Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG0N8GA)

• DOT Name: Cap-specific mRNA (CMTR1)
• Synonyms: nucleoside-2'-O-)-methyltransferase 1 (EC 2.1.1.57; Cap methyltransferase 1; Cap1 2'O-ribose methyltransferase 1; MTr1; hMTr1; FtsJ methyltransferase domain-containing protein 2; Interferon-stimulated gene 95 kDa protein; ISG95
• Gene Name: CMTR1
• Related Disease:
  Beckwith-Wiedemann syndrome
  Breast cancer
  Breast carcinoma
  Rhabdomyosarcoma
• UniProt ID: CMTR1_HUMAN
• PDB ID: 4N48; 4N49; 4N4A; 8P4E; 8P4F
• EC Number: 2.1.1.57
• Pfam ID: PF01728 ; PF01585
• Sequence:
  MKRRTDPECTAPIKKQKKRVAELALSLSSTSDDEPPSSVSHGAKASTTSLSGSDSETEGK
  QHSSDSFDDAFKADSLVEGTSSRYSMYNSVSQKLMAKMGFREGEGLGKYSQGRKDIVEAS
  SQKGRRGLGLTLRGFDQELNVDWRDEPEPSACEQVSWFPECTTEIPDTQEMSDWMVVGKR
  KMIIEDETEFCGEELLHSVLQCKSVFDVLDGEEMRRARTRANPYEMIRGVFFLNRAAMKM
  ANMDFVFDRMFTNPRDSYGKPLVKDREAELLYFADVCAGPGGFSEYVLWRKKWHAKGFGM
  TLKGPNDFKLEDFYSASSELFEPYYGEGGIDGDGDITRPENISAFRNFVLDNTDRKGVHF
  LMADGGFSVEGQENLQEILSKQLLLCQFLMALSIVRTGGHFICKTFDLFTPFSVGLVYLL
  YCCFERVCLFKPITSRPANSERYVVCKGLKVGIDDVRDYLFAVNIKLNQLRNTDSDVNLV
  VPLEVIKGDHEFTDYMIRSNESHCSLQIKALAKIHAFVQDTTLSEPRQAEIRKECLRLWG
  IPDQARVAPSSSDPKSKFFELIQGTEIDIFSYKPTLLTSKTLEKIRPVFDYRCMVSGSEQ
  KFLIGLGKSQIYTWDGRQSDRWIKLDLKTELPRDTLLSVEIVHELKGEGKAQRKISAIHI
  LDVLVLNGTDVREQHFNQRIQLAEKFVKAVSKPSRPDMNPIRVKEVYRLEEMEKIFVRLE
  MKIIKGSSGTPKLSYTGRDDRHFVPMGLYIVRTVNEPWTMGFSKSFKKKFFYNKKTKDST
  FDLPADSIAPFHICYYGRLFWEWGDGIRVHDSQKPQDQDKLSKEDVLSFIQMHRA
• Function: S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap1 2'-O-ribose methylation to the 5'-cap structure of mRNAs. Methylates the ribose of the first nucleotide of a m(7)GpppG-capped mRNA and small nuclear RNA (snRNA) to produce m(7)GpppRm (cap1). Displays a preference for cap0 transcripts. Cap1 modification is linked to higher levels of translation. May be involved in the interferon response pathway.
• BioCyc Pathway: MetaCyc:ENSG00000137200-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Beckwith-Wiedemann syndrome	DISH15GR	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Rhabdomyosarcoma	DISNR7MS	Strong	Genetic Variation	[1]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cap-specific mRNA (CMTR1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cap-specific mRNA (CMTR1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cap-specific mRNA (CMTR1).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cap-specific mRNA (CMTR1).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cap-specific mRNA (CMTR1).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cap-specific mRNA (CMTR1).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Cap-specific mRNA (CMTR1).	[9]

4 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 increases the methylation of Cap-specific mRNA (CMTR1).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Cap-specific mRNA (CMTR1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cap-specific mRNA (CMTR1).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Cap-specific mRNA (CMTR1).	[11]

References

• [1] Identification and characterization of MTR1, a novel gene with homology to melastatin (MLSN1) and the trp gene family located in the BWS-WT2 critical region on chromosome 11p15.5 and showing allele-specific expression.Hum Mol Genet. 2000 Jan 22;9(2):203-16. doi: 10.1093/hmg/9.2.203.
• [2] Cytotoxic T lymphocytes from humans with adenocarcinomas stimulated by native MUC1 mucin and a mucin peptide mutated at a glycosylation site.J Immunother. 2000 Jan;23(1):2-10. doi: 10.1097/00002371-200001000-00002.
• [3] 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.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] 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.
• [11] 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.
• [12] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.