Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVRPC5X)

• DOT Name: Ubiquitin-like-conjugating enzyme ATG10 (ATG10)
• Synonyms: EC 2.3.2.-; Autophagy-related protein 10; APG10-like
• Gene Name: ATG10
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Hepatocellular carcinoma
  Behcet disease
  Breast cancer
  Breast neoplasm
  Laryngeal carcinoma
  Lung cancer
  Lung carcinoma
  Neurodegeneration with brain iron accumulation 5
  Non-small-cell lung cancer
  Oral cavity carcinoma
  Pharynx cancer
  West syndrome
  Breast carcinoma
  Chronic graft versus host disease
  Graft-versus-host disease
  Tuberculosis
  Head-neck squamous cell carcinoma
  Melanoma
  Neoplasm
  Oral cancer
• UniProt ID: ATG10_HUMAN
• EC Number: 2.3.2.-
• Pfam ID: PF03987
• Sequence:
  MEEDEFIGEKTFQRYCAEFIKHSQQIGDSWEWRPSKDCSDGYMCKIHFQIKNGSVMSHLG
  ASTHGQTCLPMEEAFELPLDDCEVIETAAASEVIKYEYHVLYSCSYQVPVLYFRASFLDG
  RPLTLKDIWEGVHECYKMRLLQGPWDTITQQEHPILGQPFFVLHPCKTNEFMTPVLKNSQ
  KINKNVNYITSWLSIVGPVVGLNLPLSYAKATSQDERNVP
• Function: E2-like enzyme involved in autophagy. Acts as an E2-like enzyme that catalyzes the conjugation of ATG12 to ATG5. ATG12 conjugation to ATG5 is required for autophagy. Likely serves as an ATG5-recognition molecule. Not involved in ATG12 conjugation to ATG3. Plays a role in adenovirus-mediated cell lysis.
• KEGG Pathway:
  Autophagy - other (hsa04136)
  Autophagy - animal (hsa04140)
• Reactome Pathway: Macroautophagy (R-HSA-1632852)

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Definitive	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Definitive	Genetic Variation	[2]
Behcet disease	DISSYMBS	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Laryngeal carcinoma	DISNHCIV	Strong	Genetic Variation	[5]
Lung cancer	DISCM4YA	Strong	Altered Expression	[6]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[6]
Neurodegeneration with brain iron accumulation 5	DISW9SFJ	Strong	Biomarker	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[6]
Oral cavity carcinoma	DISZXMVL	Strong	Genetic Variation	[5]
Pharynx cancer	DISXLF8Z	Strong	Genetic Variation	[5]
West syndrome	DISLIAU9	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[4]
Chronic graft versus host disease	DIS1MM9J	moderate	Genetic Variation	[8]
Graft-versus-host disease	DIS0QADF	moderate	Biomarker	[8]
Tuberculosis	DIS2YIMD	Disputed	Genetic Variation	[9]
Head-neck squamous cell carcinoma	DISF7P24	Limited	Genetic Variation	[5]
Melanoma	DIS1RRCY	Limited	Biomarker	[10]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[11]
Oral cancer	DISLD42D	Limited	Genetic Variation	[5]

9 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 Ubiquitin-like-conjugating enzyme ATG10 (ATG10).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ubiquitin-like-conjugating enzyme ATG10 (ATG10).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ubiquitin-like-conjugating enzyme ATG10 (ATG10).	[14]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ubiquitin-like-conjugating enzyme ATG10 (ATG10).	[15]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Ubiquitin-like-conjugating enzyme ATG10 (ATG10).	[17]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Ubiquitin-like-conjugating enzyme ATG10 (ATG10).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ubiquitin-like-conjugating enzyme ATG10 (ATG10).	[19]
AT7519	DMCE08M	Phase 1	AT7519 decreases the expression of Ubiquitin-like-conjugating enzyme ATG10 (ATG10).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ubiquitin-like-conjugating enzyme ATG10 (ATG10).	[21]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ubiquitin-like-conjugating enzyme ATG10 (ATG10).	[16]

References

• [1] Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis.PLoS One. 2012;7(12):e52705. doi: 10.1371/journal.pone.0052705. Epub 2012 Dec 20.
• [2] Functional variants of autophagy-related genes are associated with the development of hepatocellular carcinoma.Life Sci. 2019 Oct 15;235:116675. doi: 10.1016/j.lfs.2019.116675. Epub 2019 Jul 21.
• [3] Association of ATG5 Gene Polymorphisms With Behet's Disease and ATG10 Gene Polymorphisms With VKH Syndrome in a Chinese Han Population.Invest Ophthalmol Vis Sci. 2015 Dec;56(13):8280-7. doi: 10.1167/iovs.15-18035.
• [4] A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer.Nat Genet. 2018 Jul;50(7):968-978. doi: 10.1038/s41588-018-0132-x. Epub 2018 Jun 18.
• [5] Analysis of autophagy gene polymorphisms in Spanish patients with head and neck squamous cell carcinoma.Sci Rep. 2017 Jul 31;7(1):6887. doi: 10.1038/s41598-017-07270-0.
• [6] Role of ATG10 expression quantitative trait loci in non-small cell lung cancer survival.Int J Cancer. 2016 Oct 1;139(7):1564-73. doi: 10.1002/ijc.30205. Epub 2016 Jun 15.
• [7] Childhood Dystonia-Parkinsonism Following Infantile Spasms-Clinical Clue to Diagnosis in Early Beta-Propeller Protein-Associated Neurodegeneration.Neuropediatrics. 2020 Feb;51(1):22-29. doi: 10.1055/s-0039-1696688. Epub 2019 Sep 10.
• [8] Optimal dose of rabbit thymoglobulin in conditioning regimens for unmanipulated, haploidentical, hematopoietic stem cell transplantation: Long-term outcomes of a prospective randomized trial.Cancer. 2017 Aug 1;123(15):2881-2892. doi: 10.1002/cncr.30540. Epub 2017 Mar 16.
• [9] Polymorphisms in autophagy genes and susceptibility to tuberculosis.PLoS One. 2012;7(8):e41618. doi: 10.1371/journal.pone.0041618. Epub 2012 Aug 6.
• [10] Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study.Cancer Med. 2016 Nov;5(11):3336-3345. doi: 10.1002/cam4.929. Epub 2016 Oct 17.
• [11] Potentially functional variants of autophagy-related genes are associated with the efficacy and toxicity of radiotherapy in patients with nasopharyngeal carcinoma.Mol Genet Genomic Med. 2019 Dec;7(12):e1030. doi: 10.1002/mgg3.1030. Epub 2019 Nov 6.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] 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.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [16] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [17] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [18] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [19] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [20] CDK Blockade Using AT7519 Suppresses Acute Myeloid Leukemia Cell Survival through the Inhibition of Autophagy and Intensifies the Anti-leukemic Effect of Arsenic Trioxide. Iran J Pharm Res. 2019 Fall;18(Suppl1):119-131. doi: 10.22037/ijpr.2019.112560.13827.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.