Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX7PHCI)

• DOT Name: mRNA-decapping enzyme 1B (DCP1B)
• Synonyms: EC 3.6.1.62
• Gene Name: DCP1B
• Related Disease:
  Respiratory syncytial virus infection
  Age-related macular degeneration
  Depression
  High blood pressure
  Myocardial infarction
  Obesity
  Vascular disease
• UniProt ID: DCP1B_HUMAN
• EC Number: 3.6.1.62
• Pfam ID: PF06058 ; PF16741
• Sequence:
  MAAVAAGGLVGKGRDISLAALQRHDPYINRIVDVASQVALYTFGHRANEWEKTDVEGTLF
  VYTRSASPKHGFTIMNRLSMENRTEPITKDLDFQLQDPFLLYRNARLSIYGIWFYDKEEC
  QRIAELMKNLTQYEQLKAHQGTGAGISPVILNSGEGKEVDILRMLIKAKDEYTKCKTCSE
  PKKITSSSAIYDNPNLIKPIPVKPSENQQQRIPQPNQTLDPEPQHLSLTALFGKQDKATC
  QETVEPPQTLHQQQQQQQQQQEKLPIRQGVVRSLSYEEPRRHSPPIEKQLCPAIQKLMVR
  SADLHPLSELPENRPCENGSTHSAGEFFTGPVQPGSPHNIGTSRGVQNASRTQNLFEKLQ
  STPGAANKCDPSTPAPASSAALNRSRAPTSVTPVAPGKGLAQPPQAYFNGSLPPQTVGHQ
  AHGREQSTLPRQTLPISGSQTGSSGVISPQELLKKLQIVQQEQQLHASNRPALAAKFPVL
  AQSSGTGKPLESWINKTPNTEQQTPLFQVISPQRIPATAAPSLLMSPMVFAQPTSVPPKE
  RESGLLPVGGQEPPAAATSLLLPIQSPEPSVITSSPLTKLQLQEALLYLIQNDDNFLNII
  YEAYLFSMTQAAMKKTM
• Function: May play a role in the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay. May remove the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP.
• KEGG Pathway: R. degradation (hsa03018)
• Reactome Pathway: mRNA decay by 5' to 3' exoribonuclease (R-HSA-430039)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Respiratory syncytial virus infection	DIS7FWHY	Definitive	Biomarker	[1]
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[2]
Depression	DIS3XJ69	Strong	Biomarker	[3]
High blood pressure	DISY2OHH	Strong	Biomarker	[4]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[4]
Obesity	DIS47Y1K	Strong	Genetic Variation	[4]
Vascular disease	DISVS67S	Strong	Genetic Variation	[3]

9 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 mRNA-decapping enzyme 1B (DCP1B).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of mRNA-decapping enzyme 1B (DCP1B).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of mRNA-decapping enzyme 1B (DCP1B).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of mRNA-decapping enzyme 1B (DCP1B).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of mRNA-decapping enzyme 1B (DCP1B).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of mRNA-decapping enzyme 1B (DCP1B).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of mRNA-decapping enzyme 1B (DCP1B).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of mRNA-decapping enzyme 1B (DCP1B).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of mRNA-decapping enzyme 1B (DCP1B).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of mRNA-decapping enzyme 1B (DCP1B).	[13]

References

• [1] Decapping protein 1 phosphorylation modulates IL-8 expression during respiratory syncytial virus infection.Virology. 2015 Jul;481:199-209. doi: 10.1016/j.virol.2015.02.043. Epub 2015 Mar 19.
• [2] Functional candidate genes in age-related macular degeneration: significant association with VEGF, VLDLR, and LRP6.Invest Ophthalmol Vis Sci. 2006 Jan;47(1):329-35. doi: 10.1167/iovs.05-0116.
• [3] Genes related to vascular disease (APOE, VLDL-R, DCP-1) and other vascular factors in late-life depression.Am J Geriatr Psychiatry. 2004 Mar-Apr;12(2):202-10.
• [4] Chromosome 17q23: a locus for cardiovascular disease.Clin Exp Pharmacol Physiol. 1993 May;20(5):279-82. doi: 10.1111/j.1440-1681.1993.tb01683.x.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [12] 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.
• [13] 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.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.