Details of Drug Off-Target (DOT)

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

• DOT Name: LysM and putative peptidoglycan-binding domain-containing protein 4 (LYSMD4)
• Gene Name: LYSMD4
• Related Disease: Chronic obstructive pulmonary disease
• UniProt ID: LYSM4_HUMAN
• Sequence:
  MRHEELLTKTFQGPAVVCGTPTSHVYMFKNGSGDSGDSSEEESHRVVLRPRGKERHKSGV
  HQPPQAGAGDVVLLQRELAQEDSLNKLALQYGCKVADIKKVNNFIREQDLYALKSVKIPV
  RNHGILMETHKELKPLLSPSSETTVTVELPEADRAGAGTGAQAGQLMGFFKGIDQDIERA
  VQSEIFLHESYCMDTSHQPLLPAPPKTPMDGADCGIQWWNAVFIMLLIGIVLPVFYLVYF
  KIQASGETPNSLNTTVIPNGSMAMGTVPGQAPRLAVAVPAVTSADSQFSQTTQAGS

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	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 LysM and putative peptidoglycan-binding domain-containing protein 4 (LYSMD4).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of LysM and putative peptidoglycan-binding domain-containing protein 4 (LYSMD4).	[9]

7 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 LysM and putative peptidoglycan-binding domain-containing protein 4 (LYSMD4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of LysM and putative peptidoglycan-binding domain-containing protein 4 (LYSMD4).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of LysM and putative peptidoglycan-binding domain-containing protein 4 (LYSMD4).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of LysM and putative peptidoglycan-binding domain-containing protein 4 (LYSMD4).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of LysM and putative peptidoglycan-binding domain-containing protein 4 (LYSMD4).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of LysM and putative peptidoglycan-binding domain-containing protein 4 (LYSMD4).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of LysM and putative peptidoglycan-binding domain-containing protein 4 (LYSMD4).	[10]

References

• [1] A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.BMC Genet. 2015 Dec 3;16:138. doi: 10.1186/s12863-015-0299-4.
• [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] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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] 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.
• [10] 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.