Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKGOZ49)

DOT Name RNA polymerase I-specific transcription initiation factor RRN3 (RRN3)
Synonyms Transcription initiation factor IA; TIF-IA
Gene Name RRN3
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Multiple sclerosis ( )
Relapsing-remitting multiple sclerosis ( )
Schizophrenia ( )
Gallbladder cancer ( )
Gallbladder carcinoma ( )
Advanced cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Nervous system inflammation ( )
UniProt ID
RRN3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7OBA
Pfam ID
PF05327
Sequence
MAAPLLHTRLPGDAAASSSAVKKLGASRTGISNMRALENDFFNSPPRKTVRFGGTVTEVL
LKYKKGETNDFELLKNQLLDPDIKDDQIINWLLEFRSSIMYLTKDFEQLISIILRLPWLN
RSQTVVEEYLAFLGNLVSAQTVFLRPCLSMIASHFVPPRVIIKEGDVDVSDSDDEDDNLP
ANFDTCHRALQIIARYVPSTPWFLMPILVEKFPFVRKSERTLECYVHNLLRISVYFPTLR
HEILELIIEKLLKLDVNASRQGIEDAEETATQTCGGTDSTEGLFNMDEDEETEHETKAGP
ERLDQMVHPVAERLDILMSLVLSYMKDVCYVDGKVDNGKTKDLYRDLINIFDKLLLPTHA
SCHVQFFMFYLCSFKLGFAEAFLEHLWKKLQDPSNPAIIRQAAGNYIGSFLARAKFIPLI
TVKSCLDLLVNWLHIYLNNQDSGTKAFCDVALHGPFYSACQAVFYTFVFRHKQLLSGNLK
EGLQYLQSLNFERIVMSQLNPLKICLPSVVNFFAAITNKYQLVFCYTIIERNNRQMLPVI
RSTAGGDSVQICTNPLDTFFPFDPCVLKRSKKFIDPIYQVWEDMSAEELQEFKKPMKKDI
VEDEDDDFLKGEVPQNDTVIGITPSSFDTHFRSPSSSVGSPPVLYMQPSPL
Function Required for efficient transcription initiation by RNA polymerase I (Pol I). Required for the formation of the competent pre-initiation complex (PIC).
Reactome Pathway
RNA Polymerase I Promoter Escape (R-HSA-73772 )
RNA Polymerase I Transcription Initiation (R-HSA-73762 )

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Altered Expression [1]
Breast carcinoma DIS2UE88 Strong Altered Expression [1]
Multiple sclerosis DISB2WZI Strong Biomarker [2]
Relapsing-remitting multiple sclerosis DISSXFCF Strong Altered Expression [3]
Schizophrenia DISSRV2N Strong Genetic Variation [4]
Gallbladder cancer DISXJUAF Disputed Altered Expression [5]
Gallbladder carcinoma DISD6ACL Disputed Altered Expression [5]
Advanced cancer DISAT1Z9 Limited Altered Expression [6]
Lung cancer DISCM4YA Limited Biomarker [7]
Lung carcinoma DISTR26C Limited Biomarker [7]
Nervous system inflammation DISB3X5A Limited Altered Expression [8]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of RNA polymerase I-specific transcription initiation factor RRN3 (RRN3). [9]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of RNA polymerase I-specific transcription initiation factor RRN3 (RRN3). [10]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of RNA polymerase I-specific transcription initiation factor RRN3 (RRN3). [11]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of RNA polymerase I-specific transcription initiation factor RRN3 (RRN3). [15]
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5 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Estradiol DMUNTE3 Approved Estradiol decreases the phosphorylation of RNA polymerase I-specific transcription initiation factor RRN3 (RRN3). [12]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of RNA polymerase I-specific transcription initiation factor RRN3 (RRN3). [13]
G1 DMTV42K Phase 1/2 G1 decreases the phosphorylation of RNA polymerase I-specific transcription initiation factor RRN3 (RRN3). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of RNA polymerase I-specific transcription initiation factor RRN3 (RRN3). [14]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of RNA polymerase I-specific transcription initiation factor RRN3 (RRN3). [16]
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References

1 Mammary epithelial morphogenesis and early breast cancer. Evidence of involvement of basal components of the RNA Polymerase I transcription machinery.Cell Cycle. 2016 Sep 16;15(18):2515-26. doi: 10.1080/15384101.2016.1215385. Epub 2016 Aug 2.
2 Polymerase-1 pathway activation in acute multiple sclerosis relapse.Autoimmun Rev. 2018 Dec;17(12):1235-1239. doi: 10.1016/j.autrev.2018.07.006. Epub 2018 Oct 11.
3 Suppressed RNA-polymerase 1 pathway is associated with benign multiple sclerosis.PLoS One. 2012;7(10):e46871. doi: 10.1371/journal.pone.0046871. Epub 2012 Oct 12.
4 Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
5 Circular RNA circERBB2 promotes gallbladder cancer progression by regulating PA2G4-dependent rDNA transcription.Mol Cancer. 2019 Nov 21;18(1):166. doi: 10.1186/s12943-019-1098-8.
6 LKB1 promotes cell survival by modulating TIF-IA-mediated pre-ribosomal RNA synthesis under uridine downregulated conditions.Oncotarget. 2016 Jan 19;7(3):2519-31. doi: 10.18632/oncotarget.6224.
7 TIF-IA: An oncogenic target of pre-ribosomal RNA synthesis.Biochim Biophys Acta. 2016 Dec;1866(2):189-196. doi: 10.1016/j.bbcan.2016.09.003. Epub 2016 Sep 15.
8 Experimental Autoimmune Encephalomyelitis Ameliorated by Passive Transfer of Polymerase 1-Silenced MOG35-55 Lymphatic Node Cells: Verification of a Novel Therapeutic Approach in Multiple Sclerosis.Neuromolecular Med. 2017 Sep;19(2-3):406-412. doi: 10.1007/s12017-017-8456-8. Epub 2017 Jul 28.
9 Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
10 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 The G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Nuclear Estrogen Receptor Activity and Stimulates Novel Phosphoproteomic Signatures. Toxicol Sci. 2016 Jun;151(2):434-46. doi: 10.1093/toxsci/kfw057. Epub 2016 Mar 29.
13 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
14 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
15 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
16 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.