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UniProtKB - P78527 (PRKDC_HUMAN)

Protein

DNA-dependent protein kinase catalytic subunit

Gene

PRKDC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 mechanism. Interacts with CRY1 and CRY2; negatively regulates CRY1 phosphorylation. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Activity regulationi

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

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDNA-binding, Kinase, Serine/threonine-protein kinase, Transferase
Biological processBiological rhythms, DNA damage, DNA recombination, DNA repair, Immunity, Innate immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-1834949 Cytosolic sensors of pathogen-associated DNA
R-HSA-3270619 IRF3-mediated induction of type I IFN
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
SIGNORiP78527

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000253729.7
HGNCiHGNC:9413 PRKDC
MIMi600899 gene
neXtProtiNX_P78527

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 26 with or without neurologic abnormalities (IMD26)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:615966
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0725693062L → R in IMD26; shows increased long palindromic (P)-nucleotide stretches in the immunoglobulin coding joints indicating a defect in hairpin opening and insufficient DCLRE1C activation. 1 PublicationCorresponds to variant dbSNP:rs587777685EnsemblClinVar.1
Natural variantiVAR_0725703574A → V in IMD26; shows impaired function in response to irradiation and a less severe defect in V(D)J end-joining suggesting that the missense mutation retained some functional capacity; consistent with a loss of function mutation. 1 PublicationCorresponds to variant dbSNP:rs587777686EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1510L → P: Loss of interaction with C1D. 1 Publication1
Mutagenesisi1516 – 1517EL → PD: Loss of interaction with C1D. 1 Publication2
Mutagenesisi2609T → A: Leads to radiation sensitivity and impaired DSB joining. Gives rise to reduced phosphorylation; when associated with A-2612. 1 Publication1
Mutagenesisi2612S → A: Reduced phosphorylation; when associated with A-2609. 1
Mutagenesisi2638T → 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 Publication1
Mutagenesisi2647T → 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 Publication1

Keywords - Diseasei

Disease mutation, SCID

Organism-specific databases

DisGeNETi5591
MalaCardsiPRKDC
MIMi615966 phenotype
OpenTargetsiENSG00000253729
Orphaneti317425 Severe combined immunodeficiency due to DNA-PKcs deficiency
PharmGKBiPA33776

Chemistry databases

ChEMBLiCHEMBL3142
DrugBankiDB00201 Caffeine
DB05210 SF1126
GuidetoPHARMACOLOGYi2800

Polymorphism and mutation databases

BioMutaiPRKDC
DMDMi38258929

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002255981 – 4128DNA-dependent protein kinase catalytic subunitAdd BLAST4128

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei117N6-acetyllysineCombined sources1
Modified residuei511PhosphoserineCombined sources1
Modified residuei687PhosphoserineCombined sources1
Modified residuei828N6-acetyllysineCombined sources1
Modified residuei841PhosphoserineCombined sources1
Modified residuei893PhosphoserineCombined sources1
Modified residuei1065PhosphoserineCombined sources1
Modified residuei1209N6-acetyllysineCombined sources1
Modified residuei1970N6-acetyllysineCombined sources1
Modified residuei2056Phosphoserine; by autocatalysis2 Publications1
Modified residuei2259N6-acetyllysineCombined sources1
Modified residuei2535PhosphothreonineCombined sources1
Modified residuei2609Phosphothreonine; by autocatalysis3 Publications1
Modified residuei2612Phosphoserine; by autocatalysisCombined sources1 Publication1
Modified residuei2638Phosphothreonine; by autocatalysisCombined sources1 Publication1
Modified residuei2647Phosphothreonine; by autocatalysisCombined sources1 Publication1
Modified residuei2789PhosphoserineCombined sources1
Modified residuei3205PhosphoserineCombined sources1
Modified residuei3241N6-acetyllysineCombined sources1
Modified residuei3260N6-acetyllysineCombined sources1
Modified residuei3621N6-acetyllysineCombined sources1
Modified residuei3638N6-acetyllysineCombined sources1
Modified residuei3642N6-acetyllysineCombined sources1
Modified residuei3731PhosphoserineCombined sources1
Modified residuei3821PhosphoserineCombined sources1
Modified residuei4026PhosphoserineCombined sources1

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.21 Publications
S-nitrosylated by GAPDH.By similarity
Polyubiquitinated by RNF144A, leading to proteasomal degradation.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei2020 – 2021Cleavage; by caspase-3Curated2

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP78527
MaxQBiP78527
PaxDbiP78527
PeptideAtlasiP78527
PRIDEiP78527
ProteomicsDBi57634
57635 [P78527-2]

2D gel databases

SWISS-2DPAGEiP78527

PTM databases

CarbonylDBiP78527
GlyConnecti1183
iPTMnetiP78527
PhosphoSitePlusiP78527
SwissPalmiP78527

Expressioni

Gene expression databases

BgeeiENSG00000253729 Expressed in 234 organ(s), highest expression level in kidney
ExpressionAtlasiP78527 baseline and differential
GenevisibleiP78527 HS

Organism-specific databases

HPAiCAB005167
HPA035174

Interactioni

Subunit structurei

DNA-PK is a heterotrimer of PRKDC and the Ku p70/YRCC6-p86/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. The DNA-PK heterotrimer associates with the LIG4-XRCC4 complex to form the core of the non-homologous end joining (NHEJ) complex. Additional components of the NHEJ complex include NHEJ1/XLF and PAXX. 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. Interacts with SETX (PubMed:23149945). Interacts with NR4A3; the DNA-dependent protein kinase complex DNA-PK phosphorylates and activates NR4A3 and prevents NR4A3 ubiquitination and degradation (PubMed:25852083). Interacts with BRAT1. Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA.21 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi111577, 277 interactors
ComplexPortaliCPX-3403 DNA-dependent protein kinase complex
CORUMiP78527
DIPiDIP-24186N
ELMiP78527
IntActiP78527, 114 interactors
MINTiP78527
STRINGi9606.ENSP00000313420

Chemistry databases

BindingDBiP78527

Structurei

3D structure databases

ProteinModelPortaliP78527
SMRiP78527
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati288 – 323HEAT 1Add BLAST36
Repeati1004 – 1040HEAT 2Add BLAST37
Repeati1723 – 1756TPR 1Add BLAST34
Domaini2883 – 3539FATPROSITE-ProRule annotationAdd BLAST657
Repeati2920 – 2948TPR 2Add BLAST29
Repeati2949 – 2982TPR 3Add BLAST34
Domaini3747 – 4015PI3K/PI4KPROSITE-ProRule annotationAdd BLAST269
Domaini4096 – 4128FATCPROSITE-ProRule annotationAdd BLAST33

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1503 – 1538Interaction with C1D1 PublicationAdd BLAST36
Regioni1503 – 1538Leucine-zipperAdd BLAST36
Regioni2436 – 3212KIP-bindingAdd BLAST777

Sequence similaritiesi

Belongs to the PI3/PI4-kinase family.Curated

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0891 Eukaryota
COG5032 LUCA
GeneTreeiENSGT00930000150922
HOVERGENiHBG053681
InParanoidiP78527
KOiK06642
OMAiNYSKCTI
OrthoDBiEOG091G0015
PhylomeDBiP78527
TreeFamiTF324494

Family and domain databases

CDDicd05172 PIKKc_DNA-PK, 1 hit
Gene3Di1.10.1070.11, 1 hit
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR037706 DNA-PK_dom
IPR003152 FATC_dom
IPR011009 Kinase-like_dom_sf
IPR012582 NUC194
IPR000403 PI3/4_kinase_cat_dom
IPR036940 PI3/4_kinase_cat_sf
IPR018936 PI3/4_kinase_CS
IPR003151 PIK-rel_kinase_FAT
IPR014009 PIK_FAT
PfamiView protein in Pfam
PF02259 FAT, 1 hit
PF02260 FATC, 1 hit
PF08163 NUC194, 1 hit
PF00454 PI3_PI4_kinase, 1 hit
SMARTiView protein in SMART
SM01343 FATC, 1 hit
SM01344 NUC194, 1 hit
SM00146 PI3Kc, 1 hit
SUPFAMiSSF48371 SSF48371, 3 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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
        10         20         30         40         50
MAGSGAGVRC SLLRLQETLS AADRCGAALA GHQLIRGLGQ ECVLSSSPAV 
        60         70         80         90        100
LALQTSLVFS RDFGLLVFVR KSLNSIEFRE CREEILKFLC IFLEKMGQKI 
       110        120        130        140        150
APYSVEIKNT CTSVYTKDRA AKCKIPALDL LIKLLQTFRS SRLMDEFKIG 
       160        170        180        190        200
ELFSKFYGEL ALKKKIPDTV LEKVYELLGL LGEVHPSEMI NNAENLFRAF 
       210        220        230        240        250
LGELKTQMTS AVREPKLPVL AGCLKGLSSL LCNFTKSMEE DPQTSREIFN 
       260        270        280        290        300
FVLKAIRPQI DLKRYAVPSA GLRLFALHAS QFSTCLLDNY VSLFEVLLKW 
       310        320        330        340        350
CAHTNVELKK AALSALESFL KQVSNMVAKN AEMHKNKLQY FMEQFYGIIR 
       360        370        380        390        400
NVDSNNKELS IAIRGYGLFA GPCKVINAKD VDFMYVELIQ RCKQMFLTQT 
       410        420        430        440        450
DTGDDRVYQM PSFLQSVASV LLYLDTVPEV YTPVLEHLVV MQIDSFPQYS 
       460        470        480        490        500
PKMQLVCCRA IVKVFLALAA KGPVLRNCIS TVVHQGLIRI CSKPVVLPKG 
       510        520        530        540        550
PESESEDHRA SGEVRTGKWK VPTYKDYVDL FRHLLSSDQM MDSILADEAF 
       560        570        580        590        600
FSVNSSSESL NHLLYDEFVK SVLKIVEKLD LTLEIQTVGE QENGDEAPGV 
       610        620        630        640        650
WMIPTSDPAA NLHPAKPKDF SAFINLVEFC REILPEKQAE FFEPWVYSFS 
       660        670        680        690        700
YELILQSTRL PLISGFYKLL SITVRNAKKI KYFEGVSPKS LKHSPEDPEK 
       710        720        730        740        750
YSCFALFVKF GKEVAVKMKQ YKDELLASCL TFLLSLPHNI IELDVRAYVP 
       760        770        780        790        800
ALQMAFKLGL SYTPLAEVGL NALEEWSIYI DRHVMQPYYK DILPCLDGYL 
       810        820        830        840        850
KTSALSDETK NNWEVSALSR AAQKGFNKVV LKHLKKTKNL SSNEAISLEE 
       860        870        880        890        900
IRIRVVQMLG SLGGQINKNL LTVTSSDEMM KSYVAWDREK RLSFAVPFRE 
       910        920        930        940        950
MKPVIFLDVF LPRVTELALT ASDRQTKVAA CELLHSMVMF MLGKATQMPE 
       960        970        980        990       1000
GGQGAPPMYQ LYKRTFPVLL RLACDVDQVT RQLYEPLVMQ LIHWFTNNKK 
      1010       1020       1030       1040       1050
FESQDTVALL EAILDGIVDP VDSTLRDFCG RCIREFLKWS IKQITPQQQE 
      1060       1070       1080       1090       1100
KSPVNTKSLF KRLYSLALHP NAFKRLGASL AFNNIYREFR EEESLVEQFV 
      1110       1120       1130       1140       1150
FEALVIYMES LALAHADEKS LGTIQQCCDA IDHLCRIIEK KHVSLNKAKK 
      1160       1170       1180       1190       1200
RRLPRGFPPS ASLCLLDLVK WLLAHCGRPQ TECRHKSIEL FYKFVPLLPG 
      1210       1220       1230       1240       1250
NRSPNLWLKD VLKEEGVSFL INTFEGGGCG QPSGILAQPT LLYLRGPFSL 
      1260       1270       1280       1290       1300
QATLCWLDLL LAALECYNTF IGERTVGALQ VLGTEAQSSL LKAVAFFLES 
      1310       1320       1330       1340       1350
IAMHDIIAAE KCFGTGAAGN RTSPQEGERY NYSKCTVVVR IMEFTTTLLN 
      1360       1370       1380       1390       1400
TSPEGWKLLK KDLCNTHLMR VLVQTLCEPA SIGFNIGDVQ VMAHLPDVCV 
      1410       1420       1430       1440       1450
NLMKALKMSP YKDILETHLR EKITAQSIEE LCAVNLYGPD AQVDRSRLAA 
      1460       1470       1480       1490       1500
VVSACKQLHR AGLLHNILPS QSTDLHHSVG TELLSLVYKG IAPGDERQCL 
      1510       1520       1530       1540       1550
PSLDLSCKQL ASGLLELAFA FGGLCERLVS LLLNPAVLST ASLGSSQGSV 
      1560       1570       1580       1590       1600
IHFSHGEYFY SLFSETINTE LLKNLDLAVL ELMQSSVDNT KMVSAVLNGM 
      1610       1620       1630       1640       1650
LDQSFRERAN QKHQGLKLAT TILQHWKKCD SWWAKDSPLE TKMAVLALLA 
      1660       1670       1680       1690       1700
KILQIDSSVS FNTSHGSFPE VFTTYISLLA DTKLDLHLKG QAVTLLPFFT 
      1710       1720       1730       1740       1750
SLTGGSLEEL RRVLEQLIVA HFPMQSREFP PGTPRFNNYV DCMKKFLDAL 
      1760       1770       1780       1790       1800
ELSQSPMLLE LMTEVLCREQ QHVMEELFQS SFRRIARRGS CVTQVGLLES 
      1810       1820       1830       1840       1850
VYEMFRKDDP RLSFTRQSFV DRSLLTLLWH CSLDALREFF STIVVDAIDV 
      1860       1870       1880       1890       1900
LKSRFTKLNE STFDTQITKK MGYYKILDVM YSRLPKDDVH AKESKINQVF 
      1910       1920       1930       1940       1950
HGSCITEGNE LTKTLIKLCY DAFTENMAGE NQLLERRRLY HCAAYNCAIS 
      1960       1970       1980       1990       2000
VICCVFNELK FYQGFLFSEK PEKNLLIFEN LIDLKRRYNF PVEVEVPMER 
      2010       2020       2030       2040       2050
KKKYIEIRKE AREAANGDSD GPSYMSSLSY LADSTLSEEM SQFDFSTGVQ 
      2060       2070       2080       2090       2100
SYSYSSQDPR PATGRFRRRE QRDPTVHDDV LELEMDELNR HECMAPLTAL 
      2110       2120       2130       2140       2150
VKHMHRSLGP PQGEEDSVPR DLPSWMKFLH GKLGNPIVPL NIRLFLAKLV 
      2160       2170       2180       2190       2200
INTEEVFRPY AKHWLSPLLQ LAASENNGGE GIHYMVVEIV ATILSWTGLA 
      2210       2220       2230       2240       2250
TPTGVPKDEV LANRLLNFLM KHVFHPKRAV FRHNLEIIKT LVECWKDCLS 
      2260       2270       2280       2290       2300
IPYRLIFEKF SGKDPNSKDN SVGIQLLGIV MANDLPPYDP QCGIQSSEYF 
      2310       2320       2330       2340       2350
QALVNNMSFV RYKEVYAAAA EVLGLILRYV MERKNILEES LCELVAKQLK 
      2360       2370       2380       2390       2400
QHQNTMEDKF IVCLNKVTKS FPPLADRFMN AVFFLLPKFH GVLKTLCLEV 
      2410       2420       2430       2440       2450
VLCRVEGMTE LYFQLKSKDF VQVMRHRDDE RQKVCLDIIY KMMPKLKPVE 
      2460       2470       2480       2490       2500
LRELLNPVVE FVSHPSTTCR EQMYNILMWI HDNYRDPESE TDNDSQEIFK 
      2510       2520       2530       2540       2550
LAKDVLIQGL IDENPGLQLI IRNFWSHETR LPSNTLDRLL ALNSLYSPKI 
      2560       2570       2580       2590       2600
EVHFLSLATN FLLEMTSMSP DYPNPMFEHP LSECEFQEYT IDSDWRFRST 
      2610       2620       2630       2640       2650
VLTPMFVETQ ASQGTLQTRT QEGSLSARWP VAGQIRATQQ QHDFTLTQTA 
      2660       2670       2680       2690       2700
DGRSSFDWLT GSSTDPLVDH TSPSSDSLLF AHKRSERLQR APLKSVGPDF 
      2710       2720       2730       2740       2750
GKKRLGLPGD EVDNKVKGAA GRTDLLRLRR RFMRDQEKLS LMYARKGVAE 
      2760       2770       2780       2790       2800
QKREKEIKSE LKMKQDAQVV LYRSYRHGDL PDIQIKHSSL ITPLQAVAQR 
      2810       2820       2830       2840       2850
DPIIAKQLFS SLFSGILKEM DKFKTLSEKN NITQKLLQDF NRFLNTTFSF 
      2860       2870       2880       2890       2900
FPPFVSCIQD ISCQHAALLS LDPAAVSAGC LASLQQPVGI RLLEEALLRL 
      2910       2920       2930       2940       2950
LPAELPAKRV RGKARLPPDV LRWVELAKLY RSIGEYDVLR GIFTSEIGTK 
      2960       2970       2980       2990       3000
QITQSALLAE ARSDYSEAAK QYDEALNKQD WVDGEPTEAE KDFWELASLD 
      3010       3020       3030       3040       3050
CYNHLAEWKS LEYCSTASID SENPPDLNKI WSEPFYQETY LPYMIRSKLK 
      3060       3070       3080       3090       3100
LLLQGEADQS LLTFIDKAMH GELQKAILEL HYSQELSLLY LLQDDVDRAK 
      3110       3120       3130       3140       3150
YYIQNGIQSF MQNYSSIDVL LHQSRLTKLQ SVQALTEIQE FISFISKQGN 
      3160       3170       3180       3190       3200
LSSQVPLKRL LNTWTNRYPD AKMDPMNIWD DIITNRCFFL SKIEEKLTPL 
      3210       3220       3230       3240       3250
PEDNSMNVDQ DGDPSDRMEV QEQEEDISSL IRSCKFSMKM KMIDSARKQN 
      3260       3270       3280       3290       3300
NFSLAMKLLK ELHKESKTRD DWLVSWVQSY CRLSHCRSRS QGCSEQVLTV 
      3310       3320       3330       3340       3350
LKTVSLLDEN NVSSYLSKNI LAFRDQNILL GTTYRIIANA LSSEPACLAE 
      3360       3370       3380       3390       3400
IEEDKARRIL ELSGSSSEDS EKVIAGLYQR AFQHLSEAVQ AAEEEAQPPS 
      3410       3420       3430       3440       3450
WSCGPAAGVI DAYMTLADFC DQQLRKEEEN ASVIDSAELQ AYPALVVEKM 
      3460       3470       3480       3490       3500
LKALKLNSNE ARLKFPRLLQ IIERYPEETL SLMTKEISSV PCWQFISWIS 
      3510       3520       3530       3540       3550
HMVALLDKDQ AVAVQHSVEE ITDNYPQAIV YPFIISSESY SFKDTSTGHK 
      3560       3570       3580       3590       3600
NKEFVARIKS KLDQGGVIQD FINALDQLSN PELLFKDWSN DVRAELAKTP 
      3610       3620       3630       3640       3650
VNKKNIEKMY ERMYAALGDP KAPGLGAFRR KFIQTFGKEF DKHFGKGGSK 
      3660       3670       3680       3690       3700
LLRMKLSDFN DITNMLLLKM NKDSKPPGNL KECSPWMSDF KVEFLRNELE 
      3710       3720       3730       3740       3750
IPGQYDGRGK PLPEYHVRIA GFDERVTVMA SLRRPKRIII RGHDEREHPF 
      3760       3770       3780       3790       3800
LVKGGEDLRQ DQRVEQLFQV MNGILAQDSA CSQRALQLRT YSVVPMTSRL 
      3810       3820       3830       3840       3850
GLIEWLENTV TLKDLLLNTM SQEEKAAYLS DPRAPPCEYK DWLTKMSGKH 
      3860       3870       3880       3890       3900
DVGAYMLMYK GANRTETVTS FRKRESKVPA DLLKRAFVRM STSPEAFLAL 
      3910       3920       3930       3940       3950
RSHFASSHAL ICISHWILGI GDRHLNNFMV AMETGGVIGI DFGHAFGSAT 
      3960       3970       3980       3990       4000
QFLPVPELMP FRLTRQFINL MLPMKETGLM YSIMVHALRA FRSDPGLLTN 
      4010       4020       4030       4040       4050
TMDVFVKEPS FDWKNFEQKM LKKGGSWIQE INVAEKNWYP RQKICYAKRK 
      4060       4070       4080       4090       4100
LAGANPAVIT CDELLLGHEK APAFRDYVAV ARGSKDHNIR AQEPESGLSE 
      4110       4120 
ETQVKCLMDQ ATDPNILGRT WEGWEPWM
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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YG84H0YG84_HUMAN
DNA-dependent protein kinase cataly...
PRKDC
90Annotation score:
F5GX40F5GX40_HUMAN
DNA-dependent protein kinase cataly...
PRKDC
70Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti405D → Y in AAC50210 (Ref. 2) Curated1
Sequence conflicti1008A → S in AAC50210 (Ref. 2) Curated1
Sequence conflicti3660N → T in AAA79184 (PubMed:7594449).Curated1
Sequence conflicti3817L → W in AAA79184 (PubMed:7594449).Curated1
Sequence conflicti3862A → P in AAA79184 (PubMed:7594449).Curated1
Sequence conflicti4031I → V in AAK40350 (Ref. 9) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0191796A → S2 PublicationsCorresponds to variant dbSNP:rs8177999EnsemblClinVar.1
Natural variantiVAR_041602263K → N in a lung adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs758032015Ensembl.1
Natural variantiVAR_019180333M → I2 PublicationsCorresponds to variant dbSNP:rs8178017EnsemblClinVar.1
Natural variantiVAR_041603420V → I1 PublicationCorresponds to variant dbSNP:rs55925466Ensembl.1
Natural variantiVAR_041604500G → S in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_019181605T → S2 PublicationsCorresponds to variant dbSNP:rs8178033EnsemblClinVar.1
Natural variantiVAR_041605649F → L1 PublicationCorresponds to variant dbSNP:rs55811715Ensembl.1
Natural variantiVAR_019182680I → M1 PublicationCorresponds to variant dbSNP:rs8178040EnsemblClinVar.1
Natural variantiVAR_019183695P → S2 PublicationsCorresponds to variant dbSNP:rs8178046EnsemblClinVar.1
Natural variantiVAR_0191841071N → S1 PublicationCorresponds to variant dbSNP:rs8178070EnsemblClinVar.1
Natural variantiVAR_0416061136R → H in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs781401034Ensembl.1
Natural variantiVAR_0416071190L → V1 PublicationCorresponds to variant dbSNP:rs34598508Ensembl.1
Natural variantiVAR_0416081237A → T1 PublicationCorresponds to variant dbSNP:rs191531119EnsemblClinVar.1
Natural variantiVAR_0416091279L → F1 Publication1
Natural variantiVAR_0191851314G → V1 PublicationCorresponds to variant dbSNP:rs8178090Ensembl.1
Natural variantiVAR_0416101447R → M in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0191861588D → V1 PublicationCorresponds to variant dbSNP:rs8178104Ensembl.1
Natural variantiVAR_0191871603Q → H1 PublicationCorresponds to variant dbSNP:rs8178106EnsemblClinVar.1
Natural variantiVAR_0416111619A → G1 PublicationCorresponds to variant dbSNP:rs56182356Ensembl.1
Natural variantiVAR_0416121680A → V in a metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs55735910Ensembl.1
Natural variantiVAR_0416132023S → P1 PublicationCorresponds to variant dbSNP:rs56042895EnsemblClinVar.1
Natural variantiVAR_0191882095A → V1 PublicationCorresponds to variant dbSNP:rs8178147Ensembl.1
Natural variantiVAR_0416142598R → Q1 PublicationCorresponds to variant dbSNP:rs55923149Ensembl.1
Natural variantiVAR_0191892702K → E1 PublicationCorresponds to variant dbSNP:rs8178178Ensembl.1
Natural variantiVAR_0416152810S → N in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0191902899R → C2 PublicationsCorresponds to variant dbSNP:rs4278157EnsemblClinVar.1
Natural variantiVAR_0416162941G → A in a lung neuroendocrine carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0725693062L → R in IMD26; shows increased long palindromic (P)-nucleotide stretches in the immunoglobulin coding joints indicating a defect in hairpin opening and insufficient DCLRE1C activation. 1 PublicationCorresponds to variant dbSNP:rs587777685EnsemblClinVar.1
Natural variantiVAR_0416173085E → D1 PublicationCorresponds to variant dbSNP:rs56135402Ensembl.1
Natural variantiVAR_0191913149G → D2 PublicationsCorresponds to variant dbSNP:rs8178208EnsemblClinVar.1
Natural variantiVAR_0416183198T → S1 PublicationCorresponds to variant dbSNP:rs55793951Ensembl.1
Natural variantiVAR_0191923201P → S2 PublicationsCorresponds to variant dbSNP:rs8178216EnsemblClinVar.1
Natural variantiVAR_0191933404G → E2 PublicationsCorresponds to variant dbSNP:rs8178225EnsemblClinVar.1
Natural variantiVAR_0191943434I → T2 PublicationsCorresponds to variant dbSNP:rs7830743EnsemblClinVar.1
Natural variantiVAR_0191953459N → S1 PublicationCorresponds to variant dbSNP:rs8178228EnsemblClinVar.1
Natural variantiVAR_0191963562L → M2 PublicationsCorresponds to variant dbSNP:rs8178232EnsemblClinVar.1
Natural variantiVAR_0725703574A → V in IMD26; shows impaired function in response to irradiation and a less severe defect in V(D)J end-joining suggesting that the missense mutation retained some functional capacity; consistent with a loss of function mutation. 1 PublicationCorresponds to variant dbSNP:rs587777686EnsemblClinVar.1
Natural variantiVAR_0416193584L → F1 PublicationCorresponds to variant dbSNP:rs55866966EnsemblClinVar.1
Natural variantiVAR_0505343702P → L. Corresponds to variant dbSNP:rs8178236Ensembl.1
Natural variantiVAR_0416203800L → I1 PublicationCorresponds to variant dbSNP:rs56216442Ensembl.1
Natural variantiVAR_0191973836P → L2 PublicationsCorresponds to variant dbSNP:rs8178245Ensembl.1
Natural variantiVAR_0191983932M → V1 PublicationCorresponds to variant dbSNP:rs8178248Ensembl.1
Natural variantiVAR_0416213936G → S1 PublicationCorresponds to variant dbSNP:rs55670423Ensembl.1
Natural variantiVAR_0416223937V → M1 PublicationCorresponds to variant dbSNP:rs56090750Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0047083799 – 3829Missing in isoform 2. 1 PublicationAdd BLAST31

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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
CCDSiCCDS75734.1 [P78527-2]
CCDS75735.1 [P78527-1]
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 [P78527-1]
ENST00000338368; ENSP00000345182; ENSG00000253729 [P78527-2]
GeneIDi5591
KEGGihsa:5591
UCSCiuc033bkh.1 human [P78527-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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
CCDSiCCDS75734.1 [P78527-2]
CCDS75735.1 [P78527-1]
PIRiA57099
G02083
RefSeqiNP_001075109.1, NM_001081640.1 [P78527-2]
NP_008835.5, NM_006904.6 [P78527-1]
UniGeneiHs.491682

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5LUQX-ray4.30A/B2-2575[»]
A/B2774-4127[»]
5W1Relectron microscopy4.40A1-4128[»]
5Y3Relectron microscopy6.60C10-4128[»]
ProteinModelPortaliP78527
SMRiP78527
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111577, 277 interactors
ComplexPortaliCPX-3403 DNA-dependent protein kinase complex
CORUMiP78527
DIPiDIP-24186N
ELMiP78527
IntActiP78527, 114 interactors
MINTiP78527
STRINGi9606.ENSP00000313420

Chemistry databases

BindingDBiP78527
ChEMBLiCHEMBL3142
DrugBankiDB00201 Caffeine
DB05210 SF1126
GuidetoPHARMACOLOGYi2800

PTM databases

CarbonylDBiP78527
GlyConnecti1183
iPTMnetiP78527
PhosphoSitePlusiP78527
SwissPalmiP78527

Polymorphism and mutation databases

BioMutaiPRKDC
DMDMi38258929

2D gel databases

SWISS-2DPAGEiP78527

Proteomic databases

EPDiP78527
MaxQBiP78527
PaxDbiP78527
PeptideAtlasiP78527
PRIDEiP78527
ProteomicsDBi57634
57635 [P78527-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000314191; ENSP00000313420; ENSG00000253729 [P78527-1]
ENST00000338368; ENSP00000345182; ENSG00000253729 [P78527-2]
GeneIDi5591
KEGGihsa:5591
UCSCiuc033bkh.1 human [P78527-1]

Organism-specific databases

CTDi5591
DisGeNETi5591
EuPathDBiHostDB:ENSG00000253729.7
GeneCardsiPRKDC
HGNCiHGNC:9413 PRKDC
HPAiCAB005167
HPA035174
MalaCardsiPRKDC
MIMi600899 gene
615966 phenotype
neXtProtiNX_P78527
OpenTargetsiENSG00000253729
Orphaneti317425 Severe combined immunodeficiency due to DNA-PKcs deficiency
PharmGKBiPA33776
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0891 Eukaryota
COG5032 LUCA
GeneTreeiENSGT00930000150922
HOVERGENiHBG053681
InParanoidiP78527
KOiK06642
OMAiNYSKCTI
OrthoDBiEOG091G0015
PhylomeDBiP78527
TreeFamiTF324494

Enzyme and pathway databases

ReactomeiR-HSA-1834949 Cytosolic sensors of pathogen-associated DNA
R-HSA-3270619 IRF3-mediated induction of type I IFN
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
SIGNORiP78527

Miscellaneous databases

ChiTaRSiPRKDC human
GeneWikiiDNA-PKcs
GenomeRNAii5591
PROiPR:P78527
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000253729 Expressed in 234 organ(s), highest expression level in kidney
ExpressionAtlasiP78527 baseline and differential
GenevisibleiP78527 HS

Family and domain databases

CDDicd05172 PIKKc_DNA-PK, 1 hit
Gene3Di1.10.1070.11, 1 hit
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR037706 DNA-PK_dom
IPR003152 FATC_dom
IPR011009 Kinase-like_dom_sf
IPR012582 NUC194
IPR000403 PI3/4_kinase_cat_dom
IPR036940 PI3/4_kinase_cat_sf
IPR018936 PI3/4_kinase_CS
IPR003151 PIK-rel_kinase_FAT
IPR014009 PIK_FAT
PfamiView protein in Pfam
PF02259 FAT, 1 hit
PF02260 FATC, 1 hit
PF08163 NUC194, 1 hit
PF00454 PI3_PI4_kinase, 1 hit
SMARTiView protein in SMART
SM01343 FATC, 1 hit
SM01344 NUC194, 1 hit
SM00146 PI3Kc, 1 hit
SUPFAMiSSF48371 SSF48371, 3 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
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
ProtoNetiSearch...

Entry informationi

Entry nameiPRKDC_HUMAN
AccessioniPrimary (citable) accession number: P78527
Secondary accession number(s): P78528
, Q13327, Q13337, Q14175, Q59H99, Q7Z611, Q96SE6, Q9UME3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: October 31, 2003
Last modified: November 7, 2018
This is version 206 of the entry and version 3 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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