Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD3R434)

DOT Name	Protein argonaute-1 (AGO1)
Synonyms	Argonaute1; hAgo1; Argonaute RISC catalytic component 1; Eukaryotic translation initiation factor 2C 1; eIF-2C 1; eIF2C 1; Putative RNA-binding protein Q99
Gene Name	AGO1
Related Disease	Alcohol dependence ( ) Alzheimer disease ( ) Attention deficit hyperactivity disorder ( ) Colon cancer ( ) Colon carcinoma ( ) Hepatitis C virus infection ( ) Hepatocellular carcinoma ( ) Hidradenitis suppurativa ( ) Malignant mesothelioma ( ) Neoplasm ( ) Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures ( ) Precancerous condition ( ) Skin cancer ( ) Autism ( ) Bladder cancer ( ) Intellectual disability ( ) Advanced cancer ( ) Carcinoma ( ) Chronic hepatitis B virus infection ( ) Epithelial ovarian cancer ( ) Graves disease ( ) Hepatitis B virus infection ( ) Lung cancer ( ) Lung carcinoma ( ) Metastatic malignant neoplasm ( ) Neuroblastoma ( ) Ovarian cancer ( )
UniProt ID	AGO1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1SI2; 1SI3; 4KRE; 4KRF; 4KXT; 5W6V
Pfam ID	PF08699 ; PF16488 ; PF16487 ; PF16486 ; PF02170 ; PF02171
Sequence	MEAGPSGAAAGAYLPPLQQVFQAPRRPGIGTVGKPIKLLANYFEVDIPKIDVYHYEVDIK PDKCPRRVNREVVEYMVQHFKPQIFGDRKPVYDGKKNIYTVTALPIGNERVDFEVTIPGE GKDRIFKVSIKWLAIVSWRMLHEALVSGQIPVPLESVQALDVAMRHLASMRYTPVGRSFF SPPEGYYHPLGGGREVWFGFHQSVRPAMWKMMLNIDVSATAFYKAQPVIEFMCEVLDIRN IDEQPKPLTDSQRVRFTKEIKGLKVEVTHCGQMKRKYRVCNVTRRPASHQTFPLQLESGQ TVECTVAQYFKQKYNLQLKYPHLPCLQVGQEQKHTYLPLEVCNIVAGQRCIKKLTDNQTS TMIKATARSAPDRQEEISRLMKNASYNLDPYIQEFGIKVKDDMTEVTGRVLPAPILQYGG RNRAIATPNQGVWDMRGKQFYNGIEIKVWAIACFAPQKQCREEVLKNFTDQLRKISKDAG MPIQGQPCFCKYAQGADSVEPMFRHLKNTYSGLQLIIVILPGKTPVYAEVKRVGDTLLGM ATQCVQVKNVVKTSPQTLSNLCLKINVKLGGINNILVPHQRSAVFQQPVIFLGADVTHPP AGDGKKPSITAVVGSMDAHPSRYCATVRVQRPRQEIIEDLSYMVRELLIQFYKSTRFKPT RIIFYRDGVPEGQLPQILHYELLAIRDACIKLEKDYQPGITYIVVQKRHHTRLFCADKNE RIGKSGNIPAGTTVDTNITHPFEFDFYLCSHAGIQGTSRPSHYYVLWDDNRFTADELQIL TYQLCHTYVRCTRSVSIPAPAYYARLVAFRARYHLVDKEHDSGEGSHISGQSNGRDPQAL AKAVQVHQDTLRTMYFA
Function	Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs).
Reactome Pathway	MicroRNA (miRNA) biogenesis (R-HSA-203927 ) Oxidative Stress Induced Senescence (R-HSA-2559580 ) Oncogene Induced Senescence (R-HSA-2559585 ) Ca2+ pathway (R-HSA-4086398 ) Small interfering RNA (siRNA) biogenesis (R-HSA-426486 ) Post-transcriptional silencing by small RNAs (R-HSA-426496 ) Transcriptional regulation by small RNAs (R-HSA-5578749 ) TP53 Regulates Metabolic Genes (R-HSA-5628897 ) MAPK6/MAPK4 signaling (R-HSA-5687128 ) Transcriptional Regulation by VENTX (R-HSA-8853884 ) Regulation of RUNX1 Expression and Activity (R-HSA-8934593 ) RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function (R-HSA-8936459 ) Regulation of PTEN mRNA translation (R-HSA-8943723 ) Competing endogenous RNAs (ceRNAs) regulate PTEN translation (R-HSA-8948700 ) Transcriptional Regulation by MECP2 (R-HSA-8986944 ) Estrogen-dependent gene expression (R-HSA-9018519 ) Regulation of MECP2 expression and activity (R-HSA-9022692 ) NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux (R-HSA-9029569 ) Regulation of CDH11 mRNA translation by microRNAs (R-HSA-9759811 ) Regulation of NPAS4 mRNA translation (R-HSA-9768778 ) Pre-NOTCH Transcription and Translation (R-HSA-1912408 )

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[3]
Colon cancer	DISVC52G	Strong	Biomarker	[4]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[4]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Hidradenitis suppurativa	DIS3ZNAK	Strong	Biomarker	[7]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[9]
Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures	DISN067Z	Strong	Autosomal dominant	[10]
Precancerous condition	DISV06FL	Strong	Biomarker	[11]
Skin cancer	DISTM18U	Strong	Biomarker	[11]
Autism	DISV4V1Z	moderate	Biomarker	[12]
Bladder cancer	DISUHNM0	moderate	Altered Expression	[13]
Intellectual disability	DISMBNXP	moderate	Genetic Variation	[14]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[15]
Carcinoma	DISH9F1N	Limited	Altered Expression	[16]
Chronic hepatitis B virus infection	DISHL4NT	Limited	Genetic Variation	[17]
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[16]
Graves disease	DISU4KOQ	Limited	Altered Expression	[18]
Hepatitis B virus infection	DISLQ2XY	Limited	Genetic Variation	[17]
Lung cancer	DISCM4YA	Limited	Biomarker	[15]
Lung carcinoma	DISTR26C	Limited	Biomarker	[15]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[16]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[19]
Ovarian cancer	DISZJHAP	Limited	Altered Expression	[16]
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⏷ Show the Full List of 27 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

12 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 Protein argonaute-1 (AGO1).	[20]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein argonaute-1 (AGO1).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein argonaute-1 (AGO1).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein argonaute-1 (AGO1).	[23]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Protein argonaute-1 (AGO1).	[24]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein argonaute-1 (AGO1).	[25]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein argonaute-1 (AGO1).	[26]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein argonaute-1 (AGO1).	[27]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protein argonaute-1 (AGO1).	[28]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Protein argonaute-1 (AGO1).	[29]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein argonaute-1 (AGO1).	[30]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Protein argonaute-1 (AGO1).	[31]
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⏷ Show the Full List of 12 Drug(s)

References

1	Association of microRNA biogenesis pathway gene variants and alcohol dependence risk.DNA Cell Biol. 2015 Mar;34(3):220-6. doi: 10.1089/dna.2014.2549. Epub 2014 Dec 11.
2	Microbiome-Mediated Upregulation of MicroRNA-146a in Sporadic Alzheimer's Disease.Front Neurol. 2018 Mar 19;9:145. doi: 10.3389/fneur.2018.00145. eCollection 2018.
3	Regulating the Regulators in Attention-Deficit/Hyperactivity Disorder: A Genetic Association Study of microRNA Biogenesis Pathways.OMICS. 2017 Jun;21(6):352-358. doi: 10.1089/omi.2017.0048. Epub 2017 May 30.
4	Screening for possible miRNA-mRNA associations in a colon cancer cell line.Gene. 2014 Jan 10;533(2):520-31. doi: 10.1016/j.gene.2013.08.005. Epub 2013 Aug 9.
5	MicroRNA-122 dependent binding of Ago2 protein to hepatitis C virus RNA is associated with enhanced RNA stability and translation stimulation.PLoS One. 2013;8(2):e56272. doi: 10.1371/journal.pone.0056272. Epub 2013 Feb 6.
6	AGO1 may influence the prognosis of hepatocellular carcinoma through TGF- pathway.Cell Death Dis. 2018 Feb 27;9(3):324. doi: 10.1038/s41419-018-0338-y.
7	The microRNA effector RNA-induced silencing complex in hidradenitis suppurativa: a significant dysregulation within active inflammatory lesions.Arch Dermatol Res. 2017 Sep;309(7):557-565. doi: 10.1007/s00403-017-1752-1. Epub 2017 Jun 20.
8	MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos-related pleural effusion.Biomed Res Int. 2015;2015:635748. doi: 10.1155/2015/635748. Epub 2015 Feb 1.
9	The stem cell E3-ligase Lin-41 promotes liver cancer progression through inhibition of microRNA-mediated gene silencing.J Pathol. 2013 Feb;229(3):486-96. doi: 10.1002/path.4130.
10	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
11	Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components argonaute-1, argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer.Mol Carcinog. 2012 Nov;51(11):916-22. doi: 10.1002/mc.20861. Epub 2011 Oct 24.
12	Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder.Cell Rep. 2018 Jan 16;22(3):734-747. doi: 10.1016/j.celrep.2017.12.074.
13	Diagnostic and Prognostic Potential of MicroRNA Maturation Regulators Drosha, AGO1 and AGO2 in Urothelial Carcinomas of the Bladder.Int J Mol Sci. 2018 May 31;19(6):1622. doi: 10.3390/ijms19061622.
14	Further evidence of a causal association between AGO1, a critical regulator of microRNA formation, and intellectual disability/autism spectrum disorder.Eur J Med Genet. 2019 Jun;62(6):103537. doi: 10.1016/j.ejmg.2018.09.004. Epub 2018 Sep 11.
15	Targeting high transcriptional control activity of long mononucleotide A-T repeats in cancer by Argonaute 1.Gene. 2019 May 30;699:54-61. doi: 10.1016/j.gene.2019.03.010. Epub 2019 Mar 9.
16	Argonaute, Dicer, and Drosha are up-regulated along tumor progression in serous ovarian carcinoma.Hum Pathol. 2012 Nov;43(11):2062-9. doi: 10.1016/j.humpath.2012.02.016. Epub 2012 May 29.
17	Association between SNPs in miRNA-machinery genes and chronic hepatitis B in the Chinese Han population.Infect Genet Evol. 2014 Dec;28:113-7. doi: 10.1016/j.meegid.2014.09.015. Epub 2014 Sep 17.
18	Polymorphisms and expression of genes encoding Argonautes 1 and 2 in autoimmune thyroid diseases.Autoimmunity. 2018 Feb;51(1):35-42. doi: 10.1080/08916934.2017.1416468. Epub 2017 Dec 19.
19	Ago1 and Ago2 differentially affect cell proliferation, motility and apoptosis when overexpressed in SH-SY5Y neuroblastoma cells.FEBS Lett. 2011 Oct 3;585(19):2965-71. doi: 10.1016/j.febslet.2011.08.003. Epub 2011 Aug 11.
20	A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
21	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.
22	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.
23	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.
24	Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
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	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.
27	Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
28	Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
29	Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
30	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
31	Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.