Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRA6XOB)

DOT Name Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1)
Synonyms Aminoacyl tRNA synthetase complex-interacting multifunctional protein 3; Elongation factor p18; Multisynthase complex auxiliary component p18
Gene Name EEF1E1
Related Disease
Angelman syndrome ( )
Meningioma ( )
Acute leukaemia ( )
Acute lymphocytic leukaemia ( )
Adult lymphoma ( )
Advanced cancer ( )
Bladder cancer ( )
Bone osteosarcoma ( )
Breast neoplasm ( )
Childhood acute lymphoblastic leukemia ( )
Chromosomal disorder ( )
Depression ( )
Hepatitis B virus infection ( )
Hyperparathyroidism ( )
Lassa fever ( )
Lung carcinoma ( )
Lymphoma ( )
Lymphoma, non-Hodgkin, familial ( )
Malignant soft tissue neoplasm ( )
Melanoma ( )
Myelodysplastic syndrome ( )
Non-hodgkin lymphoma ( )
Non-small-cell lung cancer ( )
Osteosarcoma ( )
Pediatric lymphoma ( )
Psoriatic arthritis ( )
Retinoblastoma ( )
Sarcoma ( )
Status epilepticus seizure ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Viral hemorrhagic fever ( )
Arterial tortuosity syndrome ( )
Breast cancer ( )
Breast carcinoma ( )
Hepatocellular carcinoma ( )
Lung cancer ( )
Neuroendocrine neoplasm ( )
Ankylosing spondylitis ( )
Familial medullary thyroid carcinoma ( )
Neuroblastoma ( )
Plasma cell myeloma ( )
UniProt ID
MCA3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2UZ8; 4BL7; 4BVX; 4BVY; 5BMU; 5Y6L
Pfam ID
PF00043
Sequence
MAAAAELSLLEKSLGLSKGNKYSAQGERQIPVLQTNNGPSLTGLTTIAAHLVKQANKEYL
LGSTAEEKAIVQQWLEYRVTQVDGHSSKNDIHTLLKDLNSYLEDKVYLTGYNFTLADILL
YYGLHRFIVDLTVQEKEKYLNVSRWFCHIQHYPGIRQHLSSVVFIKNRLYTNSH
Function Positive modulator of ATM response to DNA damage.
Tissue Specificity Down-regulated in various cancer tissues.
Reactome Pathway
Cytosolic tRNA aminoacylation (R-HSA-379716 )
Selenoamino acid metabolism (R-HSA-2408522 )

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Angelman syndrome DIS4QVXO Definitive Biomarker [1]
Meningioma DISPT4TG Definitive Genetic Variation [2]
Acute leukaemia DISDQFDI Strong Altered Expression [3]
Acute lymphocytic leukaemia DISPX75S Strong Genetic Variation [3]
Adult lymphoma DISK8IZR Strong Biomarker [4]
Advanced cancer DISAT1Z9 Strong Biomarker [5]
Bladder cancer DISUHNM0 Strong Altered Expression [6]
Bone osteosarcoma DIST1004 Strong Biomarker [7]
Breast neoplasm DISNGJLM Strong Biomarker [8]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Genetic Variation [3]
Chromosomal disorder DISM5BB5 Strong Biomarker [9]
Depression DIS3XJ69 Strong Genetic Variation [10]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [11]
Hyperparathyroidism DIS4FVAT Strong Altered Expression [12]
Lassa fever DISKFYGZ Strong Biomarker [13]
Lung carcinoma DISTR26C Strong Biomarker [14]
Lymphoma DISN6V4S Strong Biomarker [4]
Lymphoma, non-Hodgkin, familial DISCXYIZ Strong Biomarker [15]
Malignant soft tissue neoplasm DISTC6NO Strong Genetic Variation [7]
Melanoma DIS1RRCY Strong Biomarker [16]
Myelodysplastic syndrome DISYHNUI Strong Biomarker [17]
Non-hodgkin lymphoma DISS2Y8A Strong Biomarker [15]
Non-small-cell lung cancer DIS5Y6R9 Strong Genetic Variation [18]
Osteosarcoma DISLQ7E2 Strong Genetic Variation [7]
Pediatric lymphoma DIS51BK2 Strong Biomarker [4]
Psoriatic arthritis DISLWTG2 Strong Biomarker [19]
Retinoblastoma DISVPNPB Strong Biomarker [20]
Sarcoma DISZDG3U Strong Genetic Variation [7]
Status epilepticus seizure DISY3BIC Strong Genetic Variation [21]
Urinary bladder cancer DISDV4T7 Strong Altered Expression [6]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [6]
Viral hemorrhagic fever DISQEBTU Strong Genetic Variation [22]
Arterial tortuosity syndrome DISWG36B moderate Biomarker [23]
Breast cancer DIS7DPX1 moderate Biomarker [24]
Breast carcinoma DIS2UE88 moderate Biomarker [24]
Hepatocellular carcinoma DIS0J828 moderate Altered Expression [25]
Lung cancer DISCM4YA moderate Biomarker [14]
Neuroendocrine neoplasm DISNPLOO moderate Altered Expression [26]
Ankylosing spondylitis DISRC6IR Limited Biomarker [27]
Familial medullary thyroid carcinoma DIS01PWX Limited Biomarker [28]
Neuroblastoma DISVZBI4 Limited Biomarker [29]
Plasma cell myeloma DIS0DFZ0 Limited Biomarker [30]
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⏷ Show the Full List of 42 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [31]
Arsenic DMTL2Y1 Approved Arsenic increases the methylation of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [36]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [43]
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14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [32]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [33]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [34]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [35]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [37]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [38]
Diethylstilbestrol DMN3UXQ Approved Diethylstilbestrol decreases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [39]
Piroxicam DMTK234 Approved Piroxicam decreases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [40]
Sodium phenylbutyrate DMXLBCQ Approved Sodium phenylbutyrate decreases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [41]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [42]
Tamibarotene DM3G74J Phase 3 Tamibarotene decreases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [33]
Arecoline DMFJZK3 Phase 1 Arecoline decreases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [44]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [45]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1). [46]
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⏷ Show the Full List of 14 Drug(s)

References

1 UBE3A-mediated p18/LAMTOR1 ubiquitination and degradation regulate mTORC1 activity and synaptic plasticity.Elife. 2018 Jul 18;7:e37993. doi: 10.7554/eLife.37993.
2 Molecular analysis of alterations of the p18INK4c gene in human meningiomas.Neuropathol Appl Neurobiol. 2000 Feb;26(1):67-75. doi: 10.1046/j.1365-2990.2000.00219.x.
3 Homozygous deletions of cyclin-dependent kinase inhibitor genes, p16(INK4A) and p18, in childhood T cell lineage acute lymphoblastic leukemias.Leukemia. 1996 Feb;10(2):255-60.
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5 Host Tumor Suppressor p18(INK4c) Functions as a Potent Cell-Intrinsic Inhibitor of Murine Gammaherpesvirus 68 Reactivation and Pathogenesis.J Virol. 2018 Feb 26;92(6):e01604-17. doi: 10.1128/JVI.01604-17. Print 2018 Mar 15.
6 Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer.Int J Cancer. 2015 Feb 1;136(3):709-20. doi: 10.1002/ijc.29022. Epub 2014 Jul 22.
7 Alterations of the p15, p16,and p18 genes in osteosarcoma.Cancer Genet Cytogenet. 1996 Feb;86(2):136-42. doi: 10.1016/0165-4608(95)00216-2.
8 A p18 mutant defective in CDK6 binding in human breast cancer cells.Cancer Res. 1996 Oct 15;56(20):4586-9.
9 Absence of cyclin-dependent kinase inhibitor p27 or p18 increases efficiency of iPSC generation without induction of iPSC genomic instability.Cell Death Dis. 2019 Mar 20;10(4):271. doi: 10.1038/s41419-019-1502-8.
10 Reliability and Validity of a Material Resources Scale and Its Association With Depression Among Young Men Who Have Sex With Men: The P18 Cohort Study.Am J Mens Health. 2018 Sep;12(5):1384-1397. doi: 10.1177/1557988316651206. Epub 2016 May 25.
11 Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18.J Biol Chem. 2012 Jul 27;287(31):26302-11. doi: 10.1074/jbc.M112.342113. Epub 2012 Jun 8.
12 Reduced p18INK4c, p21CIP1/WAF1 and p27KIP1 mRNA levels in tumours of primary and secondary hyperparathyroidism.Clin Endocrinol (Oxf). 2004 Mar;60(3):389-93. doi: 10.1111/j.1365-2265.2004.01995.x.
13 Characterization of virulence-associated determinants in the envelope glycoprotein of Pichinde virus.Virology. 2012 Nov 10;433(1):97-103. doi: 10.1016/j.virol.2012.07.009. Epub 2012 Aug 9.
14 The expression profile and prognostic significance of eukaryotic translation elongation factors in different cancers.PLoS One. 2018 Jan 17;13(1):e0191377. doi: 10.1371/journal.pone.0191377. eCollection 2018.
15 Deletion of cyclin-dependent kinase 4 inhibitor genes P15 and P16 in non-Hodgkin's lymphoma.Blood. 1995 Oct 15;86(8):2900-5.
16 Screening of germline mutations in the CDK4, CDKN2C and TP53 genes in familial melanoma: a clinic-based population study.Int J Cancer. 1998 Sep 25;78(1):13-5. doi: 10.1002/(sici)1097-0215(19980925)78:1<13::aid-ijc3>3.0.co;2-#.
17 Hematopathological alterations of major tumor suppressor cascade, vital cell cycle inhibitors and hematopoietic niche components in experimental myelodysplasia.Chem Biol Interact. 2017 Aug 1;273:1-10. doi: 10.1016/j.cbi.2017.05.014. Epub 2017 May 23.
18 Potentially functional polymorphisms in cell cycle genes and the survival of non-small cell lung cancer in a Chinese population.Lung Cancer. 2011 Jul;73(1):32-7. doi: 10.1016/j.lungcan.2010.11.001. Epub 2010 Dec 9.
19 "Invivo self-assembled" nanoprobes for optimizing autophagy-mediated chemotherapy.Biomaterials. 2017 Oct;141:199-209. doi: 10.1016/j.biomaterials.2017.06.042. Epub 2017 Jun 30.
20 The effect of miR-340 over-expression on cell-cycle-related genes in triple-negative breast cancer cells.Eur J Cancer Care (Engl). 2017 Nov;26(6). doi: 10.1111/ecc.12496. Epub 2016 May 27.
21 Interaction of GABA(A) and GABA(B) antagonists after status epilepticus in immature rats.Epilepsy Behav. 2020 Jan;102:106683. doi: 10.1016/j.yebeh.2019.106683. Epub 2019 Nov 21.
22 Cytokine patterns in a comparative model of arenavirus haemorrhagic fever in guinea pigs.J Gen Virol. 2008 Oct;89(Pt 10):2569-2579. doi: 10.1099/vir.0.2008/002048-0.
23 Oxygen-Induced Retinopathy and Choroidopathy: In Vivo Longitudinal Observation of Vascular Changes Using OCTA.Invest Ophthalmol Vis Sci. 2018 Aug 1;59(10):3932-3942. doi: 10.1167/iovs.18-24320.
24 Indolo-pyrido-isoquinolin based alkaloid inhibits growth, invasion and migration of breast cancer cells via activation ofp53-miR34a axis.Mol Oncol. 2016 Aug;10(7):1118-32. doi: 10.1016/j.molonc.2016.04.003. Epub 2016 May 20.
25 Alterations in Eukaryotic Elongation Factor complex proteins (EEF1s) in cancer and their implications in epigenetic regulation.Life Sci. 2019 Dec 1;238:116977. doi: 10.1016/j.lfs.2019.116977. Epub 2019 Oct 19.
26 A gene that encodes for a leukemia-associated phosphoprotein (p18) maps to chromosome bands 1p35-36.1.Genes Chromosomes Cancer. 1990 Jul;2(2):125-9. doi: 10.1002/gcc.2870020208.
27 Screening of underlying genetic biomarkers for ankylosing spondylitis.Mol Med Rep. 2019 Jun;19(6):5263-5274. doi: 10.3892/mmr.2019.10188. Epub 2019 Apr 24.
28 Synergistic effect of oncogenic RET and loss of p18 on medullary thyroid carcinoma development.Cancer Res. 2008 Mar 1;68(5):1329-37. doi: 10.1158/0008-5472.CAN-07-5754.
29 The p16 and p18 tumor suppressor genes in neuroblastoma: implications for drug resistance.Cancer Lett. 1996 Jul 12;104(2):183-92. doi: 10.1016/0304-3835(96)04250-4.
30 Frequent inactivation of the cyclin-dependent kinase inhibitor p18 by homozygous deletion in multiple myeloma cell lines: ectopic p18 expression inhibits growth and induces apoptosis.Leukemia. 2002 Jan;16(1):127-34. doi: 10.1038/sj.leu.2402328.
31 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.
32 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
33 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
34 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.
35 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.
36 Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
37 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
38 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
39 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.
40 Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
41 Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol Genomics. 2004 Jan 15;16(2):204-11.
42 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
43 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.
44 Characterization of arecoline-induced effects on cytotoxicity in normal human gingival fibroblasts by global gene expression profiling. Toxicol Sci. 2007 Nov;100(1):66-74.
45 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.
46 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.