Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJVS4EG)

DOT Name DNA-dependent protein kinase catalytic subunit (PRKDC)
Synonyms DNA-PK catalytic subunit; DNA-PKcs; EC 2.7.11.1; DNPK1; p460
Gene Name PRKDC
Related Disease
Severe combined immunodeficiency due to DNA-PKcs deficiency ( )
UniProt ID
PRKDC_HUMAN
PDB ID
5LUQ ; 5W1R ; 5Y3R ; 6ZFP ; 6ZH2 ; 6ZH4 ; 6ZH6 ; 6ZH8 ; 6ZHA ; 6ZHE ; 7K0Y ; 7K10 ; 7K11 ; 7K19 ; 7K1B ; 7K1J ; 7K1K ; 7K1N ; 7LT3 ; 7NFC ; 7NFE ; 7OTM ; 7OTP ; 7OTV ; 7OTW ; 7OTY ; 7SGL ; 7SU3 ; 7SUD ; 7TYR ; 7Z87 ; 7Z88 ; 8BH3 ; 8BHV ; 8BHY ; 8BOT ; 8EZ9 ; 8EZA ; 8EZB
EC Number
2.7.11.1
Pfam ID
PF20500 ; PF20502 ; PF08163 ; PF19704 ; PF02259 ; PF02260 ; PF00454
Sequence
MAGSGAGVRCSLLRLQETLSAADRCGAALAGHQLIRGLGQECVLSSSPAVLALQTSLVFS
RDFGLLVFVRKSLNSIEFRECREEILKFLCIFLEKMGQKIAPYSVEIKNTCTSVYTKDRA
AKCKIPALDLLIKLLQTFRSSRLMDEFKIGELFSKFYGELALKKKIPDTVLEKVYELLGL
LGEVHPSEMINNAENLFRAFLGELKTQMTSAVREPKLPVLAGCLKGLSSLLCNFTKSMEE
DPQTSREIFNFVLKAIRPQIDLKRYAVPSAGLRLFALHASQFSTCLLDNYVSLFEVLLKW
CAHTNVELKKAALSALESFLKQVSNMVAKNAEMHKNKLQYFMEQFYGIIRNVDSNNKELS
IAIRGYGLFAGPCKVINAKDVDFMYVELIQRCKQMFLTQTDTGDDRVYQMPSFLQSVASV
LLYLDTVPEVYTPVLEHLVVMQIDSFPQYSPKMQLVCCRAIVKVFLALAAKGPVLRNCIS
TVVHQGLIRICSKPVVLPKGPESESEDHRASGEVRTGKWKVPTYKDYVDLFRHLLSSDQM
MDSILADEAFFSVNSSSESLNHLLYDEFVKSVLKIVEKLDLTLEIQTVGEQENGDEAPGV
WMIPTSDPAANLHPAKPKDFSAFINLVEFCREILPEKQAEFFEPWVYSFSYELILQSTRL
PLISGFYKLLSITVRNAKKIKYFEGVSPKSLKHSPEDPEKYSCFALFVKFGKEVAVKMKQ
YKDELLASCLTFLLSLPHNIIELDVRAYVPALQMAFKLGLSYTPLAEVGLNALEEWSIYI
DRHVMQPYYKDILPCLDGYLKTSALSDETKNNWEVSALSRAAQKGFNKVVLKHLKKTKNL
SSNEAISLEEIRIRVVQMLGSLGGQINKNLLTVTSSDEMMKSYVAWDREKRLSFAVPFRE
MKPVIFLDVFLPRVTELALTASDRQTKVAACELLHSMVMFMLGKATQMPEGGQGAPPMYQ
LYKRTFPVLLRLACDVDQVTRQLYEPLVMQLIHWFTNNKKFESQDTVALLEAILDGIVDP
VDSTLRDFCGRCIREFLKWSIKQITPQQQEKSPVNTKSLFKRLYSLALHPNAFKRLGASL
AFNNIYREFREEESLVEQFVFEALVIYMESLALAHADEKSLGTIQQCCDAIDHLCRIIEK
KHVSLNKAKKRRLPRGFPPSASLCLLDLVKWLLAHCGRPQTECRHKSIELFYKFVPLLPG
NRSPNLWLKDVLKEEGVSFLINTFEGGGCGQPSGILAQPTLLYLRGPFSLQATLCWLDLL
LAALECYNTFIGERTVGALQVLGTEAQSSLLKAVAFFLESIAMHDIIAAEKCFGTGAAGN
RTSPQEGERYNYSKCTVVVRIMEFTTTLLNTSPEGWKLLKKDLCNTHLMRVLVQTLCEPA
SIGFNIGDVQVMAHLPDVCVNLMKALKMSPYKDILETHLREKITAQSIEELCAVNLYGPD
AQVDRSRLAAVVSACKQLHRAGLLHNILPSQSTDLHHSVGTELLSLVYKGIAPGDERQCL
PSLDLSCKQLASGLLELAFAFGGLCERLVSLLLNPAVLSTASLGSSQGSVIHFSHGEYFY
SLFSETINTELLKNLDLAVLELMQSSVDNTKMVSAVLNGMLDQSFRERANQKHQGLKLAT
TILQHWKKCDSWWAKDSPLETKMAVLALLAKILQIDSSVSFNTSHGSFPEVFTTYISLLA
DTKLDLHLKGQAVTLLPFFTSLTGGSLEELRRVLEQLIVAHFPMQSREFPPGTPRFNNYV
DCMKKFLDALELSQSPMLLELMTEVLCREQQHVMEELFQSSFRRIARRGSCVTQVGLLES
VYEMFRKDDPRLSFTRQSFVDRSLLTLLWHCSLDALREFFSTIVVDAIDVLKSRFTKLNE
STFDTQITKKMGYYKILDVMYSRLPKDDVHAKESKINQVFHGSCITEGNELTKTLIKLCY
DAFTENMAGENQLLERRRLYHCAAYNCAISVICCVFNELKFYQGFLFSEKPEKNLLIFEN
LIDLKRRYNFPVEVEVPMERKKKYIEIRKEAREAANGDSDGPSYMSSLSYLADSTLSEEM
SQFDFSTGVQSYSYSSQDPRPATGRFRRREQRDPTVHDDVLELEMDELNRHECMAPLTAL
VKHMHRSLGPPQGEEDSVPRDLPSWMKFLHGKLGNPIVPLNIRLFLAKLVINTEEVFRPY
AKHWLSPLLQLAASENNGGEGIHYMVVEIVATILSWTGLATPTGVPKDEVLANRLLNFLM
KHVFHPKRAVFRHNLEIIKTLVECWKDCLSIPYRLIFEKFSGKDPNSKDNSVGIQLLGIV
MANDLPPYDPQCGIQSSEYFQALVNNMSFVRYKEVYAAAAEVLGLILRYVMERKNILEES
LCELVAKQLKQHQNTMEDKFIVCLNKVTKSFPPLADRFMNAVFFLLPKFHGVLKTLCLEV
VLCRVEGMTELYFQLKSKDFVQVMRHRDDERQKVCLDIIYKMMPKLKPVELRELLNPVVE
FVSHPSTTCREQMYNILMWIHDNYRDPESETDNDSQEIFKLAKDVLIQGLIDENPGLQLI
IRNFWSHETRLPSNTLDRLLALNSLYSPKIEVHFLSLATNFLLEMTSMSPDYPNPMFEHP
LSECEFQEYTIDSDWRFRSTVLTPMFVETQASQGTLQTRTQEGSLSARWPVAGQIRATQQ
QHDFTLTQTADGRSSFDWLTGSSTDPLVDHTSPSSDSLLFAHKRSERLQRAPLKSVGPDF
GKKRLGLPGDEVDNKVKGAAGRTDLLRLRRRFMRDQEKLSLMYARKGVAEQKREKEIKSE
LKMKQDAQVVLYRSYRHGDLPDIQIKHSSLITPLQAVAQRDPIIAKQLFSSLFSGILKEM
DKFKTLSEKNNITQKLLQDFNRFLNTTFSFFPPFVSCIQDISCQHAALLSLDPAAVSAGC
LASLQQPVGIRLLEEALLRLLPAELPAKRVRGKARLPPDVLRWVELAKLYRSIGEYDVLR
GIFTSEIGTKQITQSALLAEARSDYSEAAKQYDEALNKQDWVDGEPTEAEKDFWELASLD
CYNHLAEWKSLEYCSTASIDSENPPDLNKIWSEPFYQETYLPYMIRSKLKLLLQGEADQS
LLTFIDKAMHGELQKAILELHYSQELSLLYLLQDDVDRAKYYIQNGIQSFMQNYSSIDVL
LHQSRLTKLQSVQALTEIQEFISFISKQGNLSSQVPLKRLLNTWTNRYPDAKMDPMNIWD
DIITNRCFFLSKIEEKLTPLPEDNSMNVDQDGDPSDRMEVQEQEEDISSLIRSCKFSMKM
KMIDSARKQNNFSLAMKLLKELHKESKTRDDWLVSWVQSYCRLSHCRSRSQGCSEQVLTV
LKTVSLLDENNVSSYLSKNILAFRDQNILLGTTYRIIANALSSEPACLAEIEEDKARRIL
ELSGSSSEDSEKVIAGLYQRAFQHLSEAVQAAEEEAQPPSWSCGPAAGVIDAYMTLADFC
DQQLRKEEENASVIDSAELQAYPALVVEKMLKALKLNSNEARLKFPRLLQIIERYPEETL
SLMTKEISSVPCWQFISWISHMVALLDKDQAVAVQHSVEEITDNYPQAIVYPFIISSESY
SFKDTSTGHKNKEFVARIKSKLDQGGVIQDFINALDQLSNPELLFKDWSNDVRAELAKTP
VNKKNIEKMYERMYAALGDPKAPGLGAFRRKFIQTFGKEFDKHFGKGGSKLLRMKLSDFN
DITNMLLLKMNKDSKPPGNLKECSPWMSDFKVEFLRNELEIPGQYDGRGKPLPEYHVRIA
GFDERVTVMASLRRPKRIIIRGHDEREHPFLVKGGEDLRQDQRVEQLFQVMNGILAQDSA
CSQRALQLRTYSVVPMTSRLGLIEWLENTVTLKDLLLNTMSQEEKAAYLSDPRAPPCEYK
DWLTKMSGKHDVGAYMLMYKGANRTETVTSFRKRESKVPADLLKRAFVRMSTSPEAFLAL
RSHFASSHALICISHWILGIGDRHLNNFMVAMETGGVIGIDFGHAFGSATQFLPVPELMP
FRLTRQFINLMLPMKETGLMYSIMVHALRAFRSDPGLLTNTMDVFVKEPSFDWKNFEQKM
LKKGGSWIQEINVAEKNWYPRQKICYAKRKLAGANPAVITCDELLLGHEKAPAFRDYVAV
ARGSKDHNIRAQEPESGLSEETQVKCLMDQATDPNILGRTWEGWEPWM
Function
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). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ. Act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage. The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step. 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. As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome. Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism. Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, 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. 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. Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation. Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1.
KEGG Pathway
Non-homologous end-joining (hsa03450 )
Cell cycle (hsa04110 )
Reactome Pathway
IRF3-mediated induction of type I IFN (R-HSA-3270619 )
Nonhomologous End-Joining (NHEJ) (R-HSA-5693571 )
E3 ubiquitin ligases ubiquitinate target proteins (R-HSA-8866654 )
Cytosolic sensors of pathogen-associated DNA (R-HSA-1834949 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Severe combined immunodeficiency due to DNA-PKcs deficiency DISGPSAD Definitive Autosomal recessive [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Josamycin DMKJ8LB Approved DNA-dependent protein kinase catalytic subunit (PRKDC) affects the response to substance of Josamycin. [41]
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36 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [2]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [4]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [6]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [8]
Arsenic DMTL2Y1 Approved Arsenic decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [9]
Quercetin DM3NC4M Approved Quercetin decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [10]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [11]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [12]
Marinol DM70IK5 Approved Marinol increases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [14]
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [15]
Folic acid DMEMBJC Approved Folic acid affects the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [16]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [17]
Bortezomib DMNO38U Approved Bortezomib decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [18]
Hydroquinone DM6AVR4 Approved Hydroquinone increases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [19]
Acocantherin DM7JT24 Approved Acocantherin decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [22]
Acetic Acid, Glacial DM4SJ5Y Approved Acetic Acid, Glacial increases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [23]
Motexafin gadolinium DMEJKRF Approved Motexafin gadolinium increases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [23]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [24]
Tamibarotene DM3G74J Phase 3 Tamibarotene decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [3]
Curcumin DMQPH29 Phase 3 Curcumin decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [25]
Phenol DM1QSM3 Phase 2/3 Phenol increases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [26]
Afimoxifene DMFORDT Phase 2 Afimoxifene decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [15]
Arecoline DMFJZK3 Phase 1 Arecoline decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [29]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [7]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [31]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [32]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [33]
Glyphosate DM0AFY7 Investigative Glyphosate decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [34]
GALLICACID DM6Y3A0 Investigative GALLICACID decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [35]
Nickel chloride DMI12Y8 Investigative Nickel chloride increases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [36]
4-hydroxy-2-nonenal DM2LJFZ Investigative 4-hydroxy-2-nonenal decreases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [37]
CH-223191 DMMJZYC Investigative CH-223191 increases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [38]
USNIC ACID DMGOURX Investigative USNIC ACID increases the expression of DNA-dependent protein kinase catalytic subunit (PRKDC). [39]
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⏷ Show the Full List of 36 Drug(s)
8 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Decitabine DMQL8XJ Approved Decitabine affects the methylation of DNA-dependent protein kinase catalytic subunit (PRKDC). [13]
Etoposide DMNH3PG Approved Etoposide increases the phosphorylation of DNA-dependent protein kinase catalytic subunit (PRKDC). [20]
Irinotecan DMP6SC2 Approved Irinotecan increases the phosphorylation of DNA-dependent protein kinase catalytic subunit (PRKDC). [20]
Capsaicin DMGMF6V Approved Capsaicin increases the phosphorylation of DNA-dependent protein kinase catalytic subunit (PRKDC). [21]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of DNA-dependent protein kinase catalytic subunit (PRKDC). [28]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of DNA-dependent protein kinase catalytic subunit (PRKDC). [30]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of DNA-dependent protein kinase catalytic subunit (PRKDC). [30]
KU-55933 DMDT42X Investigative KU-55933 decreases the phosphorylation of DNA-dependent protein kinase catalytic subunit (PRKDC). [40]
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⏷ Show the Full List of 8 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
DNCB DMDTVYC Phase 2 DNCB affects the binding of DNA-dependent protein kinase catalytic subunit (PRKDC). [27]
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References

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