General Information of Drug Off-Target (DOT) (ID: OTPQX849)

DOT Name DNA-directed RNA polymerase III subunit RPC3 (POLR3C)
Synonyms RNA polymerase III subunit C3; DNA-directed RNA polymerase III subunit C; RNA polymerase III 62 kDa subunit; RPC62
Gene Name POLR3C
Related Disease
Gout ( )
UniProt ID
RPC3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2XUB; 2XV4; 5AFQ; 7A6H; 7AE1; 7AE3; 7AEA; 7AST; 7D58; 7D59; 7DN3; 7DU2; 7FJI; 7FJJ; 8ITY; 8IUE; 8IUH
Pfam ID
PF08221 ; PF05645 ; PF20912
Sequence
MTQAEIKLCSLLLQEHFGEIVEKIGVHLIRTGSQPLRVIAHDTGTSLDQVKKALCVLVQH
NLVSYQVHKRGVVEYEAQCSRVLRMLRYPRYIYTTKTLYSDTGELIVEELLLNGKLTMSA
VVKKVADRLTETMEDGKTMDYAEVSNTFVRLADTHFVQRCPSVPTTENSDPGPPPPAPTL
VINEKDMYLVPKLSLIGKGKRRRSSDEDAAGEPKAKRPKYTTDNKEPIPDDGIYWQANLD
RFHQHFRDQAIVSAVANRMDQTSSEIVRTMLRMSEITTSSSAPFTQPLSSNEIFRSLPVG
YNISKQVLDQYLTLLADDPLEFVGKSGDSGGGMYVINLHKALASLATATLESVVQERFGS
RCARIFRLVLQKKHIEQKQVEDFAMIPAKEAKDMLYKMLSENFMSLQEIPKTPDHAPSRT
FYLYTVNILSAARMLLHRCYKSIANLIERRQFETKENKRLLEKSQRVEAIIASMQATGAE
EAQLQEIEEMITAPERQQLETLKRNVNKLDASEIQVDETIFLLESYIECTMKRQ
Function
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III (Pol III) which synthesizes small non-coding RNAs including 5S rRNA, snRNAs, tRNAs and miRNAs from at least 500 distinct genomic loci. Part of POLR3C/RPC3-POLR3F/RPC6-POLR3G/RPC7 heterotrimer, coordinates the dynamics of Pol III stalk and clamp modules during the transition from apo to elongation state. Pol III plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as a nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF-kappa-B through the RIG-I pathway. Preferentially binds single-stranded DNA (ssDNA) in a sequence-independent manner.
KEGG Pathway
R. polymerase (hsa03020 )
Cytosolic D.-sensing pathway (hsa04623 )
Reactome Pathway
RNA Polymerase III Chain Elongation (R-HSA-73780 )
RNA Polymerase III Transcription Termination (R-HSA-73980 )
RNA Polymerase III Abortive And Retractive Initiation (R-HSA-749476 )
RNA Polymerase III Transcription Initiation From Type 1 Promoter (R-HSA-76061 )
RNA Polymerase III Transcription Initiation From Type 2 Promoter (R-HSA-76066 )
RNA Polymerase III Transcription Initiation From Type 3 Promoter (R-HSA-76071 )
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
Gout DISHC0U7 Strong Genetic Variation [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of DNA-directed RNA polymerase III subunit RPC3 (POLR3C). [2]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of DNA-directed RNA polymerase III subunit RPC3 (POLR3C). [3]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of DNA-directed RNA polymerase III subunit RPC3 (POLR3C). [4]
Quercetin DM3NC4M Approved Quercetin increases the expression of DNA-directed RNA polymerase III subunit RPC3 (POLR3C). [5]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of DNA-directed RNA polymerase III subunit RPC3 (POLR3C). [6]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of DNA-directed RNA polymerase III subunit RPC3 (POLR3C). [7]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of DNA-directed RNA polymerase III subunit RPC3 (POLR3C). [8]
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⏷ Show the Full List of 6 Drug(s)

References

1 Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
2 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
3 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
4 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
5 Quantitative proteomic analysis of HepG2 cells treated with quercetin suggests IQGAP1 involved in quercetin-induced regulation of cell proliferation and migration. OMICS. 2009 Apr;13(2):93-103. doi: 10.1089/omi.2008.0075.
6 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
7 Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
8 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.