Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYS7O69)

• DOT Name: Enhancer of mRNA-decapping protein 3 (EDC3)
• Synonyms: LSM16 homolog; YjeF N-terminal domain-containing protein 2; YjeF_N2; hYjeF_N2; YjeF domain-containing protein 1
• Gene Name: EDC3
• Related Disease:
  Neuroblastoma
  Zika virus infection
  Autosomal recessive non-syndromic intellectual disability
  Intellectual disability
  Intellectual disability, autosomal recessive 50
• UniProt ID: EDC3_HUMAN
• PDB ID: 2VC8; 2WAX; 2WAY; 3D3J; 3D3K; 6S8S
• Pfam ID: PF16598 ; PF09532 ; PF12701 ; PF03853
• Sequence:
  MATDWLGSIVSINCGDSLGVYQGRVSAVDQVSQTISLTRPFHNGVKCLVPEVTFRAGDIT
  ELKILEIPGPGDNQHFGDLHQTELGPSGAGCQVGINQNGTGKFVKKPASSSSAPQNIPKR
  TDVKSQDVAVSPQQQQCSKSYVDRHMESLSQSKSFRRRHNSWSSSSRHPNQATPKKSGLK
  NGQMKNKDDECFGDDIEEIPDTDFDFEGNLALFDKAAVFEEIDTYERRSGTRSRGIPNER
  PTRYRHDENILESEPIVYRRIIVPHNVSKEFCTDSGLVVPSISYELHKKLLSVAEKHGLT
  LERRLEMTGVCASQMALTLLGGPNRLNPKNVHQRPTVALLCGPHVKGAQGISCGRHLANH
  DVQVILFLPNFVKMLESITNELSLFSKTQGQQVSSLKDLPTSPVDLVINCLDCPENVFLR
  DQPWYKAAVAWANQNRAPVLSIDPPVHEVEQGIDAKWSLALGLPLPLGEHAGRIYLCDIG
  IPQQVFQEVGINYHSPFGCKFVIPLHSA
• Function: Binds single-stranded RNA. Involved in the process of mRNA degradation and in the positive regulation of mRNA decapping. May play a role in spermiogenesis and oogenesis.
• Tissue Specificity: Expressed in theca and granulosa cells in ovary, and in spermatids of the meiotic division part II and apical membrane of Sertoli cells in testis (at protein level). Also expressed in brain and mammary gland.
• KEGG Pathway: R. degradation (hsa03018)
• Reactome Pathway: mRNA decay by 5' to 3' exoribonuclease (R-HSA-430039)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[1]
Zika virus infection	DISQUCTY	Strong	Biomarker	[2]
Autosomal recessive non-syndromic intellectual disability	DISJWRZZ	Supportive	Autosomal recessive	[3]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[1]
Intellectual disability, autosomal recessive 50	DISLXA7U	Limited	Autosomal recessive	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Enhancer of mRNA-decapping protein 3 (EDC3).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Enhancer of mRNA-decapping protein 3 (EDC3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Enhancer of mRNA-decapping protein 3 (EDC3).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Enhancer of mRNA-decapping protein 3 (EDC3).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Enhancer of mRNA-decapping protein 3 (EDC3).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Enhancer of mRNA-decapping protein 3 (EDC3).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Enhancer of mRNA-decapping protein 3 (EDC3).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Enhancer of mRNA-decapping protein 3 (EDC3).	[10]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Enhancer of mRNA-decapping protein 3 (EDC3).	[13]

3 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 decreases the phosphorylation of Enhancer of mRNA-decapping protein 3 (EDC3).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Enhancer of mRNA-decapping protein 3 (EDC3).	[11]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Enhancer of mRNA-decapping protein 3 (EDC3).	[12]

References

• [1] Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability.BMC Med Genomics. 2018 Apr 23;11(1):41. doi: 10.1186/s12920-018-0358-6.
• [2] Zika virus noncoding sfRNAs sequester multiple host-derived RNA-binding proteins and modulate mRNA decay and splicing during infection.J Biol Chem. 2019 Nov 1;294(44):16282-16296. doi: 10.1074/jbc.RA119.009129. Epub 2019 Sep 13.
• [3] Mutations in DCPS and EDC3 in autosomal recessive intellectual disability indicate a crucial role for mRNA decapping in neurodevelopment. Hum Mol Genet. 2015 Jun 1;24(11):3172-80. doi: 10.1093/hmg/ddv069. Epub 2015 Feb 20.
• [4] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [5] 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.
• [6] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [7] 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.
• [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] Gene expression changes in human prostate carcinoma cells exposed to genotoxic and nongenotoxic aryl hydrocarbon receptor ligands. Toxicol Lett. 2011 Oct 10;206(2):178-88.
• [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] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
• [13] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.