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Protein

DNA-dependent protein kinase catalytic subunit

Gene

PRKDC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 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

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • DNA-dependent protein kinase activity Source: MGI
  • double-stranded DNA binding Source: Ensembl
  • poly(A) RNA binding Source: UniProtKB
  • protein kinase activity Source: CACAO
  • protein serine/threonine kinase activity Source: BHF-UCL
  • transcription factor binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

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

BioCyciZFISH:HS04461-MONOMER.
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).
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:9413. PRKDC.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • DNA-dependent protein kinase-DNA ligase 4 complex Source: MGI
  • extracellular matrix Source: BHF-UCL
  • membrane Source: UniProtKB
  • nonhomologous end joining complex Source: UniProtKB
  • nuclear chromosome, telomeric region Source: BHF-UCL
  • nucleolus Source: UniProtKB-SubCell
  • nucleoplasm Source: HPA
  • transcription factor complex Source: BHF-UCL
Complete GO annotation...

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 rs587777685dbSNPEnsembl.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 rs587777686dbSNPEnsembl.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.
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.

2D gel databases

SWISS-2DPAGEP78527.

PTM databases

iPTMnetiP78527.
PhosphoSitePlusiP78527.
SwissPalmiP78527.

Expressioni

Gene expression databases

BgeeiENSG00000253729.
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 C9ORF142/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 ubiquitinylation and degradation (PubMed:25852083). Interacts with BRAT1.20 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AIREO439182EBI-352053,EBI-1753081
CASP2P425754EBI-352053,EBI-520342
DCLRE1CQ96SD14EBI-352053,EBI-11694104
ETS1P149212EBI-352053,EBI-913209
ETV1P505492EBI-352053,EBI-3905068
HOXB7P096292EBI-352053,EBI-1248457
IGFBP3P179362EBI-352053,EBI-715709
MAPKAP1Q9BPZ72EBI-352053,EBI-749938
NR1H4Q96RI1-24EBI-352053,EBI-9640524
PIDD1Q9HB756EBI-352053,EBI-520427
RARAP102763EBI-352053,EBI-413374
SPI1P179472EBI-352053,EBI-2293548
XRCC5P130107EBI-352053,EBI-357997
XRCC6P129566EBI-352053,EBI-353208
YY1P254902EBI-352053,EBI-765538

GO - Molecular functioni

  • transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi111577. 250 interactors.
DIPiDIP-24186N.
IntActiP78527. 98 interactors.
MINTiMINT-5006046.
STRINGi9606.ENSP00000313420.

Chemistry databases

BindingDBiP78527.

Structurei

3D structure databases

ProteinModelPortaliP78527.
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
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

eggNOGiKOG0891. Eukaryota.
COG5032. LUCA.
GeneTreeiENSGT00830000128321.
HOVERGENiHBG053681.
InParanoidiP78527.
KOiK06642.
OMAiLVEQFVF.
OrthoDBiEOG091G0015.
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_dom.
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]
SMARTiSM01343. FATC. 1 hit.
SM01344. NUC194. 1 hit.
SM00146. 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. AlignAdd to basket

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

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 → S.2 PublicationsCorresponds to variant rs8177999dbSNPEnsembl.1
Natural variantiVAR_041602263K → N in a lung adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant rs758032015dbSNPEnsembl.1
Natural variantiVAR_019180333M → I.2 PublicationsCorresponds to variant rs8178017dbSNPEnsembl.1
Natural variantiVAR_041603420V → I.1 PublicationCorresponds to variant rs55925466dbSNPEnsembl.1
Natural variantiVAR_041604500G → S in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_019181605T → S.2 PublicationsCorresponds to variant rs8178033dbSNPEnsembl.1
Natural variantiVAR_041605649F → L.1 PublicationCorresponds to variant rs55811715dbSNPEnsembl.1
Natural variantiVAR_019182680I → M.1 PublicationCorresponds to variant rs8178040dbSNPEnsembl.1
Natural variantiVAR_019183695P → S.2 PublicationsCorresponds to variant rs8178046dbSNPEnsembl.1
Natural variantiVAR_0191841071N → S.1 PublicationCorresponds to variant rs8178070dbSNPEnsembl.1
Natural variantiVAR_0416061136R → H in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant rs781401034dbSNPEnsembl.1
Natural variantiVAR_0416071190L → V.1 PublicationCorresponds to variant rs34598508dbSNPEnsembl.1
Natural variantiVAR_0416081237A → T.1 PublicationCorresponds to variant rs191531119dbSNPEnsembl.1
Natural variantiVAR_0416091279L → F.1 Publication1
Natural variantiVAR_0191851314G → V.1 PublicationCorresponds to variant rs8178090dbSNPEnsembl.1
Natural variantiVAR_0416101447R → M in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0191861588D → V.1 PublicationCorresponds to variant rs8178104dbSNPEnsembl.1
Natural variantiVAR_0191871603Q → H.1 PublicationCorresponds to variant rs8178106dbSNPEnsembl.1
Natural variantiVAR_0416111619A → G.1 PublicationCorresponds to variant rs56182356dbSNPEnsembl.1
Natural variantiVAR_0416121680A → V in a metastatic melanoma sample; somatic mutation. 1 PublicationCorresponds to variant rs55735910dbSNPEnsembl.1
Natural variantiVAR_0416132023S → P.1 PublicationCorresponds to variant rs56042895dbSNPEnsembl.1
Natural variantiVAR_0191882095A → V.1 PublicationCorresponds to variant rs8178147dbSNPEnsembl.1
Natural variantiVAR_0416142598R → Q.1 PublicationCorresponds to variant rs55923149dbSNPEnsembl.1
Natural variantiVAR_0191892702K → E.1 PublicationCorresponds to variant rs8178178dbSNPEnsembl.1
Natural variantiVAR_0416152810S → N in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0191902899R → C.2 PublicationsCorresponds to variant rs4278157dbSNPEnsembl.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 rs587777685dbSNPEnsembl.1
Natural variantiVAR_0416173085E → D.1 PublicationCorresponds to variant rs56135402dbSNPEnsembl.1
Natural variantiVAR_0191913149G → D.2 PublicationsCorresponds to variant rs8178208dbSNPEnsembl.1
Natural variantiVAR_0416183198T → S.1 PublicationCorresponds to variant rs55793951dbSNPEnsembl.1
Natural variantiVAR_0191923201P → S.2 PublicationsCorresponds to variant rs8178216dbSNPEnsembl.1
Natural variantiVAR_0191933404G → E.2 PublicationsCorresponds to variant rs8178225dbSNPEnsembl.1
Natural variantiVAR_0191943434I → T.2 PublicationsCorresponds to variant rs7830743dbSNPEnsembl.1
Natural variantiVAR_0191953459N → S.1 PublicationCorresponds to variant rs8178228dbSNPEnsembl.1
Natural variantiVAR_0191963562L → M.2 PublicationsCorresponds to variant rs8178232dbSNPEnsembl.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 rs587777686dbSNPEnsembl.1
Natural variantiVAR_0416193584L → F.1 PublicationCorresponds to variant rs55866966dbSNPEnsembl.1
Natural variantiVAR_0505343702P → L.Corresponds to variant rs8178236dbSNPEnsembl.1
Natural variantiVAR_0416203800L → I.1 PublicationCorresponds to variant rs56216442dbSNPEnsembl.1
Natural variantiVAR_0191973836P → L.2 PublicationsCorresponds to variant rs8178245dbSNPEnsembl.1
Natural variantiVAR_0191983932M → V.1 PublicationCorresponds to variant rs8178248dbSNPEnsembl.1
Natural variantiVAR_0416213936G → S.1 PublicationCorresponds to variant rs55670423dbSNPEnsembl.1
Natural variantiVAR_0416223937V → M.1 PublicationCorresponds to variant rs56090750dbSNPEnsembl.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

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

ProteinModelPortaliP78527.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111577. 250 interactors.
DIPiDIP-24186N.
IntActiP78527. 98 interactors.
MINTiMINT-5006046.
STRINGi9606.ENSP00000313420.

Chemistry databases

BindingDBiP78527.
ChEMBLiCHEMBL3142.
DrugBankiDB00201. Caffeine.
GuidetoPHARMACOLOGYi2800.

PTM databases

iPTMnetiP78527.
PhosphoSitePlusiP78527.
SwissPalmiP78527.

Polymorphism and mutation databases

BioMutaiPRKDC.
DMDMi38258929.

2D gel databases

SWISS-2DPAGEP78527.

Proteomic databases

EPDiP78527.
MaxQBiP78527.
PaxDbiP78527.
PeptideAtlasiP78527.
PRIDEiP78527.

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.
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.
GeneTreeiENSGT00830000128321.
HOVERGENiHBG053681.
InParanoidiP78527.
KOiK06642.
OMAiLVEQFVF.
OrthoDBiEOG091G0015.
PhylomeDBiP78527.
TreeFamiTF324494.

Enzyme and pathway databases

BioCyciZFISH:HS04461-MONOMER.
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).
SIGNORiP78527.

Miscellaneous databases

ChiTaRSiPRKDC. human.
GeneWikiiDNA-PKcs.
GenomeRNAii5591.
PROiP78527.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000253729.
ExpressionAtlasiP78527. baseline and differential.
GenevisibleiP78527. HS.

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_dom.
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]
SMARTiSM01343. FATC. 1 hit.
SM01344. NUC194. 1 hit.
SM00146. 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]
ProtoNetiSearch...

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: November 30, 2016
This is version 184 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.