Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH19LOA)

• DOT Name: ATP-binding cassette sub-family E member 1 (ABCE1)
• Synonyms: EC 3.6.5.-; 2'-5'-oligoadenylate-binding protein; HuHP68; RNase L inhibitor; Ribonuclease 4 inhibitor; RNS4I
• Gene Name: ABCE1
• Related Disease:
  Colorectal carcinoma
  Colorectal neoplasm
  Lung cancer
  Lung carcinoma
  Adult lymphoma
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Esophageal cancer
  Glioma
  Lung adenocarcinoma
  Lung neoplasm
  Lymphoma
  Malignant thymoma
  Neoplasm
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Oral cancer
  Pediatric lymphoma
  Prostate neoplasm
  Retinoblastoma
  Severe combined immunodeficiency
  Systemic lupus erythematosus
  Advanced cancer
  Small-cell lung cancer
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: ABCE1_HUMAN
• PDB ID: 6ZME; 6ZVJ; 7A09
• EC Number: 3.6.5.-
• Pfam ID: PF00005 ; PF00037 ; PF04068
• Sequence:
  MADKLTRIAIVNHDKCKPKKCRQECKKSCPVVRMGKLCIEVTPQSKIAWISETLCIGCGI
  CIKKCPFGALSIVNLPSNLEKETTHRYCANAFKLHRLPIPRPGEVLGLVGTNGIGKSTAL
  KILAGKQKPNLGKYDDPPDWQEILTYFRGSELQNYFTKILEDDLKAIIKPQYVDQIPKAA
  KGTVGSILDRKDETKTQAIVCQQLDLTHLKERNVEDLSGGELQRFACAVVCIQKADIFMF
  DEPSSYLDVKQRLKAAITIRSLINPDRYIIVVEHDLSVLDYLSDFICCLYGVPSAYGVVT
  MPFSVREGINIFLDGYVPTENLRFRDASLVFKVAETANEEEVKKMCMYKYPGMKKKMGEF
  ELAIVAGEFTDSEIMVMLGENGTGKTTFIRMLAGRLKPDEGGEVPVLNVSYKPQKISPKS
  TGSVRQLLHEKIRDAYTHPQFVTDVMKPLQIENIIDQEVQTLSGGELQRVALALCLGKPA
  DVYLIDEPSAYLDSEQRLMAARVVKRFILHAKKTAFVVEHDFIMATYLADRVIVFDGVPS
  KNTVANSPQTLLAGMNKFLSQLEITFRRDPNNYRPRINKLNSIKDVEQKKSGNYFFLDD
• Function: Nucleoside-triphosphatase (NTPase) involved in ribosome recycling by mediating ribosome disassembly. Able to hydrolyze ATP, GTP, UTP and CTP. Splits ribosomes into free 60S subunits and tRNA- and mRNA-bound 40S subunits. Acts either after canonical termination facilitated by release factors (ETF1/eRF1) or after recognition of stalled and vacant ribosomes by mRNA surveillance factors (PELO/Pelota). Involved in the No-Go Decay (NGD) pathway: recruited to stalled ribosomes by the Pelota-HBS1L complex, and drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway. Also plays a role in quality control of translation of mitochondrial outer membrane-localized mRNA. As part of the PINK1-regulated signaling, ubiquitinated by CNOT4 upon mitochondria damage; this modification generates polyubiquitin signals that recruit autophagy receptors to the mitochondrial outer membrane and initiate mitophagy. RNASEL-specific protein inhibitor which antagonizes the binding of 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) to RNASEL. Negative regulator of the anti-viral effect of the interferon-regulated 2-5A/RNASEL pathway ; (Microbial infection) May act as a chaperone for post-translational events during HIV-1 capsid assembly; (Microbial infection) Plays a role in the down-regulation of the 2-5A/RNASEL pathway during encephalomyocarditis virus (EMCV) and HIV-1 infections.
• Reactome Pathway:
  Interferon alpha/beta signaling (R-HSA-909733)
  OAS antiviral response (R-HSA-8983711)

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Colorectal neoplasm	DISR1UCN	Definitive	Biomarker	[1]
Lung cancer	DISCM4YA	Definitive	Altered Expression	[2]
Lung carcinoma	DISTR26C	Definitive	Altered Expression	[2]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[6]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Biomarker	[7]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[8]
Lung neoplasm	DISVARNB	Strong	Biomarker	[9]
Lymphoma	DISN6V4S	Strong	Biomarker	[3]
Malignant thymoma	DIS59MOU	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[12]
Oral cancer	DISLD42D	Strong	Biomarker	[13]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[3]
Prostate neoplasm	DISHDKGQ	Strong	Genetic Variation	[14]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[15]
Severe combined immunodeficiency	DIS6MF4Q	Strong	Biomarker	[3]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[16]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[17]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[18]
Thyroid cancer	DIS3VLDH	moderate	Biomarker	[19]
Thyroid gland carcinoma	DISMNGZ0	moderate	Biomarker	[19]
Thyroid tumor	DISLVKMD	moderate	Biomarker	[19]

14 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 ATP-binding cassette sub-family E member 1 (ABCE1).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of ATP-binding cassette sub-family E member 1 (ABCE1).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ATP-binding cassette sub-family E member 1 (ABCE1).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ATP-binding cassette sub-family E member 1 (ABCE1).	[23]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of ATP-binding cassette sub-family E member 1 (ABCE1).	[24]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP-binding cassette sub-family E member 1 (ABCE1).	[25]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of ATP-binding cassette sub-family E member 1 (ABCE1).	[26]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of ATP-binding cassette sub-family E member 1 (ABCE1).	[27]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of ATP-binding cassette sub-family E member 1 (ABCE1).	[28]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of ATP-binding cassette sub-family E member 1 (ABCE1).	[29]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP-binding cassette sub-family E member 1 (ABCE1).	[30]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of ATP-binding cassette sub-family E member 1 (ABCE1).	[31]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of ATP-binding cassette sub-family E member 1 (ABCE1).	[32]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the expression of ATP-binding cassette sub-family E member 1 (ABCE1).	[33]

References

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• [2] Tip60-siRNA regulates ABCE1 acetylation to suppress lung cancer growth via activation of the apoptotic signaling pathway.Exp Ther Med. 2019 Apr;17(4):3195-3202. doi: 10.3892/etm.2019.7302. Epub 2019 Feb 22.
• [3] Highly potent anti-CD20-RLI immunocytokine targeting established human B lymphoma in SCID mouse.MAbs. 2014 Jul-Aug;6(4):1026-37. doi: 10.4161/mabs.28699.
• [4] Dual inhibition of ABCE1 and LCP1 by microRNA-96 results in an additive effect in breast cancer mouse model.Oncotarget. 2019 Mar 12;10(21):2086-2094. doi: 10.18632/oncotarget.26747. eCollection 2019 Mar 12.
• [5] Effects of silencing the ATP-binding cassette protein E1 gene by electroporation on the proliferation and migration of EC109 human esophageal cancer cells.Mol Med Rep. 2015 Jul;12(1):837-42. doi: 10.3892/mmr.2015.3512. Epub 2015 Mar 19.
• [6] ABCE1, a member of ATP-binding cassette transporter gene, encodes peptides capable of inducing HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes in colon cancer patients.Oncol Rep. 2005 May;13(5):907-13.
• [7] Down-regulation of ABCE1 inhibits temozolomide resistance in glioma through the PI3K/Akt/NF-B signaling pathway.Biosci Rep. 2018 Dec 11;38(6):BSR20181711. doi: 10.1042/BSR20181711. Print 2018 Dec 21.
• [8] Deficiency of Functional Iron-Sulfur Domains in ABCE1 Inhibits the Proliferation and Migration of Lung Adenocarcinomas By Regulating the Biogenesis of Beta-Actin In Vitro.Cell Physiol Biochem. 2017;44(2):554-566. doi: 10.1159/000485090. Epub 2017 Nov 17.
• [9] ABCE1 plays an essential role in lung cancer progression and metastasis.Tumour Biol. 2016 Jun;37(6):8375-82. doi: 10.1007/s13277-015-4713-3. Epub 2016 Jan 5.
• [10] Diagnosis of thymic epithelial tumor subtypes by a quantitative proteomic approach.Analyst. 2018 May 29;143(11):2491-2500. doi: 10.1039/c8an00218e.
• [11] Promyelocytic leukemia zinc finger triggers ATP-binding cassette subfamily E member 1-mediated growth inhibition in breast cancer cells.Oncol Lett. 2018 Oct;16(4):4143-4150. doi: 10.3892/ol.2018.9207. Epub 2018 Jul 24.
• [12] The expression and correlation between chemokine CCL7 and ABCE1 in non-small cell lung cancer.Exp Ther Med. 2018 Oct;16(4):3004-3010. doi: 10.3892/etm.2018.6568. Epub 2018 Aug 2.
• [13] Knock-down of ABCE1 gene induces G1/S arrest in human oral cancer cells.Int J Clin Exp Pathol. 2014 Aug 15;7(9):5495-504. eCollection 2014.
• [14] RNASEL and RNASEL-inhibitor variation and prostate cancer risk in Afro-Caribbeans.Prostate. 2008 Mar 1;68(4):354-9. doi: 10.1002/pros.20687.
• [15] Genistein suppresses retinoblastoma cell viability and growth and induces apoptosis by upregulating miR-145 and inhibiting its target ABCE1.Mol Vis. 2017 Jul 3;23:385-394. eCollection 2017.
• [16] Gene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus.Mol Immunol. 2006 Mar;43(9):1497-507. doi: 10.1016/j.molimm.2005.07.039. Epub 2005 Sep 6.
• [17] Comparison of breast cancer metastasis models reveals a possible mechanism of tumor aggressiveness.Cell Death Dis. 2018 Oct 10;9(10):1040. doi: 10.1038/s41419-018-1094-8.
• [18] A small interfering ABCE1-targeting RNA inhibits the proliferation and invasiveness of small cell lung cancer.Int J Mol Med. 2010 May;25(5):687-93.
• [19] Effect of ABCE1-silencing gene, transfected by electrotransfer, on the proliferation, invasion, and migration of human thyroid carcinoma SW579 cells.Genet Mol Res. 2015 Nov 23;14(4):14680-9. doi: 10.4238/2015.November.18.32.
• [20] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [21] Benzodithiophenes potentiate differentiation of acute promyelocytic leukemia cells by lowering the threshold for ligand-mediated corepressor/coactivator exchange with retinoic acid receptor alpha and enhancing changes in all-trans-retinoic acid-regulated gene expression. Cancer Res. 2005 Sep 1;65(17):7856-65. doi: 10.1158/0008-5472.CAN-05-1056.
• [22] 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.
• [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] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [25] 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.
• [26] 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.
• [27] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [28] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [29] 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.
• [30] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [31] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [32] 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.
• [33] Defects in TLR3 expression and RNase L activation lead to decreased MnSOD expression and insulin resistance in muscle cells of obese people. Cell Death Dis. 2014 Mar 20;5(3):e1136. doi: 10.1038/cddis.2014.104.