Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE109AY)

• DOT Name: Eukaryotic translation initiation factor 2D (EIF2D)
• Synonyms: eIF2d; Hepatocellular carcinoma-associated antigen 56; Ligatin
• Gene Name: EIF2D
• Related Disease:
  Hepatitis C virus infection
  Schizophrenia
• UniProt ID: EIF2D_HUMAN
• PDB ID: 5OA3; 5OA9; 5W2F
• Pfam ID: PF17832 ; PF01253
• Sequence:
  MFAKAFRVKSNTAIKGSDRRKLRADVTTAFPTLGTDQVSELVPGKEELNIVKLYAHKGDA
  VTVYVSGGNPILFELEKNLYPTVYTLWSYPDLLPTFTTWPLVLEKLVGGADLMLPGLVMP
  PAGLPQVQKGDLCAISLVGNRAPVAIGVAAMSTAEMLTSGLKGRGFSVLHTYQDHLWRSG
  NKSSPPSIAPLALDSADLSEEKGSVQMDSTLQGDMRHMTLEGEEENGEVHQAREDKSLSE
  APEDTSTRGLNQDSTDSKTLQEQMDELLQQCFLHALKCRVKKADLPLLTSTFLGSHMFSC
  CPEGRQLDIKKSSYKKLSKFLQQMQQEQIIQVKELSKGVESIVAVDWKHPRITSFVIPEP
  SPTSQTIQEGSREQPYHPPDIKPLYCVPASMTLLFQESGHKKGSFLEGSEVRTIVINYAK
  KNDLVDADNKNLVRLDPILCDCILEKNEQHTVMKLPWDSLLTRCLEKLQPAYQVTLPGQE
  PIVKKGRICPIDITLAQRASNKKVTVVRNLEAYGLDPYSVAAILQQRCQASTTVNPAPGA
  KDSLQVQIQGNQVHHLGWLLLEEYQLPRKHIQGLEKALKPGKKK
• Function: Translation initiation factor that is able to deliver tRNA to the P-site of the eukaryotic ribosome in a GTP-independent manner. The binding of Met-tRNA(I) occurs after the AUG codon finds its position in the P-site of 40S ribosomes, the situation that takes place during initiation complex formation on some specific RNAs. Its activity in tRNA binding with 40S subunits does not require the presence of the aminoacyl moiety. Possesses the unique ability to deliver non-Met (elongator) tRNAs into the P-site of the 40S subunit. In addition to its role in initiation, can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[1]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Eukaryotic translation initiation factor 2D (EIF2D).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Eukaryotic translation initiation factor 2D (EIF2D).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Eukaryotic translation initiation factor 2D (EIF2D).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Eukaryotic translation initiation factor 2D (EIF2D).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Eukaryotic translation initiation factor 2D (EIF2D).	[7]

References

• [1] The Initiation Factors eIF2, eIF2A, eIF2D, eIF4A, and eIF4G Are Not Involved in Translation Driven by Hepatitis C Virus IRES in Human Cells.Front Microbiol. 2018 Feb 13;9:207. doi: 10.3389/fmicb.2018.00207. eCollection 2018.
• [2] Time dependent expression of the blood biomarkers EIF2D and TOX in patients with schizophrenia.Brain Behav Immun. 2019 Aug;80:909-915. doi: 10.1016/j.bbi.2019.05.015. Epub 2019 May 9.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [7] 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.