Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDUYR4U)

• DOT Name: Myosin light chain 1/3, skeletal muscle isoform (MYL1)
• Synonyms: MLC1/MLC3; MLC1F/MLC3F; Myosin light chain alkali 1/2; Myosin light chain A1/A2
• Gene Name: MYL1
• Related Disease:
  Hypertrophic cardiomyopathy
  Rhabdomyosarcoma
  Congenital myopathy with reduced type 2 muscle fibers
  Congenital myopathy
• UniProt ID: MYL1_HUMAN
• Sequence:
  MAPKKDVKKPVAAAAAAPAPAPAPAPAPAPAKPKEEKIDLSAIKIEFSKEQQDEFKEAFL
  LFDRTGDSKITLSQVGDVLRALGTNPTNAEVRKVLGNPSNEELNAKKIEFEQFLPMMQAI
  SNNKDQATYEDFVEGLRVFDKEGNGTVMGAELRHVLATLGEKMKEEEVEALMAGQEDSNG
  CINYEAFVKHIMSI
• Function: Non-regulatory myosin light chain required for proper formation and/or maintenance of myofibers, and thus appropriate muscle function.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway: Striated Muscle Contraction (R-HSA-390522)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Biomarker	[1]
Rhabdomyosarcoma	DISNR7MS	Strong	Biomarker	[2]
Congenital myopathy with reduced type 2 muscle fibers	DISPSNW4	Supportive	Autosomal recessive	[3]
Congenital myopathy	DISLSK9G	Limited	Autosomal recessive	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Myosin light chain 1/3, skeletal muscle isoform (MYL1).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Myosin light chain 1/3, skeletal muscle isoform (MYL1).	[6]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Myosin light chain 1/3, skeletal muscle isoform (MYL1).	[7]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Myosin light chain 1/3, skeletal muscle isoform (MYL1).	[8]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Myosin light chain 1/3, skeletal muscle isoform (MYL1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Norepinephrine	DMOUC09	Approved	Norepinephrine increases the phosphorylation of Myosin light chain 1/3, skeletal muscle isoform (MYL1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Myosin light chain 1/3, skeletal muscle isoform (MYL1).	[10]

References

• [1] Molecular genetic basis of hypertrophic cardiomyopathy: genetic markers for sudden cardiac death.J Cardiovasc Electrophysiol. 1998 Jan;9(1):88-99. doi: 10.1111/j.1540-8167.1998.tb00871.x.
• [2] JARID2 is a direct target of the PAX3-FOXO1 fusion protein and inhibits myogenic differentiation of rhabdomyosarcoma cells.Oncogene. 2014 Feb 27;33(9):1148-57. doi: 10.1038/onc.2013.46. Epub 2013 Feb 25.
• [3] Bi-allelic mutations in MYL1 cause a severe congenital myopathy. Hum Mol Genet. 2018 Dec 15;27(24):4263-4272. doi: 10.1093/hmg/ddy320.
• [4] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [8] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [9] Role of protein kinase D1 in vasoconstriction and haemodynamics in rats. Microvasc Res. 2024 Mar;152:104627. doi: 10.1016/j.mvr.2023.104627. Epub 2023 Nov 12.
• [10] 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.
• [11] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.