Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4SY4KY)

• DOT Name: Eukaryotic translation initiation factor 5A-2 (EIF5A2)
• Synonyms: eIF-5A-2; eIF-5A2; Eukaryotic initiation factor 5A isoform 2
• Gene Name: EIF5A2
• UniProt ID: IF5A2_HUMAN
• Pfam ID: PF01287 ; PF21485
• Sequence:
  MADEIDFTTGDAGASSTYPMQCSALRKNGFVVLKGRPCKIVEMSTSKTGKHGHAKVHLVG
  IDIFTGKKYEDICPSTHNMDVPNIKRNDYQLICIQDGYLSLLTETGEVREDLKLPEGELG
  KEIEGKYNAGEDVQVSVMCAMSEEYAVAIKPCK
• Function: Translation factor that promotes translation elongation and termination, particularly upon ribosome stalling at specific amino acid sequence contexts. Binds between the exit (E) and peptidyl (P) site of the ribosome and promotes rescue of stalled ribosome: specifically required for efficient translation of polyproline-containing peptides as well as other motifs that stall the ribosome. Acts as a ribosome quality control (RQC) cofactor by joining the RQC complex to facilitate peptidyl transfer during CAT tailing step. Also involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity.
• Tissue Specificity: Expressed in ovarian and colorectal cancer cell lines (at protein level). Highly expressed in testis. Overexpressed in some cancer cells.
• Reactome Pathway: Hypusine synthesis from eIF5A-lysine (R-HSA-204626)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[15]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[16]
Forskolin	DM6ITNG	Investigative	Forskolin decreases the expression of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Eukaryotic translation initiation factor 5A-2 (EIF5A2).	[11]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] GLI inhibitors overcome Erlotinib resistance in human pancreatic cancer cells by modulating E-cadherin. J Chemother. 2019 May;31(3):141-149. doi: 10.1080/1120009X.2019.1584422. Epub 2019 Apr 14.
• [9] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [10] 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.
• [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] 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.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [16] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.