Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZTT22W)

DOT Name Eukaryotic translation initiation factor 5B (EIF5B)
Synonyms eIF-5B; EC 3.6.5.3; Translation initiation factor IF-2
Gene Name EIF5B
Related Disease
Adult glioblastoma ( )
Adenocarcinoma ( )
Brain neoplasm ( )
Breast cancer ( )
Hepatocellular carcinoma ( )
Major depressive disorder ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Hepatitis C virus infection ( )
UniProt ID
IF2P_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7TQL
EC Number
3.6.5.3
Pfam ID
PF00009 ; PF14578 ; PF11987
Sequence
MGKKQKNKSEDSTKDDIDLDALAAEIEGAGAAKEQEPQKSKGKKKKEKKKQDFDEDDILK
ELEELSLEAQGIKADRETVAVKPTENNEEEFTSKDKKKKGQKGKKQSFDDNDSEELEDKD
SKSKKTAKPKVEMYSGSDDDDDFNKLPKKAKGKAQKSNKKWDGSEEDEDNSKKIKERSRI
NSSGESGDESDEFLQSRKGQKKNQKNKPGPNIESGNEDDDASFKIKTVAQKKAEKKERER
KKRDEEKAKLRKLKEKEELETGKKDQSKQKESQRKFEEETVKSKVTVDTGVIPASEEKAE
TPTAAEDDNEGDKKKKDKKKKKGEKEEKEKEKKKGPSKATVKAMQEALAKLKEEEERQKR
EEEERIKRLEELEAKRKEEERLEQEKRERKKQKEKERKERLKKEGKLLTKSQREARARAE
ATLKLLQAQGVEVPSKDSLPKKRPIYEDKKRKKIPQQLESKEVSESMELCAAVEVMEQGV
PEKEETPPPVEPEEEEDTEDAGLDDWEAMASDEETEKVEGNKVHIEVKENPEEEEEEEEE
EEEDEESEEEEEEEGESEGSEGDEEDEKVSDEKDSGKTLDKKPSKEMSSDSEYDSDDDRT
KEERAYDKAKRRIEKRRLEHSKNVNTEKLRAPIICVLGHVDTGKTKILDKLRHTHVQDGE
AGGITQQIGATNVPLEAINEQTKMIKNFDRENVRIPGMLIIDTPGHESFSNLRNRGSSLC
DIAILVVDIMHGLEPQTIESINLLKSKKCPFIVALNKIDRLYDWKKSPDSDVAATLKKQK
KNTKDEFEERAKAIIVEFAQQGLNAALFYENKDPRTFVSLVPTSAHTGDGMGSLIYLLVE
LTQTMLSKRLAHCEELRAQVMEVKALPGMGTTIDVILINGRLKEGDTIIVPGVEGPIVTQ
IRGLLLPPPMKELRVKNQYEKHKEVEAAQGVKILGKDLEKTLAGLPLLVAYKEDEIPVLK
DELIHELKQTLNAIKLEEKGVYVQASTLGSLEALLEFLKTSEVPYAGINIGPVHKKDVMK
ASVMLEHDPQYAVILAFDVRIERDAQEMADSLGVRIFSAEIIYHLFDAFTKYRQDYKKQK
QEEFKHIAVFPCKIKILPQYIFNSRDPIVMGVTVEAGQVKQGTPMCVPSKNFVDIGIVTS
IEINHKQVDVAKKGQEVCVKIEPIPGESPKMFGRHFEATDILVSKISRQSIDALKDWFRD
EMQKSDWQLIVELKKVFEII
Function
Plays a role in translation initiation. Ribosome-dependent GTPase that promotes the joining of the 60S ribosomal subunit to the pre-initiation complex to form the 80S initiation complex with the initiator methionine-tRNA in the P-site base paired to the start codon. Together with eIF1A (EIF1AX), actively orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after formation of the 80S initiation complex. Its GTPase activity is not essential for ribosomal subunits joining, but GTP hydrolysis is needed for eIF1A (EIF1AX) ejection quickly followed by EIF5B release to form elongation-competent ribosomes. In contrast to its procaryotic homolog, does not promote recruitment of Met-rRNA to the small ribosomal subunit.
Reactome Pathway
GTP hydrolysis and joining of the 60S ribosomal subunit (R-HSA-72706 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Definitive Biomarker [1]
Adenocarcinoma DIS3IHTY Strong Genetic Variation [2]
Brain neoplasm DISY3EKS Strong Biomarker [3]
Breast cancer DIS7DPX1 Strong Genetic Variation [4]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [5]
Major depressive disorder DIS4CL3X Strong Genetic Variation [6]
Neoplasm DISZKGEW Strong Biomarker [3]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [7]
Hepatitis C virus infection DISQ0M8R Limited Biomarker [8]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Mitomycin DMH0ZJE Approved Eukaryotic translation initiation factor 5B (EIF5B) affects the response to substance of Mitomycin. [23]
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12 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 5B (EIF5B). [9]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Eukaryotic translation initiation factor 5B (EIF5B). [10]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Eukaryotic translation initiation factor 5B (EIF5B). [11]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Eukaryotic translation initiation factor 5B (EIF5B). [12]
Marinol DM70IK5 Approved Marinol increases the expression of Eukaryotic translation initiation factor 5B (EIF5B). [13]
Piroxicam DMTK234 Approved Piroxicam decreases the expression of Eukaryotic translation initiation factor 5B (EIF5B). [14]
Clozapine DMFC71L Approved Clozapine increases the expression of Eukaryotic translation initiation factor 5B (EIF5B). [15]
Benzatropine DMF7EXL Approved Benzatropine increases the expression of Eukaryotic translation initiation factor 5B (EIF5B). [15]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Eukaryotic translation initiation factor 5B (EIF5B). [16]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Eukaryotic translation initiation factor 5B (EIF5B). [18]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Eukaryotic translation initiation factor 5B (EIF5B). [20]
Glyphosate DM0AFY7 Investigative Glyphosate increases the expression of Eukaryotic translation initiation factor 5B (EIF5B). [21]
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⏷ Show the Full List of 12 Drug(s)
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Eukaryotic translation initiation factor 5B (EIF5B). [17]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Eukaryotic translation initiation factor 5B (EIF5B). [19]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Eukaryotic translation initiation factor 5B (EIF5B). [19]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid increases the phosphorylation of Eukaryotic translation initiation factor 5B (EIF5B). [22]
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References

1 Eukaryotic initiation factor 5B (eIF5B) provides a critical cell survival switch to glioblastoma cells via regulation of apoptosis.Cell Death Dis. 2019 Jan 22;10(2):57. doi: 10.1038/s41419-018-1283-5.
2 A pan-cancer genome-wide analysis reveals tumour dependencies by induction of nonsense-mediated decay.Nat Commun. 2017 Jun 26;8:15943. doi: 10.1038/ncomms15943.
3 Eukaryotic initiation factor 5B (eIF5B) regulates temozolomide-mediated apoptosis in brain tumour stem cells (BTSCs).Biochem Cell Biol. 2020 Dec;98(6):647-652. doi: 10.1139/bcb-2019-0329. Epub 2019 Oct 31.
4 Inconsistent Results With Different Secondary Reflex Assays for Resolving HER2 Status.Am J Clin Pathol. 2016 Nov 1;146(5):618-626. doi: 10.1093/ajcp/aqw177.
5 eIF5B increases ASAP1 expression to promote HCC proliferation and invasion.Oncotarget. 2016 Sep 20;7(38):62327-62339. doi: 10.18632/oncotarget.11469.
6 A mega-analysis of genome-wide association studies for major depressive disorder.Mol Psychiatry. 2013 Apr;18(4):497-511. doi: 10.1038/mp.2012.21. Epub 2012 Apr 3.
7 Ileal interposition coupled with duodenal diverted sleeve gastrectomy versus standard medical treatment in type 2 diabetes mellitus obese patients: long-term results of a case-control study.Surg Endosc. 2019 May;33(5):1553-1563. doi: 10.1007/s00464-018-6443-2. Epub 2018 Sep 17.
8 Four translation initiation pathways employed by the leaderless mRNA in eukaryotes.Sci Rep. 2016 Nov 28;6:37905. doi: 10.1038/srep37905.
9 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
10 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
11 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.
12 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.
13 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
14 Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
15 Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
16 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
17 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
18 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
19 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.
20 Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
21 Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways. Environ Int. 2020 Feb;135:105414. doi: 10.1016/j.envint.2019.105414. Epub 2019 Dec 23.
22 Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
23 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.