Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFQ44V2)

• DOT Name: Microtubule-associated proteins 1A/1B light chain 3 beta 2 (MAP1LC3B2)
• Synonyms: Microtubule-associated proteins 1A/1B light chain 3B-like
• Gene Name: MAP1LC3B2
• Related Disease: Nasopharyngeal carcinoma
• UniProt ID: MP3B2_HUMAN
• Pfam ID: PF02991
• Sequence:
  MPSEKTFKQRRTFEQRVEDVRLIREQHPTKIPVIIERYKGEKQLPVLDKTKFLVPDHVNM
  SELIKIIRRRLQLNANQAFFLLVNGHSMVSVSTPISEVYESEKDEDGFLYMVCASQETFG
  MKLSV
• Function: Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). Plays a role in mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. In response to cellular stress and upon mitochondria fission, binds C-18 ceramides and anchors autophagolysosomes to outer mitochondrial membranes to eliminate damaged mitochondria. While LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation.
• KEGG Pathway:
  Mitophagy - animal (hsa04137)
  Autophagy - animal (hsa04140)
  Ferroptosis (hsa04216)
  Apelin sig.ling pathway (hsa04371)
  NOD-like receptor sig.ling pathway (hsa04621)
  Amyotrophic lateral sclerosis (hsa05014)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Shigellosis (hsa05131)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Microtubule-associated proteins 1A/1B light chain 3 beta 2 (MAP1LC3B2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Microtubule-associated proteins 1A/1B light chain 3 beta 2 (MAP1LC3B2).	[7]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Microtubule-associated proteins 1A/1B light chain 3 beta 2 (MAP1LC3B2).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Microtubule-associated proteins 1A/1B light chain 3 beta 2 (MAP1LC3B2).	[4]
Trovafloxacin	DM6AN32	Approved	Trovafloxacin increases the expression of Microtubule-associated proteins 1A/1B light chain 3 beta 2 (MAP1LC3B2).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Microtubule-associated proteins 1A/1B light chain 3 beta 2 (MAP1LC3B2).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Microtubule-associated proteins 1A/1B light chain 3 beta 2 (MAP1LC3B2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Microtubule-associated proteins 1A/1B light chain 3 beta 2 (MAP1LC3B2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Microtubule-associated proteins 1A/1B light chain 3 beta 2 (MAP1LC3B2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Microtubule-associated proteins 1A/1B light chain 3 beta 2 (MAP1LC3B2).	[11]

References

• [1] A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.Nat Genet. 2010 Jul;42(7):599-603. doi: 10.1038/ng.601. Epub 2010 May 30.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [9] 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.
• [10] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [11] 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.