Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5L1SRY)

• DOT Name: Eukaryotic translation initiation factor 3 subunit G (EIF3G)
• Synonyms: eIF3g; Eukaryotic translation initiation factor 3 RNA-binding subunit; eIF-3 RNA-binding subunit; Eukaryotic translation initiation factor 3 subunit 4; eIF-3-delta; eIF3 p42; eIF3 p44
• Gene Name: EIF3G
• Related Disease:
  Breast cancer
  Breast carcinoma
  Narcolepsy 1
  Neoplasm
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Narcolepsy
• UniProt ID: EIF3G_HUMAN
• PDB ID: 2CQ0; 2MJC; 5K0Y; 6YBS; 6ZMW; 7QP6; 7QP7; 8PPL
• Pfam ID: PF12353 ; PF00076
• Sequence:
  MPTGDFDSKPSWADQVEEEGEDDKCVTSELLKGIPLATGDTSPEPELLPGAPLPPPKEVI
  NGNIKTVTEYKIDEDGKKFKIVRTFRIETRKASKAVARRKNWKKFGNSEFDPPGPNVATT
  TVSDDVSMTFITSKEDLNCQEEEDPMNKLKGQKIVSCRICKGDHWTTRCPYKDTLGPMQK
  ELAEQLGLSTGEKEKLPGELEPVQATQNKTGKYVPPSLRDGASRRGESMQPNRRADDNAT
  IRVTNLSEDTRETDLQELFRPFGSISRIYLAKDKTTGQSKGFAFISFHRREDAARAIAGV
  SGFGYDHLILNVEWAKPSTN
• Function: RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression. This subunit can bind 18S rRNA; (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2.
• Reactome Pathway:
  Translation initiation complex formation (R-HSA-72649)
  Formation of a pool of free 40S subunits (R-HSA-72689)
  Formation of the ternary complex, and subsequently, the 43S complex (R-HSA-72695)
  Ribosomal scanning and start codon recognition (R-HSA-72702)
  GTP hydrolysis and joining of the 60S ribosomal subunit (R-HSA-72706)
  L13a-mediated translational silencing of Ceruloplasmin expression (R-HSA-156827)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Narcolepsy 1	DISTYYJ6	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Colon cancer	DISVC52G	Limited	Biomarker	[4]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[4]
Narcolepsy	DISLCNLI	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Eukaryotic translation initiation factor 3 subunit G (EIF3G).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Eukaryotic translation initiation factor 3 subunit G (EIF3G).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Eukaryotic translation initiation factor 3 subunit G (EIF3G).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Eukaryotic translation initiation factor 3 subunit G (EIF3G).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Eukaryotic translation initiation factor 3 subunit G (EIF3G).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Eukaryotic translation initiation factor 3 subunit G (EIF3G).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Eukaryotic translation initiation factor 3 subunit G (EIF3G).	[13]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Eukaryotic translation initiation factor 3 subunit G (EIF3G).	[14]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Eukaryotic translation initiation factor 3 subunit G (EIF3G).	[10]

References

• [1] Nuclear distribution of eIF3g and its interacting nuclear proteins in breast cancer cells.Mol Med Rep. 2016 Apr;13(4):2973-80. doi: 10.3892/mmr.2016.4935. Epub 2016 Feb 23.
• [2] EIF3G is associated with narcolepsy across ethnicities.Eur J Hum Genet. 2015 Nov;23(11):1573-80. doi: 10.1038/ejhg.2015.4. Epub 2015 Feb 11.
• [3] Eukaryotic translation initiation factor 3 subunit G (EIF3G) resensitized HCT116/5-Fu to 5-fluorouracil (5-Fu) via inhibition of MRP and MDR1.Onco Targets Ther. 2018 Aug 31;11:5315-5324. doi: 10.2147/OTT.S170854. eCollection 2018.
• [4] Eukaryotic translation initiation factor 3 subunit G promotes human colorectal cancer.Am J Transl Res. 2019 Feb 15;11(2):612-623. eCollection 2019.
• [5] Rare missense mutations in P2RY11 in narcolepsy with cataplexy.Brain. 2017 Jun 1;140(6):1657-1668. doi: 10.1093/brain/awx093.
• [6] 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.
• [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] 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.
• [9] Proteomic and functional analyses reveal a dual molecular mechanism underlying arsenic-induced apoptosis in human multiple myeloma cells. J Proteome Res. 2009 Jun;8(6):3006-19.
• [10] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [11] 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.
• [12] 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.
• [13] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [14] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.