Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLA4ONW)

• DOT Name: Eukaryotic translation initiation factor 5A-1-like (EIF5AL1)
• Synonyms: eIF-5A-1-like; eIF-5A1-like; Eukaryotic initiation factor 5A isoform 1-like
• Gene Name: EIF5AL1
• Related Disease:
  Malaria
  Colorectal carcinoma
  Epithelial ovarian cancer
  Lung adenocarcinoma
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Qualitative or quantitative defects of dysferlin
• UniProt ID: IF5AL_HUMAN
• Pfam ID: PF01287 ; PF21485
• Sequence:
  MADDLDFETGDAGASATFPMQCSALRKNGFVVLKGWPCKIVEMSASKTGKHGHAKVHLVG
  IDIFTGKKYEDICPSTHNMDVPNIKRNDFQLIGIQDGYLSLLQDSGEVPEDLRLPEGDLG
  KEIEQKYDCGEEILITVLSAMTEEAAVAIKAMAK
• 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.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Definitive	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[3]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Qualitative or quantitative defects of dysferlin	DIS59VEJ	Strong	Biomarker	[5]

2 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 5A-1-like (EIF5AL1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Eukaryotic translation initiation factor 5A-1-like (EIF5AL1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Eukaryotic translation initiation factor 5A-1-like (EIF5AL1).	[7]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Eukaryotic translation initiation factor 5A-1-like (EIF5AL1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Eukaryotic translation initiation factor 5A-1-like (EIF5AL1).	[10]

References

• [1] Deoxyhypusine hydroxylase from Plasmodium vivax, the neglected human malaria parasite: molecular cloning, expression and specific inhibition by the 5-LOX inhibitor zileuton.PLoS One. 2013;8(3):e58318. doi: 10.1371/journal.pone.0058318. Epub 2013 Mar 7.
• [2] Integrative analysis of significant RNA-binding proteins in colorectal cancer metastasis.J Cell Biochem. 2018 Dec;119(12):9730-9741. doi: 10.1002/jcb.27290. Epub 2018 Aug 21.
• [3] Isolation of a novel candidate oncogene within a frequently amplified region at 3q26 in ovarian cancer.Cancer Res. 2001 May 1;61(9):3806-9.
• [4] Proteomic analysis of eIF-5A in lung adenocarcinomas.Proteomics. 2003 Apr;3(4):496-504. doi: 10.1002/pmic.200390063.
• [5] Proteomic analysis of the skeletal muscles from dysferlinopathy patients.J Clin Neurosci. 2020 Jan;71:186-190. doi: 10.1016/j.jocn.2019.08.068. Epub 2019 Aug 19.
• [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] 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.
• [8] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [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] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.