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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

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti3062 – 30621L → 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 Publication
Corresponds to variant rs587777685 [ dbSNP | Ensembl ].
VAR_072569
Natural varianti3574 – 35741A → 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 Publication
Corresponds to variant rs587777686 [ dbSNP | Ensembl ].
VAR_072570

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. 1 Publication
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

Keywords - Diseasei

Disease mutation, SCID

Organism-specific databases

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

Chemistry

ChEMBLiCHEMBL3142.
DrugBankiDB00201. Caffeine.
GuidetoPHARMACOLOGYi2800.

Polymorphism and mutation databases

BioMutaiPRKDC.
DMDMi38258929.

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-acetyllysineCombined sources
Modified residuei511 – 5111PhosphoserineCombined sources
Modified residuei687 – 6871PhosphoserineCombined sources
Modified residuei828 – 8281N6-acetyllysineCombined sources
Modified residuei841 – 8411PhosphoserineCombined sources
Modified residuei893 – 8931PhosphoserineCombined sources
Modified residuei1065 – 10651PhosphoserineCombined sources
Modified residuei1209 – 12091N6-acetyllysineCombined sources
Modified residuei1970 – 19701N6-acetyllysineCombined sources
Modified residuei2056 – 20561Phosphoserine; by autocatalysis2 Publications
Modified residuei2259 – 22591N6-acetyllysineCombined sources
Modified residuei2535 – 25351PhosphothreonineCombined sources
Modified residuei2609 – 26091Phosphothreonine; by autocatalysis3 Publications
Modified residuei2612 – 26121Phosphoserine; by autocatalysisCombined sources1 Publication
Modified residuei2638 – 26381Phosphothreonine; by autocatalysisCombined sources1 Publication
Modified residuei2647 – 26471Phosphothreonine; by autocatalysisCombined sources1 Publication
Modified residuei2789 – 27891PhosphoserineCombined sources
Modified residuei3205 – 32051PhosphoserineCombined sources
Modified residuei3241 – 32411N6-acetyllysineCombined sources
Modified residuei3260 – 32601N6-acetyllysineCombined sources
Modified residuei3621 – 36211N6-acetyllysineCombined sources
Modified residuei3638 – 36381N6-acetyllysineCombined sources
Modified residuei3642 – 36421N6-acetyllysineCombined sources
Modified residuei3731 – 37311PhosphoserineCombined sources
Modified residuei3821 – 38211PhosphoserineCombined sources
Modified residuei4026 – 40261PhosphoserineCombined sources

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)LengthDescriptionGraphical viewFeature identifierActions
Sitei2020 – 20212Cleavage; by caspase-3Curated

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP78527.
MaxQBiP78527.
PaxDbiP78527.
PeptideAtlasiP78527.
PRIDEiP78527.

2D gel databases

SWISS-2DPAGEP78527.

PTM databases

iPTMnetiP78527.
PhosphoSiteiP78527.
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. 249 interactions.
DIPiDIP-24186N.
IntActiP78527. 97 interactions.
MINTiMINT-5006046.
STRINGi9606.ENSP00000313420.

Chemistry

BindingDBiP78527.

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

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.

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        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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti405 – 4051D → Y in AAC50210 (Ref. 2) Curated
Sequence conflicti1008 – 10081A → S in AAC50210 (Ref. 2) Curated
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 (Ref. 9) Curated

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
Corresponds to variant rs758032015 [ dbSNP | Ensembl ].
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
Corresponds to variant rs781401034 [ dbSNP | Ensembl ].
VAR_041606
Natural varianti1190 – 11901L → V.1 Publication
Corresponds to variant rs34598508 [ dbSNP | Ensembl ].
VAR_041607
Natural varianti1237 – 12371A → T.1 Publication
Corresponds to variant rs191531119 [ dbSNP | Ensembl ].
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 varianti3062 – 30621L → 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 Publication
Corresponds to variant rs587777685 [ dbSNP | Ensembl ].
VAR_072569
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 varianti3574 – 35741A → 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 Publication
Corresponds to variant rs587777686 [ dbSNP | Ensembl ].
VAR_072570
Natural varianti3584 – 35841L → F.1 Publication
Corresponds to variant rs55866966 [ dbSNP | Ensembl ].
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
Corresponds to variant rs8178248 [ dbSNP | Ensembl ].
VAR_019198
Natural varianti3936 – 39361G → S.1 Publication
Corresponds to variant rs55670423 [ dbSNP | Ensembl ].
VAR_041621
Natural varianti3937 – 39371V → M.1 Publication
Corresponds to variant rs56090750 [ dbSNP | Ensembl ].
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:
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.
SMRiP78527. Positions 3724-3998.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111577. 249 interactions.
DIPiDIP-24186N.
IntActiP78527. 97 interactions.
MINTiMINT-5006046.
STRINGi9606.ENSP00000313420.

Chemistry

BindingDBiP78527.
ChEMBLiCHEMBL3142.
DrugBankiDB00201. Caffeine.
GuidetoPHARMACOLOGYi2800.

PTM databases

iPTMnetiP78527.
PhosphoSiteiP78527.
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.
GeneCardsiPRKDC.
HGNCiHGNC:9413. PRKDC.
HPAiCAB005167.
HPA035174.
MalaCardsiPRKDC.
MIMi600899. gene.
615966. phenotype.
neXtProtiNX_P78527.
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

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: September 7, 2016
This is version 181 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.