Details of Drug Off-Target (DOT)

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

• DOT Name: Autophagy-related protein 13 (ATG13)
• Gene Name: ATG13
• Related Disease:
  Acute myocardial infarction
  Arteriosclerosis
  Atherosclerosis
  Cerebral infarction
  Neoplasm
  Parkinson disease
  Hepatocellular carcinoma
• UniProt ID: ATG13_HUMAN
• PDB ID: 3WAN; 3WAO; 3WAP; 5C50; 5XUY; 5XV1; 5XV3; 5XV4; 5XV6; 6HYN; 8DO8; 8SOI; 8SQZ; 8SRM; 8SRQ
• Pfam ID: PF10033
• Sequence:
  METDLNSQDRKDLDKFIKFFALKTVQVIVQARLGEKICTRSSSSPTGSDWFNLAIKDIPE
  VTHEAKKALAGQLPAVGRSMCVEISLKTSEGDSMELEIWCLEMNEKCDKEIKVSYTVYNR
  LSLLLKSLLAITRVTPAYRLSRKQGHEYVILYRIYFGEVQLSGLGEGFQTVRVGTVGTPV
  GTITLSCAYRINLAFMSTRQFERTPPIMGIIIDHFVDRPYPSSSPMHPCNYRTAGEDTGV
  IYPSVEDSQEVCTTSFSTSPPSQLSSSRLSYQPAALGVGSADLAYPVVFAAGLNATHPHQ
  LMVPGKEGGVPLAPNQPVHGTQADQERLATCTPSDRTHCAATPSSSEDTETVSNSSEGRA
  SPHDVLETIFVRKVGAFVNKPINQVTLTSLDIPFAMFAPKNLELEDTDPMVNPPDSPETE
  SPLQGSLHSDGSSGGSSGNTHDDFVMIDFKPAFSKDDILPMDLGTFYREFQNPPQLSSLS
  IDIGAQSMAEDLDSLPEKLAVHEKNVREFDAFVETLQ
• Function: Autophagy factor required for autophagosome formation and mitophagy. Target of the TOR kinase signaling pathway that regulates autophagy through the control of the phosphorylation status of ATG13 and ULK1, and the regulation of the ATG13-ULK1-RB1CC1 complex. Through its regulation of ULK1 activity, plays a role in the regulation of the kinase activity of mTORC1 and cell proliferation.
• KEGG Pathway:
  Autophagy - other (hsa04136)
  Autophagy - animal (hsa04140)
  Longevity regulating pathway (hsa04211)
  Alzheimer disease (hsa05010)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Spinocerebellar ataxia (hsa05017)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway: Macroautophagy (R-HSA-1632852)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[1]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[2]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[2]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Disputed	Biomarker	[6]

6 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 Autophagy-related protein 13 (ATG13).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Autophagy-related protein 13 (ATG13).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Autophagy-related protein 13 (ATG13).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Autophagy-related protein 13 (ATG13).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Autophagy-related protein 13 (ATG13).	[14]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of Autophagy-related protein 13 (ATG13).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Imatinib	DM7RJXL	Approved	Imatinib increases the phosphorylation of Autophagy-related protein 13 (ATG13).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Autophagy-related protein 13 (ATG13).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Autophagy-related protein 13 (ATG13).	[13]

References

• [1] Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis.Cell Death Dis. 2018 Jun 7;9(6):694. doi: 10.1038/s41419-018-0723-6.
• [2] Recombinant Thrombomodulin Exerts Anti-autophagic Action in Endothelial Cells and Provides Anti-atherosclerosis Effect in Apolipoprotein E Deficient Mice.Sci Rep. 2017 Jun 12;7(1):3284. doi: 10.1038/s41598-017-03443-z.
• [3] Rapamycin induces autophagy to alleviate acute kidney injury following cerebral ischemia and reperfusion via the mTORC1/ATG13/ULK1 signaling pathway.Mol Med Rep. 2018 Dec;18(6):5445-5454. doi: 10.3892/mmr.2018.9586. Epub 2018 Oct 24.
• [4] Inhibition of autophagy initiation potentiates chemosensitivity in mesothelioma.Mol Carcinog. 2018 Mar;57(3):319-332. doi: 10.1002/mc.22757. Epub 2017 Nov 14.
• [5] The PARK10 gene USP24 is a negative regulator of autophagy and ULK1 protein stability.Autophagy. 2020 Jan;16(1):140-153. doi: 10.1080/15548627.2019.1598754. Epub 2019 Apr 7.
• [6] LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells.Int J Mol Med. 2018 May;41(5):2601-2608. doi: 10.3892/ijmm.2018.3499. Epub 2018 Feb 16.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Imatinib disturbs lysosomal function and morphology and impairs the activity of mTORC1 in human hepatocyte cell lines. Food Chem Toxicol. 2022 Apr;162:112869. doi: 10.1016/j.fct.2022.112869. Epub 2022 Feb 16.
• [11] Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
• [12] 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.
• [13] 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.
• [14] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [15] Suppressed translation and ULK1 degradation as potential mechanisms of autophagy limitation under prolonged starvation. Autophagy. 2016 Nov;12(11):2085-2097. doi: 10.1080/15548627.2016.1226733. Epub 2016 Sep 14.