed: 2247066] [Abstract] Cited for: PHOSPHORYLATION OF H1. |
| [13] | "DNA-activated protein kinase in Raji Burkitt's lymphoma cells. Phosphorylation of c-Myc oncoprotein." Iijima S., Teraoka H., Date T., Tsukada K. Eur. J. Biochem. 206:595-603(1992) [PubMed: 1597196] [Abstract] Cited for: PHOSPHORYLATION OF MYC. |
| [14] | "The carboxyl-terminal transactivation domain of human serum response factor contains DNA-activated protein kinase phosphorylation sites." Liu S.-H., Ma J.-T., Yueh A.Y., Lees-Miller S.P., Anderson C.W., Ng S.-Y. J. Biol. Chem. 268:21147-21154(1993) [PubMed: 8407951] [Abstract] Cited for: PHOSPHORYLATION OF SRF. |
| [15] | "c-Jun is phosphorylated by the DNA-dependent protein kinase in vitro; definition of the minimal kinase recognition motif." Bannister A.J., Gottlieb T.M., Kouzarides T., Jackson S.P. Nucleic Acids Res. 21:1289-1295(1993) [PubMed: 8464713] [Abstract] Cited for: PHOSPHORYLATION OF JUN. |
| [16] | "CPP32/Yama/apopain cleaves the catalytic component of DNA-dependent protein kinase in the holoenzyme." Teraoka H., Yumoto Y., Watanabe F., Tsukada K., Suwa A., Enari M., Nagata S. FEBS Lett. 393:1-6(1996) [PubMed: 8804412] [Abstract] Cited for: CLEAVAGE BY CASPASE-3. |
| [17] | "Alternate splice-site utilization in the gene for the catalytic subunit of the DNA-activated protein kinase, DNA-PKcs." Connelly M.A., Zhang H., Kieleczawa J., Anderson C.W. Gene 175:271-273(1996) [PubMed: 8917110] [Abstract] Cited for: ALTERNATIVE SPLICING. |
| [18] | "DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2." Shieh S.-Y., Ikeda M., Taya Y., Prives C. Cell 91:325-334(1997) [PubMed: 9363941] [Abstract] Cited for: PHOSPHORYLATION OF TP53. |
| [19] | "Interaction between DNA-dependent protein kinase and a novel protein, KIP." Wu X., Lieber M.R. Mutat. Res. 385:13-20(1997) [PubMed: 9372844] [Abstract] Cited for: CHARACTERIZATION. |
| [20] | "Double-strand break repair by Ku70 requires heterodimerization with Ku80 and DNA binding functions." Jin S., Weaver D.T. EMBO J. 16:6874-6885(1997) [PubMed: 9362500] [Abstract] Cited for: PHOSPHORYLATION OF XRCC6. |
| [21] | "Mapping of amino acid residues in the p34 subunit of human single-stranded DNA-binding protein phosphorylated by DNA-dependent protein kinase and Cdc2 kinase in vitro." Niu H., Erdjument-Bromage H., Pan Z.-Q., Lee S.-H., Tempst P., Hurwitz J. J. Biol. Chem. 272:12634-12641(1997) [PubMed: 9139719] [Abstract] Cited for: PHOSPHORYLATION OF RFA2. |
| [22] | "Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin." Sarkaria J.N., Tibbetts R.S., Busby E.C., Kennedy A.P., Hill D.E., Abraham R.T. Cancer Res. 58:4375-4382(1998) [PubMed: 9766667] [Abstract] Cited for: ENZYME REGULATION. |
| [23] | "DNA end-independent activation of DNA-PK mediated via association with the DNA-binding protein C1D." Yavuzer U., Smith G.C.M., Bliss T., Werner D., Jackson S.P. Genes Dev. 12:2188-2199(1998) [PubMed: 9679063] [Abstract] Cited for: FUNCTION, INTERACTION WITH C1D, MUTAGENESIS OF LEU-1510 AND 1516-GLU-LEU-1517. |
| [24] | "DNA-dependent protein kinase interacts with antigen receptor response element binding proteins NF90 and NF45." Ting N.S.Y., Kao P.N., Chan D.W., Lintott L.G., Lees-Miller S.P. J. Biol. Chem. 273:2136-2145(1998) [PubMed: 9442054] [Abstract] Cited for: INTERACTION WITH ILF3. |
| [25] | "DNA-dependent protein kinase: DNA binding and activation in the absence of Ku." Hammarsten O., Chu G. Proc. Natl. Acad. Sci. U.S.A. 95:525-530(1998) [PubMed: 9435225] [Abstract] Cited for: DNA-BINDING. |
| [26] | "DNA-dependent protein kinase phosphorylation sites in Ku 70/80 heterodimer." Chan D.W., Ye R., Veillette C.J., Lees-Miller S.P. Biochemistry 38:1819-1828(1999) [PubMed: 10026262] [Abstract] Cited for: PHOSPHORYLATION OF XRCC5 AND XRCC6. |
| [27] | "Suppression of the poly(ADP-ribose) polymerase activity by DNA-dependent protein kinase in vitro." Ariumi Y., Masutani M., Copeland T.D., Mimori T., Sugimura T., Shimotohno K., Ueda K., Hatanaka M., Noda M. Oncogene 18:4616-4625(1999) [PubMed: 10467406] [Abstract] Cited for: PHOSPHORYLATION OF PARP1. |
| [28] | "Identification of in vitro and in vivo phosphorylation sites in the catalytic subunit of the DNA-dependent protein kinase." Douglas P., Sapkota G.P., Morrice N., Yu Y., Goodarzi A.A., Merkle D., Meek K., Alessi D.R., Lees-Miller S.P. Biochem. J. 368:243-251(2002) [PubMed: 12186630] [Abstract] Cited for: PHOSPHORYLATION AT THR-2609; SER-2612; THR-2638 AND THR-2647. |
| [29] | "Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination." Ma Y., Pannicke U., Schwarz K., Lieber M.R. Cell 108:781-794(2002) [PubMed: 11955432] [Abstract] Cited for: INTERACTION WITH DCLRE1C. |
| [30] | "Defining interactions between DNA-PK and ligase IV/XRCC4." Hsu H.-L., Yannone S.M., Chen D.J. DNA Repair 1:225-235(2002) [PubMed: 12509254] [Abstract] Cited for: PHOSPHORYLATION OF XRCC4. |
| [31] | "Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks." Chan D.W., Chen B.P., Prithivirajsingh S., Kurimasa A., Story M.D., Qin J., Chen D.J. Genes Dev. 16:2333-2338(2002) [PubMed: 12231622] [Abstract] Cited for: MASS SPECTROMETRY, PHOSPHORYLATION AT THR-2609, MUTAGENESIS OF THR-2609, SUBCELLULAR LOCATION. |
| [32] | "Werner protein is a target of DNA-dependent protein kinase in vivo and in vitro, and its catalytic activities are regulated by phosphorylation." Karmakar P., Piotrowski J., Brosh R.M. Jr., Sommers J.A., Miller S.P., Cheng W.H., Snowden C.M., Ramsden D.A., Bohr V.A. J. Biol. Chem. 277:18291-18302(2002) [PubMed: 11889123] [Abstract] Cited for: PHOSPHORYLATION OF WRN. |
| [33] | "Threonines 2638/2647 in DNA-PK are essential for cellular resistance to ionizing radiation." Soubeyrand S., Pope L., Pakuts B., Hache R.J. Cancer Res. 63:1198-1201(2003) [PubMed: 12649176] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF THR-2638 AND THR-2647. |
| [34] | "Down-regulation of histone H2B by DNA-dependent protein kinase in response to DNA damage through modulation of octamer transcription factor 1." Schild-Poulter C., Shih A., Yarymowich N.C., Hache R.J.G. Cancer Res. 63:7197-7205(2003) [PubMed: 14612514] [Abstract] Cited for: PHOSPHORYLATION OF POU2F1. |
| [35] | "DNA-PK is activated by nucleosomes and phosphorylates H2AX within the nucleosomes in an acetylation-dependent manner." Park E.-J., Chan D.W., Park J.-H., Oettinger M.A., Kwon J. Nucleic Acids Res. 31:6819-6827(2003) [PubMed: 14627815] [Abstract] Cited for: PHOSPHORYLATION OF H2AFX. |
| [36] | "Functional and biochemical dissection of the structure-specific nuclease ARTEMIS." Pannicke U., Ma Y., Hopfner K.-P., Niewolik D., Lieber M.R., Schwarz K. EMBO J. 23:1987-1997(2004) [PubMed: 15071507] [Abstract] Cited for: INTERACTION WITH DCLRE1C. |
| [37] | "The metallo-beta-lactamase/beta-CASP domain of Artemis constitutes the catalytic core for V(D)J recombination." Poinsignon C., Moshous D., Callebaut I., de Chasseval R., Villey I., de Villartay J.-P. J. Exp. Med. 199:315-321(2004) [PubMed: 14744996] [Abstract] Cited for: INTERACTION WITH DCLRE1C. |
| [38] | "A biochemically defined system for mammalian nonhomologous DNA end joining." Ma Y., Lu H., Tippin B., Goodman M.F., Shimazaki N., Koiwai O., Hsieh C.-L., Schwarz K., Lieber M.R. Mol. Cell 16:701-713(2004) [PubMed: 15574326] [Abstract] Cited for: FUNCTION, INTERACTION WITH DCLRE1C. |
| [39] | "Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response." Zhang X., Succi J., Feng Z., Prithivirajsingh S., Story M.D., Legerski R.J. Mol. Cell. Biol. 24:9207-9220(2004) [PubMed: 15456891] [Abstract] Cited for: INTERACTION WITH DCLRE1C. |
| [40] | "DNA-dependent protein kinase (DNA-PK) phosphorylates nuclear DNA helicase II/RNA helicase A and hnRNP proteins in an RNA-dependent manner." Zhang S., Schlott B., Goerlach M., Grosse F. Nucleic Acids Res. 32:1-10(2004) [PubMed: 14704337] [Abstract] Cited for: PHOSPHORYLATION OF DHX9. |
| [41] | "Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3205, MASS SPECTROMETRY. Tissue: Epithelium. |
| [42] | "DNA-PK is responsible for enhanced phosphorylation of histone H2AX under hypertonic conditions." Reitsema T., Klokov D., Banath J.P., Olive P.L. DNA Repair 4:1172-1181(2005) [PubMed: 16046194] [Abstract] Cited for: PHOSPHORYLATION OF H2AFX. |
| [43] | "Artemis deficiency confers a DNA double-strand break repair defect and Artemis phosphorylation status is altered by DNA damage and cell cycle progression." Wang J., Pluth J.M., Cooper P.K., Cowan M.J., Chen D.J., Yannone S.M. DNA Repair 4:556-570(2005) [PubMed: 15811628] [Abstract] Cited for: INTERACTION WITH DCLRE1C. |
| [44] | "The Artemis:DNA-PKcs endonuclease cleaves DNA loops, flaps, and gaps." Ma Y., Schwarz K., Lieber M.R. DNA Repair 4:845-851(2005) [PubMed: 15936993] [Abstract] Cited for: INTERACTION WITH DCLRE1C. |
| [45] | "Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage." Falck J., Coates J., Jackson S.P. Nature 434:605-611(2005) [PubMed: 15758953] [Abstract] Cited for: INTERACTION WITH XRCC5. |
| [46] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3205, MASS SPECTROMETRY. Tissue: Epithelium. |
| [47] | "XRCC1 is phosphorylated by DNA-dependent protein kinase in response to DNA damage." Levy N., Martz A., Bresson A., Spenlehauer C., de Murcia G., Menissier-de Murcia J. Nucleic Acids Res. 34:32-41(2006) [PubMed: 16397295] [Abstract] Cited for: PHOSPHORYLATION OF XRCC1. |
| [48] | "The life and death of DNA-PK." Collis S.J., DeWeese T.L., Jeggo P.A., Parker A.R. Oncogene 24:949-961(2005) [PubMed: 15592499] [Abstract] Cited for: REVIEW. |
| [49] | "Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2603; THR-2609; SER-2612; THR-2638; THR-2647 AND THR-2649, MASS SPECTROMETRY. Tissue: Epithelium. |
| [50] | "Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M.  Comb M.J.Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-2743, MASS SPECTROMETRY. |
| [51] | "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2612; THR-2638 AND THR-2647, MASS SPECTROMETRY. |
| [52] | "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1052; SER-2117; SER-3205 AND SER-4026, MASS SPECTROMETRY. |
| [53] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-893; SER-3205 AND SER-4026, MASS SPECTROMETRY. |
| [54] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [55] | "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. |
| [56] | "Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-511; SER-841; SER-893; SER-2612; THR-2671; SER-2672; SER-3205 AND SER-4026, MASS SPECTROMETRY. |
| [57] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3205, MASS SPECTROMETRY. Tissue: T-cell. |
| [58] | "Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-117; LYS-254; LYS-828; LYS-832; LYS-1057; LYS-1209; LYS-1970; LYS-2259; LYS-3241; LYS-3260; LYS-3608; LYS-3621; LYS-3638 AND LYS-3642, MASS SPECTROMETRY. |
| [59] | "Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-6; ASN-263; ILE-333; ILE-420; SER-500; SER-605; LEU-649; SER-695; HIS-1136; VAL-1190; THR-1237; PHE-1279; MET-1447; GLY-1619; VAL-1680; VAL-1680; PRO-2023; GLN-2598; ASN-2810; CYS-2899; ALA-2941; ASP-3085; ASP-3149; SER-3198; SER-3201; GLU-3404; THR-3434; MET-3562; PHE-3584; ILE-3800; LEU-3836; SER-3936 AND MET-3937. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | U47077 mRNA. Translation: AAB39925.5. U34994 mRNA. Translation: AAC50210.3. AY316117 Genomic DNA. Translation: AAP69525.1. U63630 Genomic DNA. Translation: AAC52019.2. U90415 Genomic DNA. Translation: AAB51722.1. L27425 Genomic DNA. Translation: AAA79244.1. AB052953 Genomic DNA. Translation: BAB79635.1. U35835 mRNA. Translation: AAA79184.1. AY030284 Genomic DNA. Translation: AAK40350.1. AB208860 mRNA. Translation: BAD92097.1. |
| IPI | IPI00296337. IPI00376215. |
| PIR | A57099. G02083. |
| RefSeq | NP_001075109.1. NP_008835.5. |
| UniGene | Hs.491682 |
3D structure databases | |
| SMR | P78527. Positions 3716-4006. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-24186N. |
| IntAct | P78527. 38 interactions. |
| STRING | P78527. |
PTM databases | |
| PhosphoSite | P78527. |
2-D gel databases | |
| SWISS-2DPAGE | P78527. |
Proteomic databases | |
| PRIDE | P78527. |
Genome annotation databases | |
| Ensembl | ENST00000314191; ENSP00000313420; ENSG00000121031; Homo sapiens. [Genome view] |
| GeneID | 5591. |
| KEGG | hsa:5591. |
Organism-specific databases | |
| CTD | 5591. |
| GeneCards | GC08M048848. GC08M048849. |
| H-InvDB | HIX0017562. |
| HGNC | HGNC:9413. PRKDC. |
| HPA | CAB005167. |
| MIM | 600899. gene. |
| PharmGKB | PA33776. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG10627. |
| HOVERGEN | P78527. |
| InParanoid | P78527. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.1. 247. |
| Pathway_Interaction_DB | bard1pathway. BARD1 signaling events. pi3kciaktpathway. Class I PI3K signaling events mediated by Akt. ar_pathway. Coregulation of Androgen receptor activity. faspathway. FAS signaling pathway (CD95). |
| Reactome | REACT_216. DNA Repair. |
Gene expression databases | |
| ArrayExpress | P78527. |
| Bgee | P78527. |
| Genevestigator | P78527. |
| GermOnline | ENSG00000121031. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR016024. ARM-type_fold. IPR003152. FATC. IPR011009. Kinase-like_dom. IPR012582. NUC194. IPR000403. PI3/4_kinase_cat. IPR018936. PI3/4_kinase_CS. IPR003151. PIK-rel_kinase_FAT. IPR014009. PIK_FAT. [Graphical view] |
| Gene3D | G3DSA:1.10.1070.11. PI3/4_kinase_cat. 1 hit. |
| Pfam | PF02259. FAT. 1 hit. PF02260. FATC. 1 hit. PF08163. NUC194. 1 hit. PF00454. PI3_PI4_kinase. 1 hit. [Graphical view] |
| SMART | SM00146. PI3Kc. 1 hit. [Graphical view] |
| PROSITE | PS51189. FAT. 1 hit. PS51190. FATC. 1 hit. PS50077. HEAT_REPEAT. False negative. PS00915. PI3_4_KINASE_1. 1 hit. PS00916. PI3_4_KINASE_2. 1 hit. PS50290. PI3_4_KINASE_3. 1 hit. PS50005. TPR. False negative. PS50293. TPR_REGION. False negative. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 21692. |
| SOURCE | Search... |
Entry information
| Entry name | PRKDC_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P78527 Secondary accession number(s): P78528 Q9UME3 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 8 Human chromosome 8: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |
