Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW64NPU)

• DOT Name: Elongation factor 1-beta (EEF1B2)
• Synonyms: EF-1-beta
• Gene Name: EEF1B2
• Related Disease:
  Visceral leishmaniasis
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Intellectual disability
  Neurodevelopmental disorder
• UniProt ID: EF1B_HUMAN
• PDB ID: 1B64; 5DQS
• Pfam ID: PF10587 ; PF00736
• Sequence:
  MGFGDLKSPAGLQVLNDYLADKSYIEGYVPSQADVAVFEAVSSPPPADLCHALRWYNHIK
  SYEKEKASLPGVKKALGKYGPADVEDTTGSGATDSKDDDDIDLFGSDDEEESEEAKRLRE
  ERLAQYESKKAKKPALVAKSSILLDVKPWDDETDMAKLEECVRSIQADGLVWGSSKLVPV
  GYGIKKLQIQCVVEDDKVGTDMLEEQITAFEDYVQSMDVAAFNKI
• Function: EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP.
• Reactome Pathway: Eukaryotic Translation Elongation (R-HSA-156842)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Visceral leishmaniasis	DISTKEYK	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[4]
Lung carcinoma	DISTR26C	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Intellectual disability	DISMBNXP	moderate	Genetic Variation	[6]
Neurodevelopmental disorder	DIS372XH	Limited	Biomarker	[7]

5 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 Elongation factor 1-beta (EEF1B2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the phosphorylation of Elongation factor 1-beta (EEF1B2).	[11]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Elongation factor 1-beta (EEF1B2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Elongation factor 1-beta (EEF1B2).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Elongation factor 1-beta (EEF1B2).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Elongation factor 1-beta (EEF1B2).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Elongation factor 1-beta (EEF1B2).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Elongation factor 1-beta (EEF1B2).	[12]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Elongation factor 1-beta (EEF1B2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Elongation factor 1-beta (EEF1B2).	[17]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Elongation factor 1-beta (EEF1B2).	[18]

References

• [1] Recombinant Leishmania eukaryotic elongation factor-1 beta protein: A potential diagnostic antigen to detect tegumentary and visceral leishmaniasis in dogs and humans.Microb Pathog. 2019 Dec;137:103783. doi: 10.1016/j.micpath.2019.103783. Epub 2019 Oct 7.
• [2] Glycolytic cancer associated fibroblasts promote breast cancer tumor growth, without a measurable increase in angiogenesis: evidence for stromal-epithelial metabolic coupling.Cell Cycle. 2010 Jun 15;9(12):2412-22. doi: 10.4161/cc.9.12.11989. Epub 2010 Jun 15.
• [3] Alterations in Eukaryotic Elongation Factor complex proteins (EEF1s) in cancer and their implications in epigenetic regulation.Life Sci. 2019 Dec 1;238:116977. doi: 10.1016/j.lfs.2019.116977. Epub 2019 Oct 19.
• [4] The expression profile and prognostic significance of eukaryotic translation elongation factors in different cancers.PLoS One. 2018 Jan 17;13(1):e0191377. doi: 10.1371/journal.pone.0191377. eCollection 2018.
• [5] Independent overexpression of the subunits of translation elongation factor complex eEF1H in human lung cancer.BMC Cancer. 2014 Dec 3;14:913. doi: 10.1186/1471-2407-14-913.
• [6] New evidence that biallelic loss of function in EEF1B2 gene leads to intellectual disability.Clin Genet. 2020 Apr;97(4):639-643. doi: 10.1111/cge.13688. Epub 2020 Jan 7.
• [7] The role of translation elongation factor eEF1 subunits in neurodevelopmental disorders.Hum Mutat. 2019 Feb;40(2):131-141. doi: 10.1002/humu.23677. Epub 2018 Nov 23.
• [8] 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.
• [9] Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] The G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Nuclear Estrogen Receptor Activity and Stimulates Novel Phosphoproteomic Signatures. Toxicol Sci. 2016 Jun;151(2):434-46. doi: 10.1093/toxsci/kfw057. Epub 2016 Mar 29.
• [12] 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.
• [13] 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.
• [14] Quantitative proteomic analysis of HepG2 cells treated with quercetin suggests IQGAP1 involved in quercetin-induced regulation of cell proliferation and migration. OMICS. 2009 Apr;13(2):93-103. doi: 10.1089/omi.2008.0075.
• [15] 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.
• [16] 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.
• [17] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [18] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.