Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT82FBWS)

• DOT Name: Cap-specific mRNA (CMTR2)
• Synonyms: nucleoside-2'-O-)-methyltransferase 2 (EC 2.1.1.296; Cap methyltransferase 2; Cap2 2'O-ribose methyltransferase 2; HMTr2; MTr2; FtsJ methyltransferase domain-containing protein 1; Protein adrift homolog
• Gene Name: CMTR2
• Related Disease:
  Lung cancer
  Lung carcinoma
  Breast cancer
  Breast carcinoma
  Classic Hodgkin lymphoma
  Hepatocellular carcinoma
  Huntington disease
  Polycystic ovarian syndrome
  Lung adenocarcinoma
• UniProt ID: CMTR2_HUMAN
• EC Number: 2.1.1.296
• Pfam ID: PF01728
• Sequence:
  MSKCRKTPVQQLASPASFSPDILADIFELFAKNFSYGKPLNNEWQLPDPSEIFTCDHTEL
  NAFLDLKNSLNEVKNLLSDKKLDEWHEHTAFTNKAGKIISHVRKSVNAELCTQAWCKFHE
  ILCSFPLIPQEAFQNGKLNSLHLCEAPGAFIASLNHYLKSHRFPCHWSWVANTLNPYHEA
  NDDLMMIMDDRLIANTLHWWYFGPDNTGDIMTLKFLTGLQNFISSMATVHLVTADGSFDC
  QGNPGEQEALVSSLHYCEVVTALTTLGNGGSFVLKMFTMFEHCSINLMYLLNCCFDQVHV
  FKPATSKAGNSEVYVVCLHYKGREAIHPLLSKMTLNFGTEMKRKALFPHHVIPDSFLKRH
  EECCVFFHKYQLETISENIRLFECMGKAEQEKLNNLRDCAIQYFMQKFQLKHLSRNNWLV
  KKSSIGCSTNTKWFGQRNKYFKTYNERKMLEALSWKDKVAKGYFNSWAEEHGVYHPGQSS
  ILEGTASNLECHLWHILEGKKLPKVKCSPFCNGEILKTLNEAIEKSLGGAFNLDSKFRPK
  QQYSCSCHVFSEELIFSELCSLTECLQDEQVVVPSNQIKCLLVGFSTLRNIKMHIPLEVR
  LLESAELTTFSCSLLHDGDPTYQRLFLDCLLHSLRELHTGDVMILPVLSCFTRFMAGLIF
  VLHSCFRFITFVCPTSSDPLRTCAVLLCVGYQDLPNPVFRYLQSVNELLSTLLNSDSPQQ
  VLQFVPMEVLLKGALLDFLWDLNAAIAKRHLHFIIQREREEIINSLQLQN
• Function: S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap2 2'-O-ribose methylation to the 5'-cap structure of mRNAs. Methylates the ribose of the second nucleotide of a m(7)GpppG-capped mRNA and small nuclear RNA (snRNA) (cap0) to produce m(7)GpppRmpNm (cap2). Recognizes a guanosine cap on RNA independently of its N(7) methylation status. Display cap2 methylation on both cap0 and cap1. Displays a preference for cap1 RNAs.
• BioCyc Pathway: MetaCyc:ENSG00000180917-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Genetic Variation	[1]
Lung carcinoma	DISTR26C	Definitive	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[4]
Huntington disease	DISQPLA4	Strong	Biomarker	[3]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[5]
Lung adenocarcinoma	DISD51WR	Disputed	Biomarker	[6]

2 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 Cap-specific mRNA (CMTR2).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cap-specific mRNA (CMTR2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cap-specific mRNA (CMTR2).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cap-specific mRNA (CMTR2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cap-specific mRNA (CMTR2).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cap-specific mRNA (CMTR2).	[12]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Cap-specific mRNA (CMTR2).	[10]

References

• [1] Comorbidity Assessment in the National Cancer Database for Patients With Surgically Resected Breast, Colorectal, or Lung Cancer (AFT-01, -02, -03).J Oncol Pract. 2018 Oct;14(10):e631-e643. doi: 10.1200/JOP.18.00175. Epub 2018 Sep 12.
• [2] Long-term Follow-up of Autologous Fat Transfer vs Conventional Breast Reconstruction and Association With Cancer Relapse in Patients With Breast Cancer.JAMA Surg. 2019 Jan 1;154(1):56-63. doi: 10.1001/jamasurg.2018.3744.
• [3] Factors influencing survival time of hemodialysis patients; time to event analysis using parametric models: a cohort study.BMC Nephrol. 2019 Jun 11;20(1):215. doi: 10.1186/s12882-019-1382-2.
• [4] Genomewide association study for C-reactive protein in Indians replicates known associations of common variants.J Genet. 2019 Mar;98:20.
• [5] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [6] Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas.Nat Genet. 2016 Jun;48(6):607-16. doi: 10.1038/ng.3564. Epub 2016 May 9.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] 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.
• [12] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.