Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIC02RT)

• DOT Name: mRNA cap guanine-N7 methyltransferase (RNMT)
• Synonyms: EC 2.1.1.56; RG7MT1; mRNA (guanine-N(7))-methyltransferase; mRNA cap methyltransferase; hCMT1; hMet; hcm1p
• Gene Name: RNMT
• UniProt ID: MCES_HUMAN
• PDB ID: 3BGV; 3EPP; 5E8J; 5E9J; 5E9W
• EC Number: 2.1.1.56
• Pfam ID: PF03291
• Sequence:
  MANSAKAEEYEKMSLEQAKASVNSETESSFNINENTTASGTGLSEKTSVCRQVDIARKRK
  EFEDDLVKESSSCGKDTPSKKRKLDPEIVPEEKDCGDAEGNSKKRKRETEDVPKDKSSTG
  DGTQNKRKIALEDVPEKQKNLEEGHSSTVAAHYNELQEVGLEKRSQSRIFYLRNFNNWMK
  SVLIGEFLEKVRQKKKRDITVLDLGCGKGGDLLKWKKGRINKLVCTDIADVSVKQCQQRY
  EDMKNRRDSEYIFSAEFITADSSKELLIDKFRDPQMCFDICSCQFVCHYSFESYEQADMM
  LRNACERLSPGGYFIGTTPNSFELIRRLEASETESFGNEIYTVKFQKKGDYPLFGCKYDF
  NLEGVVDVPEFLVYFPLLNEMAKKYNMKLVYKKTFLEFYEEKIKNNENKMLLKRMQALEP
  YPANESSKLVSEKVDDYEHAAKYMKNSQVRLPLGTLSKSEWEATSIYLVFAFEKQQ
• Function: Catalytic subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs. Binds RNA containing 5'-terminal GpppC.
• Tissue Specificity: Widely expressed.
• KEGG Pathway: mR. surveillance pathway (hsa03015)
• Reactome Pathway:
  mRNA Capping (R-HSA-72086)
  RNA Pol II CTD phosphorylation and interaction with CE (R-HSA-77075)
  RNA Pol II CTD phosphorylation and interaction with CE during HIV infection (R-HSA-167160)
• BioCyc Pathway: MetaCyc:HS02296-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

12 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 mRNA cap guanine-N7 methyltransferase (RNMT).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of mRNA cap guanine-N7 methyltransferase (RNMT).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of mRNA cap guanine-N7 methyltransferase (RNMT).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of mRNA cap guanine-N7 methyltransferase (RNMT).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of mRNA cap guanine-N7 methyltransferase (RNMT).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of mRNA cap guanine-N7 methyltransferase (RNMT).	[6]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of mRNA cap guanine-N7 methyltransferase (RNMT).	[3]
Lithium	DMZ3OU6	Phase 2	Lithium increases the expression of mRNA cap guanine-N7 methyltransferase (RNMT).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of mRNA cap guanine-N7 methyltransferase (RNMT).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of mRNA cap guanine-N7 methyltransferase (RNMT).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of mRNA cap guanine-N7 methyltransferase (RNMT).	[12]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of mRNA cap guanine-N7 methyltransferase (RNMT).	[13]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of mRNA cap guanine-N7 methyltransferase (RNMT).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of mRNA cap guanine-N7 methyltransferase (RNMT).	[9]
1,6-hexamethylene diisocyanate	DMLB3RT	Investigative	1,6-hexamethylene diisocyanate increases the methylation of mRNA cap guanine-N7 methyltransferase (RNMT).	[14]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] 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.
• [3] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Effect of mood stabilizers on gene expression in lymphoblastoid cells. J Neural Transm (Vienna). 2010 Feb;117(2):155-64.
• [8] 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.
• [9] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [10] 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.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
• [14] DNA methylation modifies urine biomarker levels in 1,6-hexamethylene diisocyanate exposed workers: a pilot study. Toxicol Lett. 2014 Dec 1;231(2):217-26. doi: 10.1016/j.toxlet.2014.10.024. Epub 2014 Oct 22.