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P78527

- PRKDC_HUMAN

UniProt

P78527 - PRKDC_HUMAN

Protein

DNA-dependent protein kinase catalytic subunit

Gene

PRKDC

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 160 (01 Oct 2014)
      Sequence version 3 (31 Oct 2003)
      Previous versions | rss
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    Functioni

    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.4 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    Inhibited by wortmannin. Activity of the enzyme seems to be attenuated by autophosphorylation.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei2020 – 20212Cleavage; by caspase-3Curated

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. DNA binding Source: UniProtKB-KW
    3. DNA-dependent protein kinase activity Source: MGI
    4. poly(A) RNA binding Source: UniProtKB
    5. protein binding Source: UniProtKB
    6. protein kinase activity Source: ProtInc
    7. protein serine/threonine kinase activity Source: BHF-UCL
    8. transcription factor binding Source: BHF-UCL

    GO - Biological processi

    1. B cell lineage commitment Source: Ensembl
    2. brain development Source: Ensembl
    3. cellular protein modification process Source: ProtInc
    4. cellular response to insulin stimulus Source: BHF-UCL
    5. DNA repair Source: Reactome
    6. double-strand break repair Source: Reactome
    7. double-strand break repair via nonhomologous end joining Source: Reactome
    8. ectopic germ cell programmed cell death Source: Ensembl
    9. heart development Source: Ensembl
    10. immunoglobulin V(D)J recombination Source: Ensembl
    11. innate immune response Source: Reactome
    12. intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
    13. negative regulation of protein phosphorylation Source: UniProtKB
    14. peptidyl-serine phosphorylation Source: BHF-UCL
    15. positive regulation of apoptotic process Source: Ensembl
    16. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    17. positive regulation of type I interferon production Source: Reactome
    18. pro-B cell differentiation Source: Ensembl
    19. protein destabilization Source: Ensembl
    20. regulation of circadian rhythm Source: UniProtKB
    21. response to gamma radiation Source: Ensembl
    22. rhythmic process Source: UniProtKB-KW
    23. signal transduction involved in mitotic G1 DNA damage checkpoint Source: UniProtKB
    24. somitogenesis Source: Ensembl
    25. T cell differentiation in thymus Source: Ensembl
    26. T cell lineage commitment Source: Ensembl
    27. T cell receptor V(D)J recombination Source: Ensembl
    28. telomere maintenance Source: Ensembl

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Biological rhythms, DNA damage, DNA recombination, DNA repair

    Keywords - Ligandi

    ATP-binding, DNA-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_1022. Nonhomologous End-joining (NHEJ).
    REACT_1201. Processing of DNA ends prior to end rejoining.
    REACT_163993. IRF3-mediated induction of type I IFN.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    DNA-dependent protein kinase catalytic subunit (EC:2.7.11.1)
    Short name:
    DNA-PK catalytic subunit
    Short name:
    DNA-PKcs
    Alternative name(s):
    DNPK1
    p460
    Gene namesi
    Name:PRKDC
    Synonyms:HYRC, HYRC1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:9413. PRKDC.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. DNA-dependent protein kinase-DNA ligase 4 complex Source: MGI
    3. membrane Source: UniProtKB
    4. nonhomologous end joining complex Source: UniProtKB
    5. nucleolus Source: UniProtKB-SubCell
    6. nucleoplasm Source: Reactome
    7. nucleus Source: HPA
    8. transcription factor complex Source: BHF-UCL

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi1510 – 15101L → P: Loss of interaction with C1D. 1 Publication
    Mutagenesisi1516 – 15172EL → PD: Loss of interaction with C1D.
    Mutagenesisi2609 – 26091T → A: Leads to radiation sensitivity and impaired DSB joining. Gives rise to reduced phosphorylation; when associated with A-2612. 1 Publication
    Mutagenesisi2612 – 26121S → A: Reduced phosphorylation; when associated with A-2609.
    Mutagenesisi2638 – 26381T → 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. 1 Publication
    Mutagenesisi2647 – 26471T → 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. 1 Publication

    Organism-specific databases

    Orphaneti317425. Severe combined immunodeficiency due to DNA-PKcs deficiency.
    PharmGKBiPA33776.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 41284128DNA-dependent protein kinase catalytic subunitPRO_0000225598Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei117 – 1171N6-acetyllysine1 Publication
    Modified residuei828 – 8281N6-acetyllysine1 Publication
    Modified residuei893 – 8931Phosphoserine1 Publication
    Modified residuei1209 – 12091N6-acetyllysine1 Publication
    Modified residuei1970 – 19701N6-acetyllysine1 Publication
    Modified residuei2056 – 20561Phosphoserine; by autocatalysis1 Publication
    Modified residuei2259 – 22591N6-acetyllysine1 Publication
    Modified residuei2609 – 26091Phosphothreonine; by autocatalysis3 Publications
    Modified residuei2612 – 26121Phosphoserine; by autocatalysis3 Publications
    Modified residuei2638 – 26381Phosphothreonine; by autocatalysis1 Publication
    Modified residuei2647 – 26471Phosphothreonine; by autocatalysis1 Publication
    Modified residuei3205 – 32051Phosphoserine7 Publications
    Modified residuei3241 – 32411N6-acetyllysine1 Publication
    Modified residuei3260 – 32601N6-acetyllysine1 Publication
    Modified residuei3621 – 36211N6-acetyllysine1 Publication
    Modified residuei3638 – 36381N6-acetyllysine1 Publication
    Modified residuei3642 – 36421N6-acetyllysine1 Publication
    Modified residuei4026 – 40261Phosphoserine3 Publications

    Post-translational modificationi

    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.28 Publications
    S-nitrosylated by GAPDH.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP78527.
    PaxDbiP78527.
    PRIDEiP78527.

    2D gel databases

    SWISS-2DPAGEP78527.

    PTM databases

    PhosphoSiteiP78527.

    Expressioni

    Gene expression databases

    ArrayExpressiP78527.
    BgeeiP78527.
    GenevestigatoriP78527.

    Organism-specific databases

    HPAiCAB005167.
    HPA035174.

    Interactioni

    Subunit structurei

    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 CIB1.14 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    AIREO439182EBI-352053,EBI-1753081
    CASP2P425754EBI-352053,EBI-520342
    ETS1P149212EBI-352053,EBI-913209
    ETV1P505492EBI-352053,EBI-3905068
    HOXB7P096292EBI-352053,EBI-1248457
    IGFBP3P179362EBI-352053,EBI-715709
    MAPKAP1Q9BPZ72EBI-352053,EBI-749938
    PIDD1Q9HB756EBI-352053,EBI-520427
    SPI1P179472EBI-352053,EBI-2293548
    XRCC5P130106EBI-352053,EBI-357997
    XRCC6P129565EBI-352053,EBI-353208
    YY1P254902EBI-352053,EBI-765538

    Protein-protein interaction databases

    BioGridi111577. 212 interactions.
    DIPiDIP-24186N.
    IntActiP78527. 70 interactions.
    MINTiMINT-5006046.

    Structurei

    3D structure databases

    ProteinModelPortaliP78527.
    SMRiP78527. Positions 3724-3998.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati288 – 32336HEAT 1Add
    BLAST
    Repeati1004 – 104037HEAT 2Add
    BLAST
    Repeati1723 – 175634TPR 1Add
    BLAST
    Domaini2883 – 3539657FATPROSITE-ProRule annotationAdd
    BLAST
    Repeati2920 – 294829TPR 2Add
    BLAST
    Repeati2949 – 298234TPR 3Add
    BLAST
    Domaini3747 – 4015269PI3K/PI4KPROSITE-ProRule annotationAdd
    BLAST
    Domaini4096 – 412833FATCPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1503 – 153836Interaction with C1DAdd
    BLAST
    Regioni1503 – 153836Leucine-zipperAdd
    BLAST
    Regioni2436 – 3212777KIP-bindingAdd
    BLAST

    Sequence similaritiesi

    Belongs to the PI3/PI4-kinase family.Curated
    Contains 1 FAT domain.PROSITE-ProRule annotation
    Contains 1 FATC domain.PROSITE-ProRule annotation
    Contains 2 HEAT repeats.Curated
    Contains 1 PI3K/PI4K domain.PROSITE-ProRule annotation
    Contains 3 TPR repeats.Curated

    Keywords - Domaini

    Repeat, TPR repeat

    Phylogenomic databases

    eggNOGiCOG5032.
    HOVERGENiHBG053681.
    InParanoidiP78527.
    KOiK06642.
    OrthoDBiEOG7DNNT7.
    PhylomeDBiP78527.
    TreeFamiTF324494.

    Family and domain databases

    Gene3Di1.10.1070.11. 3 hits.
    1.25.10.10. 3 hits.
    InterProiIPR011989. ARM-like.
    IPR016024. ARM-type_fold.
    IPR003152. FATC.
    IPR011009. Kinase-like_dom.
    IPR012582. NUC194.
    IPR000403. PI3/4_kinase_cat_dom.
    IPR018936. PI3/4_kinase_CS.
    IPR003151. PIK-rel_kinase_FAT.
    IPR014009. PIK_FAT.
    [Graphical view]
    PfamiPF02259. FAT. 1 hit.
    PF02260. FATC. 1 hit.
    PF08163. NUC194. 1 hit.
    PF00454. PI3_PI4_kinase. 1 hit.
    [Graphical view]
    SMARTiSM00146. PI3Kc. 1 hit.
    [Graphical view]
    SUPFAMiSSF48371. SSF48371. 8 hits.
    SSF56112. SSF56112. 2 hits.
    PROSITEiPS51189. FAT. 1 hit.
    PS51190. FATC. 1 hit.
    PS00915. PI3_4_KINASE_1. 1 hit.
    PS00916. PI3_4_KINASE_2. 1 hit.
    PS50290. PI3_4_KINASE_3. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P78527-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MAGSGAGVRC SLLRLQETLS AADRCGAALA GHQLIRGLGQ ECVLSSSPAV     50
    LALQTSLVFS RDFGLLVFVR KSLNSIEFRE CREEILKFLC IFLEKMGQKI 100
    APYSVEIKNT CTSVYTKDRA AKCKIPALDL LIKLLQTFRS SRLMDEFKIG 150
    ELFSKFYGEL ALKKKIPDTV LEKVYELLGL LGEVHPSEMI NNAENLFRAF 200
    LGELKTQMTS AVREPKLPVL AGCLKGLSSL LCNFTKSMEE DPQTSREIFN 250
    FVLKAIRPQI DLKRYAVPSA GLRLFALHAS QFSTCLLDNY VSLFEVLLKW 300
    CAHTNVELKK AALSALESFL KQVSNMVAKN AEMHKNKLQY FMEQFYGIIR 350
    NVDSNNKELS IAIRGYGLFA GPCKVINAKD VDFMYVELIQ RCKQMFLTQT 400
    DTGDDRVYQM PSFLQSVASV LLYLDTVPEV YTPVLEHLVV MQIDSFPQYS 450
    PKMQLVCCRA IVKVFLALAA KGPVLRNCIS TVVHQGLIRI CSKPVVLPKG 500
    PESESEDHRA SGEVRTGKWK VPTYKDYVDL FRHLLSSDQM MDSILADEAF 550
    FSVNSSSESL NHLLYDEFVK SVLKIVEKLD LTLEIQTVGE QENGDEAPGV 600
    WMIPTSDPAA NLHPAKPKDF SAFINLVEFC REILPEKQAE FFEPWVYSFS 650
    YELILQSTRL PLISGFYKLL SITVRNAKKI KYFEGVSPKS LKHSPEDPEK 700
    YSCFALFVKF GKEVAVKMKQ YKDELLASCL TFLLSLPHNI IELDVRAYVP 750
    ALQMAFKLGL SYTPLAEVGL NALEEWSIYI DRHVMQPYYK DILPCLDGYL 800
    KTSALSDETK NNWEVSALSR AAQKGFNKVV LKHLKKTKNL SSNEAISLEE 850
    IRIRVVQMLG SLGGQINKNL LTVTSSDEMM KSYVAWDREK RLSFAVPFRE 900
    MKPVIFLDVF LPRVTELALT ASDRQTKVAA CELLHSMVMF MLGKATQMPE 950
    GGQGAPPMYQ LYKRTFPVLL RLACDVDQVT RQLYEPLVMQ LIHWFTNNKK 1000
    FESQDTVALL EAILDGIVDP VDSTLRDFCG RCIREFLKWS IKQITPQQQE 1050
    KSPVNTKSLF KRLYSLALHP NAFKRLGASL AFNNIYREFR EEESLVEQFV 1100
    FEALVIYMES LALAHADEKS LGTIQQCCDA IDHLCRIIEK KHVSLNKAKK 1150
    RRLPRGFPPS ASLCLLDLVK WLLAHCGRPQ TECRHKSIEL FYKFVPLLPG 1200
    NRSPNLWLKD VLKEEGVSFL INTFEGGGCG QPSGILAQPT LLYLRGPFSL 1250
    QATLCWLDLL LAALECYNTF IGERTVGALQ VLGTEAQSSL LKAVAFFLES 1300
    IAMHDIIAAE KCFGTGAAGN RTSPQEGERY NYSKCTVVVR IMEFTTTLLN 1350
    TSPEGWKLLK KDLCNTHLMR VLVQTLCEPA SIGFNIGDVQ VMAHLPDVCV 1400
    NLMKALKMSP YKDILETHLR EKITAQSIEE LCAVNLYGPD AQVDRSRLAA 1450
    VVSACKQLHR AGLLHNILPS QSTDLHHSVG TELLSLVYKG IAPGDERQCL 1500
    PSLDLSCKQL ASGLLELAFA FGGLCERLVS LLLNPAVLST ASLGSSQGSV 1550
    IHFSHGEYFY SLFSETINTE LLKNLDLAVL ELMQSSVDNT KMVSAVLNGM 1600
    LDQSFRERAN QKHQGLKLAT TILQHWKKCD SWWAKDSPLE TKMAVLALLA 1650
    KILQIDSSVS FNTSHGSFPE VFTTYISLLA DTKLDLHLKG QAVTLLPFFT 1700
    SLTGGSLEEL RRVLEQLIVA HFPMQSREFP PGTPRFNNYV DCMKKFLDAL 1750
    ELSQSPMLLE LMTEVLCREQ QHVMEELFQS SFRRIARRGS CVTQVGLLES 1800
    VYEMFRKDDP RLSFTRQSFV DRSLLTLLWH CSLDALREFF STIVVDAIDV 1850
    LKSRFTKLNE STFDTQITKK MGYYKILDVM YSRLPKDDVH AKESKINQVF 1900
    HGSCITEGNE LTKTLIKLCY DAFTENMAGE NQLLERRRLY HCAAYNCAIS 1950
    VICCVFNELK FYQGFLFSEK PEKNLLIFEN LIDLKRRYNF PVEVEVPMER 2000
    KKKYIEIRKE AREAANGDSD GPSYMSSLSY LADSTLSEEM SQFDFSTGVQ 2050
    SYSYSSQDPR PATGRFRRRE QRDPTVHDDV LELEMDELNR HECMAPLTAL 2100
    VKHMHRSLGP PQGEEDSVPR DLPSWMKFLH GKLGNPIVPL NIRLFLAKLV 2150
    INTEEVFRPY AKHWLSPLLQ LAASENNGGE GIHYMVVEIV ATILSWTGLA 2200
    TPTGVPKDEV LANRLLNFLM KHVFHPKRAV FRHNLEIIKT LVECWKDCLS 2250
    IPYRLIFEKF SGKDPNSKDN SVGIQLLGIV MANDLPPYDP QCGIQSSEYF 2300
    QALVNNMSFV RYKEVYAAAA EVLGLILRYV MERKNILEES LCELVAKQLK 2350
    QHQNTMEDKF IVCLNKVTKS FPPLADRFMN AVFFLLPKFH GVLKTLCLEV 2400
    VLCRVEGMTE LYFQLKSKDF VQVMRHRDDE RQKVCLDIIY KMMPKLKPVE 2450
    LRELLNPVVE FVSHPSTTCR EQMYNILMWI HDNYRDPESE TDNDSQEIFK 2500
    LAKDVLIQGL IDENPGLQLI IRNFWSHETR LPSNTLDRLL ALNSLYSPKI 2550
    EVHFLSLATN FLLEMTSMSP DYPNPMFEHP LSECEFQEYT IDSDWRFRST 2600
    VLTPMFVETQ ASQGTLQTRT QEGSLSARWP VAGQIRATQQ QHDFTLTQTA 2650
    DGRSSFDWLT GSSTDPLVDH TSPSSDSLLF AHKRSERLQR APLKSVGPDF 2700
    GKKRLGLPGD EVDNKVKGAA GRTDLLRLRR RFMRDQEKLS LMYARKGVAE 2750
    QKREKEIKSE LKMKQDAQVV LYRSYRHGDL PDIQIKHSSL ITPLQAVAQR 2800
    DPIIAKQLFS SLFSGILKEM DKFKTLSEKN NITQKLLQDF NRFLNTTFSF 2850
    FPPFVSCIQD ISCQHAALLS LDPAAVSAGC LASLQQPVGI RLLEEALLRL 2900
    LPAELPAKRV RGKARLPPDV LRWVELAKLY RSIGEYDVLR GIFTSEIGTK 2950
    QITQSALLAE ARSDYSEAAK QYDEALNKQD WVDGEPTEAE KDFWELASLD 3000
    CYNHLAEWKS LEYCSTASID SENPPDLNKI WSEPFYQETY LPYMIRSKLK 3050
    LLLQGEADQS LLTFIDKAMH GELQKAILEL HYSQELSLLY LLQDDVDRAK 3100
    YYIQNGIQSF MQNYSSIDVL LHQSRLTKLQ SVQALTEIQE FISFISKQGN 3150
    LSSQVPLKRL LNTWTNRYPD AKMDPMNIWD DIITNRCFFL SKIEEKLTPL 3200
    PEDNSMNVDQ DGDPSDRMEV QEQEEDISSL IRSCKFSMKM KMIDSARKQN 3250
    NFSLAMKLLK ELHKESKTRD DWLVSWVQSY CRLSHCRSRS QGCSEQVLTV 3300
    LKTVSLLDEN NVSSYLSKNI LAFRDQNILL GTTYRIIANA LSSEPACLAE 3350
    IEEDKARRIL ELSGSSSEDS EKVIAGLYQR AFQHLSEAVQ AAEEEAQPPS 3400
    WSCGPAAGVI DAYMTLADFC DQQLRKEEEN ASVIDSAELQ AYPALVVEKM 3450
    LKALKLNSNE ARLKFPRLLQ IIERYPEETL SLMTKEISSV PCWQFISWIS 3500
    HMVALLDKDQ AVAVQHSVEE ITDNYPQAIV YPFIISSESY SFKDTSTGHK 3550
    NKEFVARIKS KLDQGGVIQD FINALDQLSN PELLFKDWSN DVRAELAKTP 3600
    VNKKNIEKMY ERMYAALGDP KAPGLGAFRR KFIQTFGKEF DKHFGKGGSK 3650
    LLRMKLSDFN DITNMLLLKM NKDSKPPGNL KECSPWMSDF KVEFLRNELE 3700
    IPGQYDGRGK PLPEYHVRIA GFDERVTVMA SLRRPKRIII RGHDEREHPF 3750
    LVKGGEDLRQ DQRVEQLFQV MNGILAQDSA CSQRALQLRT YSVVPMTSRL 3800
    GLIEWLENTV TLKDLLLNTM SQEEKAAYLS DPRAPPCEYK DWLTKMSGKH 3850
    DVGAYMLMYK GANRTETVTS FRKRESKVPA DLLKRAFVRM STSPEAFLAL 3900
    RSHFASSHAL ICISHWILGI GDRHLNNFMV AMETGGVIGI DFGHAFGSAT 3950
    QFLPVPELMP FRLTRQFINL MLPMKETGLM YSIMVHALRA FRSDPGLLTN 4000
    TMDVFVKEPS FDWKNFEQKM LKKGGSWIQE INVAEKNWYP RQKICYAKRK 4050
    LAGANPAVIT CDELLLGHEK APAFRDYVAV ARGSKDHNIR AQEPESGLSE 4100
    ETQVKCLMDQ ATDPNILGRT WEGWEPWM 4128
    Length:4,128
    Mass (Da):469,089
    Last modified:October 31, 2003 - v3
    Checksum:iAC6E747FEB09F3E5
    GO
    Isoform 2 (identifier: P78527-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         3799-3829: Missing.

    Show »
    Length:4,097
    Mass (Da):465,501
    Checksum:iB698F749065D319B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti405 – 4051D → Y in AAC50210. 1 PublicationCurated
    Sequence conflicti1008 – 10081A → S in AAC50210. 1 PublicationCurated
    Sequence conflicti3660 – 36601N → T in AAA79184. (PubMed:7594449)Curated
    Sequence conflicti3817 – 38171L → W in AAA79184. (PubMed:7594449)Curated
    Sequence conflicti3862 – 38621A → P in AAA79184. (PubMed:7594449)Curated
    Sequence conflicti4031 – 40311I → V in AAK40350. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti6 – 61A → S.2 Publications
    Corresponds to variant rs8177999 [ dbSNP | Ensembl ].
    VAR_019179
    Natural varianti263 – 2631K → N in a lung adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_041602
    Natural varianti333 – 3331M → I.2 Publications
    Corresponds to variant rs8178017 [ dbSNP | Ensembl ].
    VAR_019180
    Natural varianti420 – 4201V → I.1 Publication
    Corresponds to variant rs55925466 [ dbSNP | Ensembl ].
    VAR_041603
    Natural varianti500 – 5001G → S in a metastatic melanoma sample; somatic mutation. 1 Publication
    VAR_041604
    Natural varianti605 – 6051T → S.2 Publications
    Corresponds to variant rs8178033 [ dbSNP | Ensembl ].
    VAR_019181
    Natural varianti649 – 6491F → L.1 Publication
    Corresponds to variant rs55811715 [ dbSNP | Ensembl ].
    VAR_041605
    Natural varianti680 – 6801I → M.1 Publication
    Corresponds to variant rs8178040 [ dbSNP | Ensembl ].
    VAR_019182
    Natural varianti695 – 6951P → S.2 Publications
    Corresponds to variant rs8178046 [ dbSNP | Ensembl ].
    VAR_019183
    Natural varianti1071 – 10711N → S.1 Publication
    Corresponds to variant rs8178070 [ dbSNP | Ensembl ].
    VAR_019184
    Natural varianti1136 – 11361R → H in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_041606
    Natural varianti1190 – 11901L → V.1 Publication
    Corresponds to variant rs34598508 [ dbSNP | Ensembl ].
    VAR_041607
    Natural varianti1237 – 12371A → T.1 Publication
    VAR_041608
    Natural varianti1279 – 12791L → F.1 Publication
    VAR_041609
    Natural varianti1314 – 13141G → V.1 Publication
    Corresponds to variant rs8178090 [ dbSNP | Ensembl ].
    VAR_019185
    Natural varianti1447 – 14471R → M in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication
    VAR_041610
    Natural varianti1588 – 15881D → V.1 Publication
    Corresponds to variant rs8178104 [ dbSNP | Ensembl ].
    VAR_019186
    Natural varianti1603 – 16031Q → H.1 Publication
    Corresponds to variant rs8178106 [ dbSNP | Ensembl ].
    VAR_019187
    Natural varianti1619 – 16191A → G.1 Publication
    Corresponds to variant rs56182356 [ dbSNP | Ensembl ].
    VAR_041611
    Natural varianti1680 – 16801A → V in a metastatic melanoma sample; somatic mutation. 1 Publication
    Corresponds to variant rs55735910 [ dbSNP | Ensembl ].
    VAR_041612
    Natural varianti2023 – 20231S → P.1 Publication
    Corresponds to variant rs56042895 [ dbSNP | Ensembl ].
    VAR_041613
    Natural varianti2095 – 20951A → V.1 Publication
    Corresponds to variant rs8178147 [ dbSNP | Ensembl ].
    VAR_019188
    Natural varianti2598 – 25981R → Q.1 Publication
    Corresponds to variant rs55923149 [ dbSNP | Ensembl ].
    VAR_041614
    Natural varianti2702 – 27021K → E.1 Publication
    Corresponds to variant rs8178178 [ dbSNP | Ensembl ].
    VAR_019189
    Natural varianti2810 – 28101S → N in a metastatic melanoma sample; somatic mutation. 1 Publication
    VAR_041615
    Natural varianti2899 – 28991R → C.2 Publications
    Corresponds to variant rs4278157 [ dbSNP | Ensembl ].
    VAR_019190
    Natural varianti2941 – 29411G → A in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication
    VAR_041616
    Natural varianti3085 – 30851E → D.1 Publication
    Corresponds to variant rs56135402 [ dbSNP | Ensembl ].
    VAR_041617
    Natural varianti3149 – 31491G → D.2 Publications
    Corresponds to variant rs8178208 [ dbSNP | Ensembl ].
    VAR_019191
    Natural varianti3198 – 31981T → S.1 Publication
    Corresponds to variant rs55793951 [ dbSNP | Ensembl ].
    VAR_041618
    Natural varianti3201 – 32011P → S.2 Publications
    Corresponds to variant rs8178216 [ dbSNP | Ensembl ].
    VAR_019192
    Natural varianti3404 – 34041G → E.2 Publications
    Corresponds to variant rs8178225 [ dbSNP | Ensembl ].
    VAR_019193
    Natural varianti3434 – 34341I → T.2 Publications
    Corresponds to variant rs7830743 [ dbSNP | Ensembl ].
    VAR_019194
    Natural varianti3459 – 34591N → S.1 Publication
    Corresponds to variant rs8178228 [ dbSNP | Ensembl ].
    VAR_019195
    Natural varianti3562 – 35621L → M.2 Publications
    Corresponds to variant rs8178232 [ dbSNP | Ensembl ].
    VAR_019196
    Natural varianti3584 – 35841L → F.1 Publication
    VAR_041619
    Natural varianti3702 – 37021P → L.
    Corresponds to variant rs8178236 [ dbSNP | Ensembl ].
    VAR_050534
    Natural varianti3800 – 38001L → I.1 Publication
    VAR_041620
    Natural varianti3836 – 38361P → L.2 Publications
    Corresponds to variant rs8178245 [ dbSNP | Ensembl ].
    VAR_019197
    Natural varianti3932 – 39321M → V.1 Publication
    VAR_019198
    Natural varianti3936 – 39361G → S.1 Publication
    VAR_041621
    Natural varianti3937 – 39371V → M.1 Publication
    VAR_041622

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei3799 – 382931Missing in isoform 2. 1 PublicationVSP_004708Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    PIRiA57099.
    G02083.
    RefSeqiNP_001075109.1. NM_001081640.1. [P78527-2]
    NP_008835.5. NM_006904.6. [P78527-1]
    UniGeneiHs.491682.

    Genome annotation databases

    EnsembliENST00000314191; ENSP00000313420; ENSG00000253729.
    GeneIDi5591.
    KEGGihsa:5591.
    UCSCiuc003xqi.3. human. [P78527-1]
    uc003xqj.3. human. [P78527-2]

    Polymorphism databases

    DMDMi38258929.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    PIRi A57099.
    G02083.
    RefSeqi NP_001075109.1. NM_001081640.1. [P78527-2 ]
    NP_008835.5. NM_006904.6. [P78527-1 ]
    UniGenei Hs.491682.

    3D structure databases

    ProteinModelPortali P78527.
    SMRi P78527. Positions 3724-3998.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111577. 212 interactions.
    DIPi DIP-24186N.
    IntActi P78527. 70 interactions.
    MINTi MINT-5006046.

    Chemistry

    BindingDBi P78527.
    ChEMBLi CHEMBL3142.

    PTM databases

    PhosphoSitei P78527.

    Polymorphism databases

    DMDMi 38258929.

    2D gel databases

    SWISS-2DPAGE P78527.

    Proteomic databases

    MaxQBi P78527.
    PaxDbi P78527.
    PRIDEi P78527.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000314191 ; ENSP00000313420 ; ENSG00000253729 .
    GeneIDi 5591.
    KEGGi hsa:5591.
    UCSCi uc003xqi.3. human. [P78527-1 ]
    uc003xqj.3. human. [P78527-2 ]

    Organism-specific databases

    CTDi 5591.
    GeneCardsi GC08M048685.
    HGNCi HGNC:9413. PRKDC.
    HPAi CAB005167.
    HPA035174.
    MIMi 600899. gene.
    neXtProti NX_P78527.
    Orphaneti 317425. Severe combined immunodeficiency due to DNA-PKcs deficiency.
    PharmGKBi PA33776.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5032.
    HOVERGENi HBG053681.
    InParanoidi P78527.
    KOi K06642.
    OrthoDBi EOG7DNNT7.
    PhylomeDBi P78527.
    TreeFami TF324494.

    Enzyme and pathway databases

    Reactomei REACT_1022. Nonhomologous End-joining (NHEJ).
    REACT_1201. Processing of DNA ends prior to end rejoining.
    REACT_163993. IRF3-mediated induction of type I IFN.

    Miscellaneous databases

    ChiTaRSi PRKDC. human.
    GeneWikii DNA-PKcs.
    GenomeRNAii 5591.
    NextBioi 21692.
    PROi P78527.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P78527.
    Bgeei P78527.
    Genevestigatori P78527.

    Family and domain databases

    Gene3Di 1.10.1070.11. 3 hits.
    1.25.10.10. 3 hits.
    InterProi IPR011989. ARM-like.
    IPR016024. ARM-type_fold.
    IPR003152. FATC.
    IPR011009. Kinase-like_dom.
    IPR012582. NUC194.
    IPR000403. PI3/4_kinase_cat_dom.
    IPR018936. PI3/4_kinase_CS.
    IPR003151. PIK-rel_kinase_FAT.
    IPR014009. PIK_FAT.
    [Graphical view ]
    Pfami PF02259. FAT. 1 hit.
    PF02260. FATC. 1 hit.
    PF08163. NUC194. 1 hit.
    PF00454. PI3_PI4_kinase. 1 hit.
    [Graphical view ]
    SMARTi SM00146. PI3Kc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48371. SSF48371. 8 hits.
    SSF56112. SSF56112. 2 hits.
    PROSITEi PS51189. FAT. 1 hit.
    PS51190. FATC. 1 hit.
    PS00915. PI3_4_KINASE_1. 1 hit.
    PS00916. PI3_4_KINASE_2. 1 hit.
    PS50290. PI3_4_KINASE_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION, INTERACTION WITH CIB1.
    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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-2609, MUTAGENESIS OF THR-2609, SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY.
    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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION OF DHX9.
    41. Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-2056 AND THR-2609, DEPHOSPHORYLATION AT SER-2056 AND THR-2609.
    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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3205, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    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] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION OF XRCC1.
    48. Cited for: REVIEW.
    49. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic kidney.
    50. "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] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3205 AND SER-4026, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    51. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3205, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    52. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-893; SER-2612; SER-3205 AND SER-4026, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    53. "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] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3205, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    54. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
      Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
      Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-117; LYS-828; LYS-1209; LYS-1970; LYS-2259; LYS-3241; LYS-3260; LYS-3621; LYS-3638 AND LYS-3642, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    55. "A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability."
      Hurov K.E., Cotta-Ramusino C., Elledge S.J.
      Genes Dev. 24:1939-1950(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TTI1.
    56. "Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes."
      Takai H., Xie Y., de Lange T., Pavletich N.P.
      Genes Dev. 24:2019-2030(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TELO2.
    57. "Tti1 and Tel2 are critical factors in mammalian target of rapamycin complex assembly."
      Kaizuka T., Hara T., Oshiro N., Kikkawa U., Yonezawa K., Takehana K., Iemura S., Natsume T., Mizushima N.
      J. Biol. Chem. 285:20109-20116(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TELO2 AND TTI1.
    58. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3205 AND SER-4026, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    59. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    60. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2612 AND SER-3205, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    61. "Systematic analysis of protein pools, isoforms, and modifications affecting turnover and subcellular localization."
      Ahmad Y., Boisvert F.M., Lundberg E., Uhlen M., Lamond A.I.
      Mol. Cell. Proteomics 11:M111.013680.01-M111.013680.15(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
    62. "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.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [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.

    Entry informationi

    Entry nameiPRKDC_HUMAN
    AccessioniPrimary (citable) accession number: P78527
    Secondary accession number(s): P78528
    , Q13327, Q13337, Q14175, Q59H99, Q7Z611, Q96SE6, Q9UME3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 27, 2001
    Last sequence update: October 31, 2003
    Last modified: October 1, 2014
    This is version 160 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 8
      Human chromosome 8: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3