Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT310QSG)

DOT Name Poly polymerase 1 (PARP1)
Synonyms
PARP-1; EC 2.4.2.30; ADP-ribosyltransferase diphtheria toxin-like 1; ARTD1; DNA ADP-ribosyltransferase PARP1; EC 2.4.2.-; NAD(+) ADP-ribosyltransferase 1; ADPRT 1; Poly synthase 1; Protein poly-ADP-ribosyltransferase PARP1; EC 2.4.2.-) polymerase 1, processed C-terminus (Poly polymerase 1, 89-kDa form); Poly polymerase 1, processed N-terminus (NT-PARP-1; Poly polymerase 1, 24-kDa form; Poly polymerase 1, 28-kDa form)]
Gene Name PARP1
UniProt ID
PARP1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1UK0 ; 1UK1 ; 1WOK ; 2COK ; 2CR9 ; 2CS2 ; 2DMJ ; 2JVN ; 2L30 ; 2L31 ; 2N8A ; 2RCW ; 2RD6 ; 2RIQ ; 3GJW ; 3GN7 ; 3L3L ; 3L3M ; 3OD8 ; 3ODA ; 3ODC ; 3ODE ; 4AV1 ; 4DQY ; 4GV7 ; 4HHY ; 4HHZ ; 4L6S ; 4OPX ; 4OQA ; 4OQB ; 4PJT ; 4R5W ; 4R6E ; 4RV6 ; 4UND ; 4UXB ; 4XHU ; 4ZZZ ; 5A00 ; 5DS3 ; 5HA9 ; 5KPN ; 5KPO ; 5KPP ; 5KPQ ; 5WRQ ; 5WRY ; 5WRZ ; 5WS0 ; 5WS1 ; 5WTC ; 5XSR ; 5XST ; 5XSU ; 6BHV ; 6GHK ; 6M3I ; 6NRF ; 6NRG ; 6NRH ; 6NRI ; 6NRJ ; 6NTU ; 6VKK ; 6VKO ; 6VKQ ; 6XVW ; 7AAA ; 7AAB ; 7AAC ; 7AAD ; 7CMW ; 7KK2 ; 7KK3 ; 7KK4 ; 7KK5 ; 7KK6 ; 7ONR ; 7ONS ; 7ONT ; 7S68 ; 7S6H ; 7S6M ; 7S81 ; 7SCY ; 7SCZ ; 8HE7
EC Number
2.4.2.-; 2.4.2.30
Pfam ID
PF00533 ; PF21728 ; PF08063 ; PF00644 ; PF02877 ; PF05406 ; PF00645
Sequence
MAESSDKLYRVEYAKSGRASCKKCSESIPKDSLRMAIMVQSPMFDGKVPHWYHFSCFWKV
GHSIRHPDVEVDGFSELRWDDQQKVKKTAEAGGVTGKGQDGIGSKAEKTLGDFAAEYAKS
NRSTCKGCMEKIEKGQVRLSKKMVDPEKPQLGMIDRWYHPGCFVKNREELGFRPEYSASQ
LKGFSLLATEDKEALKKQLPGVKSEGKRKGDEVDGVDEVAKKKSKKEKDKDSKLEKALKA
QNDLIWNIKDELKKVCSTNDLKELLIFNKQQVPSGESAILDRVADGMVFGALLPCEECSG
QLVFKSDAYYCTGDVTAWTKCMVKTQTPNRKEWVTPKEFREISYLKKLKVKKQDRIFPPE
TSASVAATPPPSTASAPAAVNSSASADKPLSNMKILTLGKLSRNKDEVKAMIEKLGGKLT
GTANKASLCISTKKEVEKMNKKMEEVKEANIRVVSEDFLQDVSASTKSLQELFLAHILSP
WGAEVKAEPVEVVAPRGKSGAALSKKSKGQVKEEGINKSEKRMKLTLKGGAAVDPDSGLE
HSAHVLEKGGKVFSATLGLVDIVKGTNSYYKLQLLEDDKENRYWIFRSWGRVGTVIGSNK
LEQMPSKEDAIEHFMKLYEEKTGNAWHSKNFTKYPKKFYPLEIDYGQDEEAVKKLTVNPG
TKSKLPKPVQDLIKMIFDVESMKKAMVEYEIDLQKMPLGKLSKRQIQAAYSILSEVQQAV
SQGSSDSQILDLSNRFYTLIPHDFGMKKPPLLNNADSVQAKVEMLDNLLDIEVAYSLLRG
GSDDSSKDPIDVNYEKLKTDIKVVDRDSEEAEIIRKYVKNTHATTHNAYDLEVIDIFKIE
REGECQRYKPFKQLHNRRLLWHGSRTTNFAGILSQGLRIAPPEAPVTGYMFGKGIYFADM
VSKSANYCHTSQGDPIGLILLGEVALGNMYELKHASHISKLPKGKHSVKGLGKTTPDPSA
NISLDGVDVPLGTGISSGVNDTSLLYNEYIVYDIAQVNLKYLLKLKFNFKTSLW
Function
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair. Mediates glutamate, aspartate, serine, histidine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units. Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1. Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site. Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1. Following interaction with NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; NMNAT1 confers glutamate and aspartate specificity. PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr and H3S10ADPr), thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks. HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP1 in order to limit the length of poly-ADP-ribose chains. In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation. Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR, RPA1 and NFAT5. In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. PARP1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair. In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity. Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II. Acts both as a positive and negative regulator of transcription elongation, depending on the context. Acts as a positive regulator of transcription elongation by mediating poly-ADP-ribosylation of NELFE, preventing RNA-binding activity of NELFE and relieving transcription pausing. Acts as a negative regulator of transcription elongation in response to DNA damage by catalyzing poly-ADP-ribosylation of CCNT1, disrupting the phase separation activity of CCNT1 and subsequent activation of CDK9. Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression. Poly-ADP-ribose chains generated by PARP1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos. Also acts as a negative regulator of the cGAS-STING pathway. Acts by mediating poly-ADP-ribosylation of CGAS: PARP1 translocates into the cytosol following phosphorylation by PRKDC and catalyzes poly-ADP-ribosylation and inactivation of CGAS. Acts as a negative regulator of adipogenesis: catalyzes poly-ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) following interaction with NMNAT1, inhibiting phosphorylation of H2B at 'Ser-36' (H2BS36ph), thereby blocking expression of pro-adipogenetic genes. Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming ; [Poly [ADP-ribose] polymerase 1, processed C-terminus]: Promotes AIFM1-mediated apoptosis. This form, which translocates into the cytoplasm following cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis, is auto-poly-ADP-ribosylated and serves as a poly-ADP-ribose carrier to induce AIFM1-mediated apoptosis ; [Poly [ADP-ribose] polymerase 1, processed N-terminus]: This cleavage form irreversibly binds to DNA breaks and interferes with DNA repair, promoting DNA damage-induced apoptosis.
KEGG Pathway
Base excision repair (hsa03410 )
NF-kappa B sig.ling pathway (hsa04064 )
Apoptosis (hsa04210 )
Necroptosis (hsa04217 )
Diabetic cardiomyopathy (hsa05415 )
Reactome Pathway
vRNA Synthesis (R-HSA-192814 )
Downregulation of SMAD2/3 (R-HSA-2173795 )
SUMOylation of DNA damage response and repair proteins (R-HSA-3108214 )
HDR through MMEJ (alt-NHEJ) (R-HSA-5685939 )
DNA Damage Recognition in GG-NER (R-HSA-5696394 )
Formation of Incision Complex in GG-NER (R-HSA-5696395 )
Dual Incision in GG-NER (R-HSA-5696400 )
POLB-Dependent Long Patch Base Excision Repair (R-HSA-110362 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 3 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Zalcitabine DMH7MUV Approved Poly polymerase 1 (PARP1) increases the Cardiotoxicity ADR of Zalcitabine. [98]
Floxuridine DM04LR2 Approved Poly polymerase 1 (PARP1) decreases the response to substance of Floxuridine. [99]
UCN-01 DMUNJZB Phase 2 Poly polymerase 1 (PARP1) decreases the response to substance of UCN-01. [100]
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This DOT Affected the Regulation of Drug Effects of 3 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Nicotinamide mononucleotide DMW1LKP Preclinical Poly polymerase 1 (PARP1) affects the abundance of Nicotinamide mononucleotide. [101]
Serotonin DMOFCRY Investigative Poly polymerase 1 (PARP1) affects the abundance of Serotonin. [102]
Nicotinamide-Adenine-Dinucleotide DM9LRKB Investigative Poly polymerase 1 (PARP1) affects the abundance of Nicotinamide-Adenine-Dinucleotide. [103]
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30 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Poly polymerase 1 (PARP1). [1]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Poly polymerase 1 (PARP1). [2]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Poly polymerase 1 (PARP1). [3]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Poly polymerase 1 (PARP1). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Poly polymerase 1 (PARP1). [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the activity of Poly polymerase 1 (PARP1). [6]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Poly polymerase 1 (PARP1). [8]
Arsenic DMTL2Y1 Approved Arsenic decreases the expression of Poly polymerase 1 (PARP1). [9]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Poly polymerase 1 (PARP1). [10]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Poly polymerase 1 (PARP1). [12]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the activity of Poly polymerase 1 (PARP1). [13]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Poly polymerase 1 (PARP1). [15]
Marinol DM70IK5 Approved Marinol decreases the expression of Poly polymerase 1 (PARP1). [18]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Poly polymerase 1 (PARP1). [19]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Poly polymerase 1 (PARP1). [20]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Poly polymerase 1 (PARP1). [21]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Poly polymerase 1 (PARP1). [23]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of Poly polymerase 1 (PARP1). [24]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Poly polymerase 1 (PARP1). [25]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Poly polymerase 1 (PARP1). [28]
Irinotecan DMP6SC2 Approved Irinotecan increases the expression of Poly polymerase 1 (PARP1). [33]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Poly polymerase 1 (PARP1). [15]
Mitomycin DMH0ZJE Approved Mitomycin increases the activity of Poly polymerase 1 (PARP1). [38]
Sulindac DM2QHZU Approved Sulindac increases the activity of Poly polymerase 1 (PARP1). [44]
Benzatropine DMF7EXL Approved Benzatropine decreases the expression of Poly polymerase 1 (PARP1). [47]
Cholecalciferol DMGU74E Approved Cholecalciferol affects the expression of Poly polymerase 1 (PARP1). [61]
Isoproterenol DMK7MEY Approved Isoproterenol decreases the expression of Poly polymerase 1 (PARP1). [64]
Warfarin DMJYCVW Approved Warfarin increases the expression of Poly polymerase 1 (PARP1). [69]
Olaparib DM8QB1D Approved Olaparib decreases the activity of Poly polymerase 1 (PARP1). [88]
Acitretin DM8BKU9 Approved Acitretin increases the activity of Poly polymerase 1 (PARP1). [94]
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⏷ Show the Full List of 30 Drug(s)
68 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Estradiol DMUNTE3 Approved Estradiol increases the cleavage of Poly polymerase 1 (PARP1). [7]
Temozolomide DMKECZD Approved Temozolomide increases the cleavage of Poly polymerase 1 (PARP1). [11]
Vorinostat DMWMPD4 Approved Vorinostat increases the cleavage of Poly polymerase 1 (PARP1). [14]
Methotrexate DM2TEOL Approved Methotrexate increases the cleavage of Poly polymerase 1 (PARP1). [16]
Dexamethasone DMMWZET Approved Dexamethasone increases the cleavage of Poly polymerase 1 (PARP1). [22]
Bortezomib DMNO38U Approved Bortezomib increases the cleavage of Poly polymerase 1 (PARP1). [26]
Troglitazone DM3VFPD Approved Troglitazone increases the cleavage of Poly polymerase 1 (PARP1). [27]
Ethanol DMDRQZU Approved Ethanol increases the cleavage of Poly polymerase 1 (PARP1). [29]
Cytarabine DMZD5QR Approved Cytarabine increases the degradation of Poly polymerase 1 (PARP1). [30]
Aspirin DM672AH Approved Aspirin increases the cleavage of Poly polymerase 1 (PARP1). [31]
Etoposide DMNH3PG Approved Etoposide increases the cleavage of Poly polymerase 1 (PARP1). [32]
Paclitaxel DMLB81S Approved Paclitaxel increases the cleavage of Poly polymerase 1 (PARP1). [34]
Dasatinib DMJV2EK Approved Dasatinib increases the cleavage of Poly polymerase 1 (PARP1). [35]
DTI-015 DMXZRW0 Approved DTI-015 increases the cleavage of Poly polymerase 1 (PARP1). [36]
Indomethacin DMSC4A7 Approved Indomethacin increases the cleavage of Poly polymerase 1 (PARP1). [37]
Simvastatin DM30SGU Approved Simvastatin increases the cleavage of Poly polymerase 1 (PARP1). [39]
Topotecan DMP6G8T Approved Topotecan increases the cleavage of Poly polymerase 1 (PARP1). [40]
Gemcitabine DMSE3I7 Approved Gemcitabine increases the cleavage of Poly polymerase 1 (PARP1). [41]
Cyclophosphamide DM4O2Z7 Approved Cyclophosphamide increases the cleavage of Poly polymerase 1 (PARP1). [42]
Mifepristone DMGZQEF Approved Mifepristone increases the cleavage of Poly polymerase 1 (PARP1). [43]
Alitretinoin DMME8LH Approved Alitretinoin increases the cleavage of Poly polymerase 1 (PARP1). [46]
Methamphetamine DMPM4SK Approved Methamphetamine decreases the cleavage of Poly polymerase 1 (PARP1). [48]
Daunorubicin DMQUSBT Approved Daunorubicin increases the cleavage of Poly polymerase 1 (PARP1). [49]
Acocantherin DM7JT24 Approved Acocantherin increases the cleavage of Poly polymerase 1 (PARP1). [50]
Thalidomide DM70BU5 Approved Thalidomide increases the cleavage of Poly polymerase 1 (PARP1). [51]
Colchicine DM2POTE Approved Colchicine increases the cleavage of Poly polymerase 1 (PARP1). [52]
Enzalutamide DMGL19D Approved Enzalutamide decreases the cleavage of Poly polymerase 1 (PARP1). [53]
Sorafenib DMS8IFC Approved Sorafenib increases the cleavage of Poly polymerase 1 (PARP1). [54]
Ursodeoxycholic acid DMCUT21 Approved Ursodeoxycholic acid increases the cleavage of Poly polymerase 1 (PARP1). [55]
Gefitinib DM15F0X Approved Gefitinib increases the cleavage of Poly polymerase 1 (PARP1). [56]
Imatinib DM7RJXL Approved Imatinib increases the cleavage of Poly polymerase 1 (PARP1). [57]
Ritonavir DMU764S Approved Ritonavir increases the cleavage of Poly polymerase 1 (PARP1). [58]
Chenodiol DMQ8JIK Approved Chenodiol increases the cleavage of Poly polymerase 1 (PARP1). [59]
Docetaxel DMDI269 Approved Docetaxel increases the cleavage of Poly polymerase 1 (PARP1). [60]
Dopamine DMPGUCF Approved Dopamine increases the cleavage of Poly polymerase 1 (PARP1). [62]
Nitric Oxide DM1RBYG Approved Nitric Oxide increases the cleavage of Poly polymerase 1 (PARP1). [63]
Lovastatin DM9OZWQ Approved Lovastatin increases the cleavage of Poly polymerase 1 (PARP1). [65]
Deoxycholic acid DM3GYAL Approved Deoxycholic acid increases the cleavage of Poly polymerase 1 (PARP1). [66]
Glucosamine DM4ZLFD Approved Glucosamine increases the cleavage of Poly polymerase 1 (PARP1). [67]
Artesunate DMR27C8 Approved Artesunate increases the cleavage of Poly polymerase 1 (PARP1). [68]
Orlistat DMRJSP8 Approved Orlistat increases the cleavage of Poly polymerase 1 (PARP1). [70]
Eicosapentaenoic acid/docosa-hexaenoic acid DMMUCG4 Approved Eicosapentaenoic acid/docosa-hexaenoic acid increases the cleavage of Poly polymerase 1 (PARP1). [71]
2-deoxyglucose DMIAHVU Approved 2-deoxyglucose increases the cleavage of Poly polymerase 1 (PARP1). [72]
Dihydroxyacetone DMM1LG2 Approved Dihydroxyacetone increases the cleavage of Poly polymerase 1 (PARP1). [73]
Penicillamine DM40EF6 Approved Penicillamine increases the cleavage of Poly polymerase 1 (PARP1). [74]
Crizotinib DM4F29C Approved Crizotinib increases the cleavage of Poly polymerase 1 (PARP1). [75]
Ciprofloxacin XR DM2NLS9 Approved Ciprofloxacin XR increases the cleavage of Poly polymerase 1 (PARP1). [76]
Cantharidin DMBP5N3 Approved Cantharidin increases the cleavage of Poly polymerase 1 (PARP1). [77]
Omeprazole DM471KJ Approved Omeprazole increases the cleavage of Poly polymerase 1 (PARP1). [78]
Romidepsin DMT5GNL Approved Romidepsin increases the cleavage of Poly polymerase 1 (PARP1). [79]
Nilotinib DM7HXWT Approved Nilotinib increases the cleavage of Poly polymerase 1 (PARP1). [80]
Lapatinib DM3BH1Y Approved Lapatinib increases the cleavage of Poly polymerase 1 (PARP1). [81]
Trovafloxacin DM6AN32 Approved Trovafloxacin increases the cleavage of Poly polymerase 1 (PARP1). [82]
Busulfan DMXYJ9C Approved Busulfan increases the cleavage of Poly polymerase 1 (PARP1). [83]
Imipramine DM2NUH3 Approved Imipramine increases the cleavage of Poly polymerase 1 (PARP1). [84]
Epinephrine DM3KJBC Approved Epinephrine decreases the cleavage of Poly polymerase 1 (PARP1). [85]
Clomipramine DMINRKW Approved Clomipramine increases the cleavage of Poly polymerase 1 (PARP1). [84]
Citalopram DM2G9AE Approved Citalopram increases the cleavage of Poly polymerase 1 (PARP1). [84]
Ropivacaine DMSPJG2 Approved Ropivacaine increases the cleavage of Poly polymerase 1 (PARP1). [86]
AC220 DM8Y4JS Approved AC220 increases the cleavage of Poly polymerase 1 (PARP1). [87]
Osimertinib DMRJLAT Approved Osimertinib increases the cleavage of Poly polymerase 1 (PARP1). [89]
Pamidronate DMB4AVP Approved Pamidronate increases the cleavage of Poly polymerase 1 (PARP1). [90]
Cladribine DM3JDRP Approved Cladribine increases the cleavage of Poly polymerase 1 (PARP1). [91]
Furazolidone DM3P6V7 Approved Furazolidone increases the cleavage of Poly polymerase 1 (PARP1). [92]
Emetine DMCT2YF Approved Emetine increases the cleavage of Poly polymerase 1 (PARP1). [93]
Bendamustine hydrochloride DMFH15Z Approved Bendamustine hydrochloride increases the cleavage of Poly polymerase 1 (PARP1). [95]
Desloratadine DM56YN7 Approved Desloratadine increases the cleavage of Poly polymerase 1 (PARP1). [96]
Regorafenib DMHSY1I Approved Regorafenib increases the cleavage of Poly polymerase 1 (PARP1). [97]
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⏷ Show the Full List of 68 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Decitabine DMQL8XJ Approved Decitabine decreases the methylation of Poly polymerase 1 (PARP1). [17]
Capsaicin DMGMF6V Approved Capsaicin increases the ADP-ribosylation of Poly polymerase 1 (PARP1). [45]
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