Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG8QUXY)

• DOT Name: Autophagy-related protein 101 (ATG101)
• Gene Name: ATG101
• Related Disease:
  Advanced cancer
  Lung cancer
  Lung neoplasm
  Neoplasm
• UniProt ID: ATGA1_HUMAN
• PDB ID: 4WZG; 5C50; 5XUY; 5XV1; 5XV3; 5XV4; 5XV6; 8DO8
• Pfam ID: PF07855
• Sequence:
  MNCRSEVLEVSVEGRQVEEAMLAVLHTVLLHRSTGKFHYKKEGTYSIGTVGTQDVDCDFI
  DFTYVRVSSEELDRALRKVVGEFKDALRNSGGDGLGQMSLEFYQKKKSRWPFSDECIPWE
  VWTVKVHVVALATEQERQICREKVGEKLCEKIINIVEVMNRHEYLPKMPTQSEVDNVFDT
  GLRDVQPYLYKISFQITDALGTSVTTTMRRLIKDTLAL
• Function: Autophagy factor required for autophagosome formation. Stabilizes ATG13, protecting it from proteasomal degradation.
• 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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung neoplasm	DISVARNB	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

11 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 Autophagy-related protein 101 (ATG101).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Autophagy-related protein 101 (ATG101).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Autophagy-related protein 101 (ATG101).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Autophagy-related protein 101 (ATG101).	[6]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Autophagy-related protein 101 (ATG101).	[8]
Trovafloxacin	DM6AN32	Approved	Trovafloxacin increases the expression of Autophagy-related protein 101 (ATG101).	[9]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Autophagy-related protein 101 (ATG101).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Autophagy-related protein 101 (ATG101).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Autophagy-related protein 101 (ATG101).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Autophagy-related protein 101 (ATG101).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Autophagy-related protein 101 (ATG101).	[14]

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 Autophagy-related protein 101 (ATG101).	[7]

References

• [1] Autophagic Flux Is Regulated by Interaction Between the C-terminal Domain of PATCHED1 and ATG101.Mol Cancer Res. 2018 May;16(5):909-919. doi: 10.1158/1541-7786.MCR-17-0597. Epub 2018 Feb 16.
• [2] Bronchial airway gene expression signatures in mouse lung squamous cell carcinoma and their modulation by cancer chemopreventive agents.Oncotarget. 2017 Mar 21;8(12):18885-18900. doi: 10.18632/oncotarget.13806.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] TNF enhances trovafloxacin-induced in vitro hepatotoxicity by inhibiting protective autophagy. Toxicol Lett. 2021 May 15;342:73-84. doi: 10.1016/j.toxlet.2021.02.009. Epub 2021 Feb 17.
• [10] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [11] 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.
• [12] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.