Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHZ1RIA)

DOT Name Proliferating cell nuclear antigen (PCNA)
Synonyms PCNA; Cyclin
Gene Name PCNA
Related Disease
Ataxia-telangiectasia-like disorder 2 ( )
UniProt ID
PCNA_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1AXC ; 1U76 ; 1U7B ; 1UL1 ; 1VYJ ; 1VYM ; 1W60 ; 2ZVK ; 2ZVL ; 2ZVM ; 3JA9 ; 3P87 ; 3TBL ; 3VKX ; 3WGW ; 4D2G ; 4RJF ; 4ZTD ; 5E0T ; 5E0U ; 5E0V ; 5IY4 ; 5MAV ; 5MLO ; 5MLW ; 5MOM ; 5YCO ; 5YD8 ; 6CBI ; 6EHT ; 6FCM ; 6FCN ; 6GIS ; 6GWS ; 6HVO ; 6K3A ; 6QC0 ; 6QCG ; 6S1M ; 6S1N ; 6S1O ; 6TNY ; 6TNZ ; 6VVO ; 7EFA ; 7KQ0 ; 7KQ1 ; 7M5L ; 7M5M ; 7M5N ; 7NV0 ; 7NV1 ; 7QNZ ; 7QO1 ; 8B8T ; 8COB ; 8E84 ; 8F5Q ; 8GL9 ; 8GLA
Pfam ID
PF02747 ; PF00705
Sequence
MFEARLVQGSILKKVLEALKDLINEACWDISSSGVNLQSMDSSHVSLVQLTLRSEGFDTY
RCDRNLAMGVNLTSMSKILKCAGNEDIITLRAEDNADTLALVFEAPNQEKVSDYEMKLMD
LDVEQLGIPEQEYSCVVKMPSGEFARICRDLSHIGDAVVISCAKDGVKFSASGELGNGNI
KLSQTSNVDKEEEAVTIEMNEPVQLTFALRYLNFFTKATPLSSTVTLSMSADVPLVVEYK
IADMGHLKYYLAPKIEDEEGS
Function
Auxiliary protein of DNA polymerase delta and epsilon, is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.
KEGG Pathway
D. replication (hsa03030 )
Base excision repair (hsa03410 )
Nucleotide excision repair (hsa03420 )
Mismatch repair (hsa03430 )
Cell cycle (hsa04110 )
Tight junction (hsa04530 )
Hepatitis B (hsa05161 )
Reactome Pathway
Recognition of DNA damage by PCNA-containing replication complex (R-HSA-110314 )
Translesion Synthesis by POLH (R-HSA-110320 )
Transcription of E2F targets under negative control by DREAM complex (R-HSA-1362277 )
Polymerase switching on the C-strand of the telomere (R-HSA-174411 )
Processive synthesis on the C-strand of the telomere (R-HSA-174414 )
Telomere C-strand (Lagging Strand) Synthesis (R-HSA-174417 )
Removal of the Flap Intermediate from the C-strand (R-HSA-174437 )
SUMOylation of DNA replication proteins (R-HSA-4615885 )
Mismatch repair (MMR) directed by MSH2 (R-HSA-5358565 )
Mismatch repair (MMR) directed by MSH2 (R-HSA-5358606 )
PCNA-Dependent Long Patch Base Excision Repair (R-HSA-5651801 )
Translesion synthesis by POLK (R-HSA-5655862 )
Translesion synthesis by POLI (R-HSA-5656121 )
Termination of translesion DNA synthesis (R-HSA-5656169 )
HDR through Homologous Recombination (HRR) (R-HSA-5685942 )
Gap-filling DNA repair synthesis and ligation in GG-NER (R-HSA-5696397 )
Dual Incision in GG-NER (R-HSA-5696400 )
Dual incision in TC-NER (R-HSA-6782135 )
Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210 )
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest (R-HSA-6804114 )
Polymerase switching (R-HSA-69091 )
Removal of the Flap Intermediate (R-HSA-69166 )
Processive synthesis on the lagging strand (R-HSA-69183 )
G1/S-Specific Transcription (R-HSA-69205 )
E3 ubiquitin ligases ubiquitinate target proteins (R-HSA-8866654 )
Translesion synthesis by REV1 (R-HSA-110312 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Ataxia-telangiectasia-like disorder 2 DISFL9N4 Supportive 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
Sulforaphane DMQY3L0 Investigative Proliferating cell nuclear antigen (PCNA) affects the binding of Sulforaphane. [88]
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91 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 Proliferating cell nuclear antigen (PCNA). [2]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Proliferating cell nuclear antigen (PCNA). [3]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Proliferating cell nuclear antigen (PCNA). [4]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Proliferating cell nuclear antigen (PCNA). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Proliferating cell nuclear antigen (PCNA). [6]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Proliferating cell nuclear antigen (PCNA). [7]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Proliferating cell nuclear antigen (PCNA). [8]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Proliferating cell nuclear antigen (PCNA). [9]
Arsenic DMTL2Y1 Approved Arsenic increases the expression of Proliferating cell nuclear antigen (PCNA). [10]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Proliferating cell nuclear antigen (PCNA). [11]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Proliferating cell nuclear antigen (PCNA). [12]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Proliferating cell nuclear antigen (PCNA). [13]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Proliferating cell nuclear antigen (PCNA). [14]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Proliferating cell nuclear antigen (PCNA). [15]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Proliferating cell nuclear antigen (PCNA). [16]
Marinol DM70IK5 Approved Marinol increases the expression of Proliferating cell nuclear antigen (PCNA). [18]
Selenium DM25CGV Approved Selenium decreases the expression of Proliferating cell nuclear antigen (PCNA). [19]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Proliferating cell nuclear antigen (PCNA). [20]
Menadione DMSJDTY Approved Menadione decreases the expression of Proliferating cell nuclear antigen (PCNA). [21]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of Proliferating cell nuclear antigen (PCNA). [22]
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the expression of Proliferating cell nuclear antigen (PCNA). [8]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Proliferating cell nuclear antigen (PCNA). [23]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of Proliferating cell nuclear antigen (PCNA). [24]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Proliferating cell nuclear antigen (PCNA). [25]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Proliferating cell nuclear antigen (PCNA). [26]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of Proliferating cell nuclear antigen (PCNA). [27]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Proliferating cell nuclear antigen (PCNA). [28]
Paclitaxel DMLB81S Approved Paclitaxel decreases the expression of Proliferating cell nuclear antigen (PCNA). [29]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Proliferating cell nuclear antigen (PCNA). [30]
Nicotine DMWX5CO Approved Nicotine increases the expression of Proliferating cell nuclear antigen (PCNA). [31]
Piroxicam DMTK234 Approved Piroxicam decreases the expression of Proliferating cell nuclear antigen (PCNA). [32]
Malathion DMXZ84M Approved Malathion increases the expression of Proliferating cell nuclear antigen (PCNA). [33]
Indomethacin DMSC4A7 Approved Indomethacin decreases the expression of Proliferating cell nuclear antigen (PCNA). [34]
Mitomycin DMH0ZJE Approved Mitomycin increases the expression of Proliferating cell nuclear antigen (PCNA). [35]
Simvastatin DM30SGU Approved Simvastatin decreases the expression of Proliferating cell nuclear antigen (PCNA). [36]
Topotecan DMP6G8T Approved Topotecan decreases the expression of Proliferating cell nuclear antigen (PCNA). [37]
Fenofibrate DMFKXDY Approved Fenofibrate increases the expression of Proliferating cell nuclear antigen (PCNA). [38]
Palbociclib DMD7L94 Approved Palbociclib decreases the expression of Proliferating cell nuclear antigen (PCNA). [39]
Acocantherin DM7JT24 Approved Acocantherin decreases the expression of Proliferating cell nuclear antigen (PCNA). [40]
Bicalutamide DMZMSPF Approved Bicalutamide decreases the expression of Proliferating cell nuclear antigen (PCNA). [42]
Hydroxyurea DMOQVU9 Approved Hydroxyurea increases the expression of Proliferating cell nuclear antigen (PCNA). [35]
Hydrocortisone DMGEMB7 Approved Hydrocortisone decreases the expression of Proliferating cell nuclear antigen (PCNA). [43]
Nefazodone DM4ZS8M Approved Nefazodone decreases the expression of Proliferating cell nuclear antigen (PCNA). [44]
Propofol DMB4OLE Approved Propofol decreases the expression of Proliferating cell nuclear antigen (PCNA). [45]
Melatonin DMKWFBT Approved Melatonin decreases the expression of Proliferating cell nuclear antigen (PCNA). [46]
Ximelegatran DMU8ANS Approved Ximelegatran decreases the expression of Proliferating cell nuclear antigen (PCNA). [47]
Dihydroxyacetone DMM1LG2 Approved Dihydroxyacetone increases the expression of Proliferating cell nuclear antigen (PCNA). [48]
Methimazole DM25FL8 Approved Methimazole decreases the expression of Proliferating cell nuclear antigen (PCNA). [49]
Gamolenic acid DMQN30Z Approved Gamolenic acid decreases the expression of Proliferating cell nuclear antigen (PCNA). [50]
Nelfinavir mesylate DMFX6G8 Approved Nelfinavir mesylate decreases the expression of Proliferating cell nuclear antigen (PCNA). [51]
Epinephrine DM3KJBC Approved Epinephrine increases the expression of Proliferating cell nuclear antigen (PCNA). [52]
Fludarabine DMVRLT7 Approved Fludarabine increases the expression of Proliferating cell nuclear antigen (PCNA). [53]
Olaparib DM8QB1D Approved Olaparib decreases the expression of Proliferating cell nuclear antigen (PCNA). [54]
Cilostazol DMZMSCT Approved Cilostazol decreases the expression of Proliferating cell nuclear antigen (PCNA). [55]
Calcidiol DMN4CV5 Approved Calcidiol decreases the expression of Proliferating cell nuclear antigen (PCNA). [56]
Thiazolidinedione DMC1NBW Approved Thiazolidinedione decreases the expression of Proliferating cell nuclear antigen (PCNA). [57]
Meloxicam DM2AR7L Approved Meloxicam decreases the expression of Proliferating cell nuclear antigen (PCNA). [58]
OPC-34712 DMHG57U Approved OPC-34712 decreases the expression of Proliferating cell nuclear antigen (PCNA). [59]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Proliferating cell nuclear antigen (PCNA). [60]
Tamibarotene DM3G74J Phase 3 Tamibarotene affects the expression of Proliferating cell nuclear antigen (PCNA). [3]
Curcumin DMQPH29 Phase 3 Curcumin increases the expression of Proliferating cell nuclear antigen (PCNA). [61]
Fenretinide DMRD5SP Phase 3 Fenretinide decreases the expression of Proliferating cell nuclear antigen (PCNA). [62]
Coprexa DMA0WEK Phase 3 Coprexa decreases the expression of Proliferating cell nuclear antigen (PCNA). [63]
HMPL-004 DM29XGY Phase 3 HMPL-004 decreases the expression of Proliferating cell nuclear antigen (PCNA). [64]
Avastin+/-Tarceva DMA86FL Phase 3 Avastin+/-Tarceva decreases the expression of Proliferating cell nuclear antigen (PCNA). [65]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Proliferating cell nuclear antigen (PCNA). [66]
Afimoxifene DMFORDT Phase 2 Afimoxifene decreases the expression of Proliferating cell nuclear antigen (PCNA). [8]
Flavopiridol DMKSUOI Phase 2 Flavopiridol decreases the activity of Proliferating cell nuclear antigen (PCNA). [67]
INCB054329 DM7TZL0 Phase 1/2 INCB054329 decreases the expression of Proliferating cell nuclear antigen (PCNA). [54]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Proliferating cell nuclear antigen (PCNA). [68]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Proliferating cell nuclear antigen (PCNA). [69]
Ribavirin DMEYLH9 Phase 1 Trial Ribavirin decreases the expression of Proliferating cell nuclear antigen (PCNA). [70]
BETULINIC ACID DMBUI2A Phase 1 BETULINIC ACID decreases the expression of Proliferating cell nuclear antigen (PCNA). [71]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Proliferating cell nuclear antigen (PCNA). [72]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Proliferating cell nuclear antigen (PCNA). [73]
Beta-aminopropionitrile DMSJ2I6 Preclinical Beta-aminopropionitrile decreases the expression of Proliferating cell nuclear antigen (PCNA). [63]
EMBELIN DMFZO4Y Terminated EMBELIN decreases the expression of Proliferating cell nuclear antigen (PCNA). [74]
Coumarin DM0N8ZM Investigative Coumarin increases the expression of Proliferating cell nuclear antigen (PCNA). [76]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Proliferating cell nuclear antigen (PCNA). [77]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A decreases the expression of Proliferating cell nuclear antigen (PCNA). [78]
Glyphosate DM0AFY7 Investigative Glyphosate decreases the expression of Proliferating cell nuclear antigen (PCNA). [79]
Phencyclidine DMQBEYX Investigative Phencyclidine decreases the expression of Proliferating cell nuclear antigen (PCNA). [80]
Rapamycin Immunosuppressant Drug DM678IB Investigative Rapamycin Immunosuppressant Drug decreases the expression of Proliferating cell nuclear antigen (PCNA). [81]
Dibutyl phthalate DMEDGKO Investigative Dibutyl phthalate increases the expression of Proliferating cell nuclear antigen (PCNA). [82]
BRN-3548355 DM4KXT0 Investigative BRN-3548355 decreases the expression of Proliferating cell nuclear antigen (PCNA). [83]
Daidzein DMRFTJX Investigative Daidzein decreases the expression of Proliferating cell nuclear antigen (PCNA). [84]
N-nonylphenol DMH3OUX Investigative N-nonylphenol increases the expression of Proliferating cell nuclear antigen (PCNA). [82]
NORCANTHARIDIN DM9B6Y1 Investigative NORCANTHARIDIN decreases the expression of Proliferating cell nuclear antigen (PCNA). [85]
DIECKOL DMBCK4G Investigative DIECKOL decreases the expression of Proliferating cell nuclear antigen (PCNA). [86]
Tyrphostin Ag-1478 DM87ZIH Investigative Tyrphostin Ag-1478 decreases the expression of Proliferating cell nuclear antigen (PCNA). [37]
9-hydroxyoctadecadienoic acid DM0FWNJ Investigative 9-hydroxyoctadecadienoic acid decreases the expression of Proliferating cell nuclear antigen (PCNA). [87]
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⏷ Show the Full List of 91 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 affects the methylation of Proliferating cell nuclear antigen (PCNA). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Proliferating cell nuclear antigen (PCNA). [75]
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1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
Liothyronine DM6IR3P Approved Liothyronine affects the binding of Proliferating cell nuclear antigen (PCNA). [41]
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References

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