Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSN3KG4)

• DOT Name: Transmembrane protein 59-like (TMEM59L)
• Synonyms: Brain-specific membrane-anchored protein
• Gene Name: TMEM59L
• Related Disease:
  Dental caries
  Mixed anxiety and depressive disorder
• UniProt ID: TM59L_HUMAN
• Pfam ID: PF12280
• Sequence:
  MAAVALMPPPLLLLLLLASPPAASAPSARDPFAPQLGDTQNCQLRCRDRDLGPQPSQAGL
  EGASESPYDRAVLISACERGCRLFSICRFVARSSKPNATQTECEAACVEAYVKEAEQQAC
  SHGCWSQPAEPEPEQKRKVLEAPSGALSLLDLFSTLCNDLVNSAQGFVSSTWTYYLQTDN
  GKVVVFQTQPIVESLGFQGGRLQRVEVTWRGSHPEALEVHVDPVGPLDKVRKAKIRVKTS
  SKAKVESEEPQDNDFLSCMSRRSGLPRWILACCLFLSVLVMLWLSCSTLVTAPGQHLKFQ
  PLTLEQHKGFMMEPDWPLYPPPSHACEDSLPPYKLKLDLTKL
• Function: Modulates the O-glycosylation and complex N-glycosylation steps occurring during the Golgi maturation of APP. Inhibits APP transport to the cell surface and further shedding.
• Tissue Specificity: Expressed preferentially at high level in the brain.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dental caries	DISRBCMD	Strong	Genetic Variation	[1]
Mixed anxiety and depressive disorder	DISV809X	Strong	Biomarker	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Transmembrane protein 59-like (TMEM59L) decreases the response to substance of Arsenic trioxide.	[11]

7 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 Transmembrane protein 59-like (TMEM59L).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 59-like (TMEM59L).	[4]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Transmembrane protein 59-like (TMEM59L).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transmembrane protein 59-like (TMEM59L).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transmembrane protein 59-like (TMEM59L).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Transmembrane protein 59-like (TMEM59L).	[9]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Transmembrane protein 59-like (TMEM59L).	[10]

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 Transmembrane protein 59-like (TMEM59L).	[5]

References

• [1] Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.Nat Commun. 2019 Jun 24;10(1):2773. doi: 10.1038/s41467-019-10630-1.
• [2] The Neuron-Specific Protein TMEM59L Mediates Oxidative Stress-Induced Cell Death.Mol Neurobiol. 2017 Aug;54(6):4189-4200. doi: 10.1007/s12035-016-9997-9. Epub 2016 Jun 21.
• [3] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] 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.
• [6] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 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] 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.
• [9] 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.
• [10] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [11] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.