Details of Drug Off-Target (DOT)

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

• DOT Name: Eukaryotic translation initiation factor 1A, Y-chromosomal (EIF1AY)
• Synonyms: eIF-1A Y isoform; eIF1A Y isoform; Eukaryotic translation initiation factor 4C; eIF-4C
• Gene Name: EIF1AY
• Related Disease:
  Azoospermia
  Immune system disorder
• UniProt ID: IF1AY_HUMAN
• Pfam ID: PF01176
• Sequence:
  MPKNKGKGGKNRRRGKNENESEKRELVFKEDGQEYAQVIKMLGNGRLEALCFDGVKRLCH
  IRGKLRKKVWINTSDIILVGLRDYQDNKADVILKYNADEARSLKAYGELPEHAKINETDT
  FGPGDDDEIQFDDIGDDDEDIDDI
• Function: Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. This protein enhances formation of the cap-proximal complex. Together with EIF1, facilitates scanning, start codon recognition, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. After start codon location, together with EIF5B orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after 80S initiation complex formation, just after GTP hydrolysis by EIF5B, and before release of EIF5B. Its globular part is located in the A site of the 40S ribosomal subunit. Its interaction with EIF5 during scanning contribute to the maintenance of EIF1 within the open 43S PIC. In contrast to yeast orthologs, does not bind EIF1.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Azoospermia	DIS94181	Strong	Altered Expression	[1]
Immune system disorder	DISAEGPH	moderate	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Eukaryotic translation initiation factor 1A, Y-chromosomal (EIF1AY).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Eukaryotic translation initiation factor 1A, Y-chromosomal (EIF1AY).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Eukaryotic translation initiation factor 1A, Y-chromosomal (EIF1AY).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Eukaryotic translation initiation factor 1A, Y-chromosomal (EIF1AY).	[6]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Eukaryotic translation initiation factor 1A, Y-chromosomal (EIF1AY).	[7]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Eukaryotic translation initiation factor 1A, Y-chromosomal (EIF1AY).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Eukaryotic translation initiation factor 1A, Y-chromosomal (EIF1AY).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Eukaryotic translation initiation factor 1A, Y-chromosomal (EIF1AY).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Eukaryotic translation initiation factor 1A, Y-chromosomal (EIF1AY).	[9]

References

• [1] Expression profile of AZF genes in testicular biopsies of azoospermic men.Hum Reprod. 2007 Jan;22(1):151-8. doi: 10.1093/humrep/del341. Epub 2006 Aug 26.
• [2] Gender differences of B cell signature in healthy subjects underlie disparities in incidence and course of SLE related to estrogen.J Immunol Res. 2014;2014:814598. doi: 10.1155/2014/814598. Epub 2014 Feb 13.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] 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.
• [5] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [6] 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.
• [7] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [8] Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.
• [9] 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.
• [10] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.