Details of Drug Off-Target (DOT)

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

DOT Name Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3)
Synonyms eIF-4-gamma 3; eIF-4G 3; eIF4G 3; eIF-4-gamma II; eIF4GII
Gene Name EIF4G3
Related Disease
B-cell lymphoma ( )
Male infertility ( )
Neoplasm ( )
Gastric cancer ( )
Stomach cancer ( )
UniProt ID
IF4G3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1HU3
Pfam ID
PF02847 ; PF02854 ; PF02020
Sequence
MNSQPQTRSPFFQRPQIQPPRATIPNSSPSIRPGAQTPTAVYQANQHIMMVNHLPMPYPV
PQGPQYCIPQYRHSGPPYVGPPQQYPVQPPGPGPFYPGPGPGDFPNAYGTPFYPSQPVYQ
SAPIIVPTQQQPPPAKREKKTIRIRDPNQGGKDITEEIMSGGGSRNPTPPIGRPTSTPTP
PQQLPSQVPEHSPVVYGTVESAHLAASTPVTAASDQKQEEKPKPDPVLKSPSPVLRLVLS
GEKKEQEGQTSETTAIVSIAELPLPPSPTTVSSVARSTIAAPTSSALSSQPIFTTAIDDR
CELSSPREDTIPIPSLTSCTETSDPLPTNENDDDICKKPCSVAPNDIPLVSSTNLINEIN
GVSEKLSATESIVEIVKQEVLPLTLELEILENPPEEMKLECIPAPITPSTVPSFPPTPPT
PPASPPHTPVIVPAAATTVSSPSAAITVQRVLEEDESIRTCLSEDAKEIQNKIEVEADGQ
TEEILDSQNLNSRRSPVPAQIAITVPKTWKKPKDRTRTTEEMLEAELELKAEEELSIDKV
LESEQDKMSQGFHPERDPSDLKKVKAVEENGEEAEPVRNGAESVSEGEGIDANSGSTDSS
GDGVTFPFKPESWKPTDTEGKKQYDREFLLDFQFMPACIQKPEGLPPISDVVLDKINQPK
LPMRTLDPRILPRGPDFTPAFADFGRQTPGGRGVPLLNVGSRRSQPGQRREPRKIITVSV
KEDVHLKKAENAWKPSQKRDSQADDPENIKTQELFRKVRSILNKLTPQMFNQLMKQVSGL
TVDTEERLKGVIDLVFEKAIDEPSFSVAYANMCRCLVTLKVPMADKPGNTVNFRKLLLNR
CQKEFEKDKADDDVFEKKQKELEAASAPEERTRLHDELEEAKDKARRRSIGNIKFIGELF
KLKMLTEAIMHDCVVKLLKNHDEESLECLCRLLTTIGKDLDFEKAKPRMDQYFNQMEKIV
KERKTSSRIRFMLQDVIDLRLCNWVSRRADQGPKTIEQIHKEAKIEEQEEQRKVQQLMTK
EKRRPGVQRVDEGGWNTVQGAKNSRVLDPSKFLKITKPTIDEKIQLVPKAQLGSWGKGSS
GGAKASETDALRSSASSLNRFSALQPPAPSGSTPSTPVEFDSRRTLTSRGSMGREKNDKP
LPSATARPNTFMRGGSSKDLLDNQSQEEQRREMLETVKQLTGGVDVERNSTEAERNKTRE
SAKPEISAMSAHDKAALSEEELERKSKSIIDEFLHINDFKEAMQCVEELNAQGLLHVFVR
VGVESTLERSQITRDHMGQLLYQLVQSEKLSKQDFFKGFSETLELADDMAIDIPHIWLYL
AELVTPMLKEGGISMRELTIEFSKPLLPVGRAGVLLSEILHLLCKQMSHKKVGALWREAD
LSWKDFLPEGEDVHNFLLEQKLDFIESDSPCSSEALSKKELSAEELYKRLEKLIIEDKAN
DEQIFDWVEANLDEIQMSSPTFLRALMTAVCKAAIIADSSTFRVDTAVIKQRVPILLKYL
DSDTEKELQALYALQASIVKLDQPANLLRMFFDCLYDEEVISEDAFYKWESSKDPAEQNG
KGVALKSVTAFFTWLREAEEESEDN
Function
Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome. Functional homolog of EIF4G1.
KEGG Pathway
Viral myocarditis (hsa05416 )
Reactome Pathway
ISG15 antiviral mechanism (R-HSA-1169408 )

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
B-cell lymphoma DISIH1YQ Strong Altered Expression [1]
Male infertility DISY3YZZ Strong Genetic Variation [2]
Neoplasm DISZKGEW Strong Biomarker [1]
Gastric cancer DISXGOUK Limited Biomarker [3]
Stomach cancer DISKIJSX Limited Biomarker [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas 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 4 gamma 3 (EIF4G3). [4]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [5]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [8]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [9]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [10]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [11]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [12]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [11]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [14]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [15]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [17]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [18]
Coumestrol DM40TBU Investigative Coumestrol decreases the expression of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [20]
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⏷ Show the Full List of 15 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
DNCB DMDTVYC Phase 2 DNCB affects the binding of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [13]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [16]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Eukaryotic translation initiation factor 4 gamma 3 (EIF4G3). [19]
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References

1 Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development.PLoS Genet. 2014 Jan 30;10(1):e1004105. doi: 10.1371/journal.pgen.1004105. eCollection 2014 Jan.
2 Nuclear localization of EIF4G3 suggests a role for the XY body in translational regulation during spermatogenesis in mice.Biol Reprod. 2018 Jan 1;98(1):102-114. doi: 10.1093/biolre/iox150.
3 Circ-EIF4G3 promotes the development of gastric cancer by sponging miR-335.Pathol Res Pract. 2019 Sep;215(9):152507. doi: 10.1016/j.prp.2019.152507. Epub 2019 Jun 20.
4 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.
5 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
6 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
10 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.
11 Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
12 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
13 Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
14 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
15 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.
16 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.
17 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
18 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
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 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.