Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI0WG98)

DOT Name Eukaryotic translation initiation factor 3 subunit E (EIF3E)
Synonyms eIF3e; Eukaryotic translation initiation factor 3 subunit 6; Viral integration site protein INT-6 homolog; eIF-3 p48
Gene Name EIF3E
Related Disease
Adult glioblastoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Bladder cancer ( )
Breast carcinoma ( )
Carcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colonic neoplasm ( )
Colorectal carcinoma ( )
Eclampsia ( )
Endometriosis ( )
Esophageal squamous cell carcinoma ( )
Intermittent claudication ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Neoplasm ( )
Precancerous condition ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Vascular disease ( )
Alopecia ( )
Androgenetic alopecia ( )
Baldness, male pattern ( )
Breast cancer ( )
Breast neoplasm ( )
Non-small-cell lung cancer ( )
UniProt ID
EIF3E_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3J8B; 3J8C; 6FEC; 6YBD; 6ZMW; 6ZON; 6ZP4; 6ZVJ; 7A09; 7QP6; 7QP7; 8PPL
Pfam ID
PF09440 ; PF21357 ; PF01399
Sequence
MAEYDLTTRIAHFLDRHLVFPLLEFLSVKEIYNEKELLQGKLDLLSDTNMVDFAMDVYKN
LYSDDIPHALREKRTTVVAQLKQLQAETEPIVKMFEDPETTRQMQSTRDGRMLFDYLADK
HGFRQEYLDTLYRYAKFQYECGNYSGAAEYLYFFRVLVPATDRNALSSLWGKLASEILMQ
NWDAAMEDLTRLKETIDNNSVSSPLQSLQQRTWLIHWSLFVFFNHPKGRDNIIDLFLYQP
QYLNAIQTMCPHILRYLTTAVITNKDVRKRRQVLKDLVKVIQQESYTYKDPITEFVECLY
VNFDFDGAQKKLRECESVLVNDFFLVACLEDFIENARLFIFETFCRIHQCISINMLADKL
NMTPEEAERWIVNLIRNARLDAKIDSKLGHVVMGNNAVSPYQQVIEKTKSLSFRSQMLAM
NIEKKLNQNSRSEAPNWATQDSGFY
Function
Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression. Required for nonsense-mediated mRNA decay (NMD); may act in conjunction with UPF2 to divert mRNAs from translation to the NMD pathway. May interact with MCM7 and EPAS1 and regulate the proteasome-mediated degradation of these proteins.
Tissue Specificity Ubiquitously expressed. Expressed at highest levels in appendix, lymph, pancreas, skeletal muscle, spleen and thymus.
KEGG Pathway
Hepatitis C (hsa05160 )
Reactome Pathway
Translation initiation complex formation (R-HSA-72649 )
Formation of a pool of free 40S subunits (R-HSA-72689 )
Formation of the ternary complex, and subsequently, the 43S complex (R-HSA-72695 )
Ribosomal scanning and start codon recognition (R-HSA-72702 )
GTP hydrolysis and joining of the 60S ribosomal subunit (R-HSA-72706 )
L13a-mediated translational silencing of Ceruloplasmin expression (R-HSA-156827 )

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Strong Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Alzheimer disease DISF8S70 Strong Genetic Variation [3]
Bladder cancer DISUHNM0 Strong Altered Expression [4]
Breast carcinoma DIS2UE88 Strong Biomarker [5]
Carcinoma DISH9F1N Strong Altered Expression [6]
Colon cancer DISVC52G Strong Altered Expression [7]
Colon carcinoma DISJYKUO Strong Altered Expression [7]
Colonic neoplasm DISSZ04P Strong Altered Expression [7]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [8]
Eclampsia DISWPO8U Strong Biomarker [9]
Endometriosis DISX1AG8 Strong Biomarker [10]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [11]
Intermittent claudication DISGY3B0 Strong Therapeutic [12]
Lung adenocarcinoma DISD51WR Strong Biomarker [13]
Lung cancer DISCM4YA Strong Altered Expression [14]
Lung carcinoma DISTR26C Strong Altered Expression [14]
Lung neoplasm DISVARNB Strong Altered Expression [15]
Neoplasm DISZKGEW Strong Biomarker [2]
Precancerous condition DISV06FL Strong Altered Expression [16]
Urinary bladder cancer DISDV4T7 Strong Altered Expression [4]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [4]
Vascular disease DISVS67S Strong Biomarker [2]
Alopecia DIS37HU4 Limited Genetic Variation [17]
Androgenetic alopecia DISSJR1P Limited Genetic Variation [18]
Baldness, male pattern DIS9C9RO Limited Genetic Variation [18]
Breast cancer DIS7DPX1 Limited Biomarker [5]
Breast neoplasm DISNGJLM Limited Biomarker [19]
Non-small-cell lung cancer DIS5Y6R9 Limited Altered Expression [14]
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⏷ Show the Full List of 29 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 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 3 subunit E (EIF3E). [20]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Eukaryotic translation initiation factor 3 subunit E (EIF3E). [21]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Eukaryotic translation initiation factor 3 subunit E (EIF3E). [22]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Eukaryotic translation initiation factor 3 subunit E (EIF3E). [23]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Eukaryotic translation initiation factor 3 subunit E (EIF3E). [24]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Eukaryotic translation initiation factor 3 subunit E (EIF3E). [25]
PMID28870136-Compound-48 DMPIM9L Patented PMID28870136-Compound-48 decreases the expression of Eukaryotic translation initiation factor 3 subunit E (EIF3E). [26]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Eukaryotic translation initiation factor 3 subunit E (EIF3E). [27]
chloropicrin DMSGBQA Investigative chloropicrin affects the expression of Eukaryotic translation initiation factor 3 subunit E (EIF3E). [28]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate decreases the expression of Eukaryotic translation initiation factor 3 subunit E (EIF3E). [29]
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⏷ Show the Full List of 10 Drug(s)

References

1 Int6/eIF3e is essential for proliferation and survival of human glioblastoma cells.Int J Mol Sci. 2014 Jan 29;15(2):2172-90. doi: 10.3390/ijms15022172.
2 The Bad, the Good and eIF3e/INT6.Front Biosci (Landmark Ed). 2017 Jan 1;22(1):1-20. doi: 10.2741/4469.
3 Genome-wide association of familial late-onset Alzheimer's disease replicates BIN1 and CLU and nominates CUGBP2 in interaction with APOE.PLoS Genet. 2011 Feb;7(2):e1001308. doi: 10.1371/journal.pgen.1001308. Epub 2011 Feb 17.
4 Common and differentially expressed long noncoding RNAs for the characterization of high and low grade bladder cancer.Gene. 2016 Oct 30;592(1):78-85. doi: 10.1016/j.gene.2016.07.042. Epub 2016 Jul 20.
5 INT6/EIF3E Controls the RNF8-Dependent Ubiquitylation Pathway and Facilitates DNA Double-Strand Break Repair in Human Cells.Cancer Res. 2016 Oct 15;76(20):6054-6065. doi: 10.1158/0008-5472.CAN-16-0723. Epub 2016 Aug 22.
6 Reduced expression of INT-6/eIF3-p48 in human tumors.Int J Oncol. 2001 Jan;18(1):175-9. doi: 10.3892/ijo.18.1.175.
7 Overexpression of eIF3e is correlated with colon tumor development and poor prognosis.Int J Clin Exp Pathol. 2014 Sep 15;7(10):6462-74. eCollection 2014.
8 EIF3E-RSPO2 and PIEZO1-RSPO2 fusions in colorectal traditional serrated adenoma.Histopathology. 2019 Aug;75(2):266-273. doi: 10.1111/his.13867. Epub 2019 Jun 20.
9 Int6/eIF3e Silencing Promotes Placenta Angiogenesis in a Rat Model of Pre-eclampsia.Sci Rep. 2018 Jun 12;8(1):8944. doi: 10.1038/s41598-018-27296-2.
10 Reduced Expression of Eukaryotic Translation Initiation Factor 3 Subunit e and Its Possible Involvement in the Epithelial-Mesenchymal Transition in Endometriosis.Reprod Sci. 2018 Jan;25(1):102-109. doi: 10.1177/1933719117702248. Epub 2017 Apr 25.
11 Up-regulation Of EIF3e Is Associated with The Progression of Esophageal Squamous Cell Carcinoma and Poor Prognosis in Patients.J Cancer. 2018 Mar 8;9(7):1135-1144. doi: 10.7150/jca.22546. eCollection 2018.
12 Silencing of int6 gene restores function of the ischaemic hindlimb in a rat model of peripheral arterial disease.Cardiovasc Res. 2011 Nov 1;92(2):209-17. doi: 10.1093/cvr/cvr203. Epub 2011 Jul 19.
13 c-Myc targeted regulators of cell metabolism in a transgenic mouse model of papillary lung adenocarcinoma.Oncotarget. 2016 Oct 4;7(40):65514-65539. doi: 10.18632/oncotarget.11804.
14 Decreased eIF3e Expression Can Mediate Epithelial-to-Mesenchymal Transition through Activation of the TGF Signaling Pathway.Mol Cancer Res. 2015 Oct;13(10):1421-30. doi: 10.1158/1541-7786.MCR-14-0645. Epub 2015 Jun 8.
15 Int6 expression can predict survival in early-stage non-small cell lung cancer patients.Clin Cancer Res. 2005 May 1;11(9):3198-204. doi: 10.1158/1078-0432.CCR-04-2308.
16 Expression of truncated Int6/eIF3e in mammary alveolar epithelium leads to persistent hyperplasia and tumorigenesis.Breast Cancer Res. 2007;9(4):R42. doi: 10.1186/bcr1742.
17 Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
18 GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.Nat Commun. 2017 Nov 17;8(1):1584. doi: 10.1038/s41467-017-01490-8.
19 Mammalian tumor suppressor Int6 specifically targets hypoxia inducible factor 2 alpha for degradation by hypoxia- and pVHL-independent regulation.J Biol Chem. 2007 Apr 27;282(17):12707-16. doi: 10.1074/jbc.M700423200. Epub 2007 Feb 26.
20 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
21 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.
22 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
23 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.
24 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.
25 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.
26 Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation. Respir Res. 2005 Aug 8;6(1):89. doi: 10.1186/1465-9921-6-89.
27 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.
28 Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
29 Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.