Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW7DH2F)

• DOT Name: Elongation factor 1-gamma (EEF1G)
• Synonyms: EF-1-gamma; eEF-1B gamma
• Gene Name: EEF1G
• Related Disease:
  Adenocarcinoma
  Adenoma
  Advanced cancer
  Carcinoma of esophagus
  Colorectal carcinoma
  Glioma
  Lung cancer
  Lung carcinoma
  Pancreatic cancer
  Pancreatic tumour
  Stomach cancer
  Colorectal adenoma
  Familial adenomatous polyposis
• UniProt ID: EF1G_HUMAN
• PDB ID: 1PBU; 5DQS; 5JPO
• Pfam ID: PF00647 ; PF00043 ; PF02798
• Sequence:
  MAAGTLYTYPENWRAFKALIAAQYSGAQVRVLSAPPHFHFGQTNRTPEFLRKFPAGKVPA
  FEGDDGFCVFESNAIAYYVSNEELRGSTPEAAAQVVQWVSFADSDIVPPASTWVFPTLGI
  MHHNKQATENAKEEVRRILGLLDAYLKTRTFLVGERVTLADITVVCTLLWLYKQVLEPSF
  RQAFPNTNRWFLTCINQPQFRAVLGEVKLCEKMAQFDAKKFAETQPKKDTPRKEKGSREE
  KQKPQAERKEEKKAAAPAPEEEMDECEQALAAEPKAKDPFAHLPKSTFVLDEFKRKYSNE
  DTLSVALPYFWEHFDKDGWSLWYSEYRFPEELTQTFMSCNLITGMFQRLDKLRKNAFASV
  ILFGTNNSSSISGVWVFRGQELAFPLSPDWQVDYESYTWRKLDPGSEETQTLVREYFSWE
  GAFQHVGKAFNQGKIFK
• Function: Probably plays a role in anchoring the complex to other cellular components.
• Tissue Specificity: Highly expressed in pancreatic tumor tissue and to a lesser extent in normal kidney, intestine, pancreas, stomach, lung, brain, spleen and liver.
• KEGG Pathway: Legionellosis (hsa05134)
• Reactome Pathway:
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Eukaryotic Translation Elongation (R-HSA-156842)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Adenoma	DIS78ZEV	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Altered Expression	[6]
Lung cancer	DISCM4YA	Strong	Biomarker	[7]
Lung carcinoma	DISTR26C	Strong	Biomarker	[7]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[8]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[1]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[2]
Colorectal adenoma	DISTSVHM	Limited	Altered Expression	[9]
Familial adenomatous polyposis	DISW53RE	Limited	Altered Expression	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Elongation factor 1-gamma (EEF1G).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Elongation factor 1-gamma (EEF1G).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Elongation factor 1-gamma (EEF1G).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Elongation factor 1-gamma (EEF1G).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Elongation factor 1-gamma (EEF1G).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Elongation factor 1-gamma (EEF1G).	[16]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of Elongation factor 1-gamma (EEF1G).	[17]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Elongation factor 1-gamma (EEF1G).	[18]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Elongation factor 1-gamma (EEF1G).	[19]
Etretinate	DM2CZFA	Approved	Etretinate increases the expression of Elongation factor 1-gamma (EEF1G).	[20]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin decreases the expression of Elongation factor 1-gamma (EEF1G).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Elongation factor 1-gamma (EEF1G).	[24]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Elongation factor 1-gamma (EEF1G).	[26]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Elongation factor 1-gamma (EEF1G).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Elongation factor 1-gamma (EEF1G).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Elongation factor 1-gamma (EEF1G).	[22]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Elongation factor 1-gamma (EEF1G).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Elongation factor 1-gamma (EEF1G).	[25]

References

• [1] Expression of an elongation factor 1 gamma-related sequence in adenocarcinomas of the colon.Gastroenterology. 1992 Jul;103(1):98-102. doi: 10.1016/0016-5085(92)91101-9.
• [2] The overexpression of elongation factor 1 gamma mRNA in gastric carcinoma.Cancer. 1995 Mar 15;75(6 Suppl):1446-9. doi: 10.1002/1097-0142(19950315)75:6+<1446::aid-cncr2820751509>3.0.co;2-p.
• [3] Identification of Potential Anticancer Protein Targets in Cytotoxicity Mediated by Tropical Medicinal Fern Extracts.Pharmacogn Mag. 2018 Apr-Jun;14(54):227-230. doi: 10.4103/pm.pm_282_17. Epub 2018 Apr 10.
• [4] Elongation factor 1 gamma mRNA expression in oesophageal carcinoma.Gut. 1996 Jan;38(1):66-70. doi: 10.1136/gut.38.1.66.
• [5] Translational control in the stress adaptive response of cancer cells: a novel role for the heat shock protein TRAP1.Cell Death Dis. 2013 Oct 10;4(10):e851. doi: 10.1038/cddis.2013.379.
• [6] 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.
• [7] 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.
• [8] Expression of elongation factor-1 gamma-related sequence in human pancreatic cancer.Pancreas. 1992;7(2):144-52. doi: 10.1097/00006676-199203000-00003.
• [9] Overexpression of an elongation factor-1 gamma-hybridizing RNA in colorectal adenomas.Mol Carcinog. 1993;7(1):18-20. doi: 10.1002/mc.2940070104.
• [10] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [11] 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.
• [12] Identification of estrogen-induced genes downregulated by AhR agonists in MCF-7 breast cancer cells using suppression subtractive hybridization. Gene. 2001 Jan 10;262(1-2):207-14. doi: 10.1016/s0378-1119(00)00530-8.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [17] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [18] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [19] Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
• [20] Consequences of the natural retinoid/retinoid X receptor ligands action in human breast cancer MDA-MB-231 cell line: Focus on functional proteomics. Toxicol Lett. 2017 Nov 5;281:26-34. doi: 10.1016/j.toxlet.2017.09.001. Epub 2017 Sep 5.
• [21] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [22] 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.
• [23] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [24] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [25] 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.
• [26] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [27] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.