Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7CQ24K)

• DOT Name: Myosin light chain 5 (MYL5)
• Synonyms: Myosin regulatory light chain 5; Superfast myosin regulatory light chain 2; MYLC2; MyLC-2
• Gene Name: MYL5
• Related Disease:
  Cervical cancer
  Cervical carcinoma
• UniProt ID: MYL5_HUMAN
• Pfam ID: PF13499
• Sequence:
  MASRKTKKKEGGALRAQRASSNVFSNFEQTQIQEFKEAFTLMDQNRDGFIDKEDLKDTYA
  SLGKTNVKDDELDAMLKEASGPINFTMFLNLFGEKLSGTDAEETILNAFKMLDPDGKGKI
  NKEYIKRLLMSQADKMTAEEVDQMFQFASIDVAGNLDYKALSYVITHGEEKEE
• Tissue Specificity: Expressed in fetal skeletal muscle and retina.
• KEGG Pathway:
  Axon guidance (hsa04360)
  Focal adhesion (hsa04510)
  Adherens junction (hsa04520)
  Leukocyte transendothelial migration (hsa04670)
  Regulation of actin cytoskeleton (hsa04810)
  Motor proteins (hsa04814)
  Cytoskeleton in muscle cells (hsa04820)
  Shigellosis (hsa05131)
  Salmonella infection (hsa05132)
• Reactome Pathway: Smooth Muscle Contraction (R-HSA-445355)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Strong	Altered Expression	[1]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[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 Myosin light chain 5 (MYL5).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Myosin light chain 5 (MYL5).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Myosin light chain 5 (MYL5).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Myosin light chain 5 (MYL5).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Myosin light chain 5 (MYL5).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Myosin light chain 5 (MYL5).	[6]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Myosin light chain 5 (MYL5).	[7]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Myosin light chain 5 (MYL5).	[8]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Myosin light chain 5 (MYL5).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Myosin light chain 5 (MYL5).	[10]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Myosin light chain 5 (MYL5).	[12]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Myosin light chain 5 (MYL5).	[13]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl decreases the expression of Myosin light chain 5 (MYL5).	[13]
Methyl Mercury Ion	DM6YEW4	Investigative	Methyl Mercury Ion affects the expression of Myosin light chain 5 (MYL5).	[13]

References

• [1] The Bidirectional Regulation between MYL5 and HIF-1 Promotes Cervical Carcinoma Metastasis.Theranostics. 2017 Aug 23;7(15):3768-3780. doi: 10.7150/thno.20796. eCollection 2017.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [8] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [9] A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle. PLoS One. 2006 Dec 20;1(1):e97. doi: 10.1371/journal.pone.0000097.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [13] Inhibition of CXCL12-mediated chemotaxis of Jurkat cells by direct immunotoxicants. Arch Toxicol. 2016 Jul;90(7):1685-94. doi: 10.1007/s00204-015-1585-7. Epub 2015 Aug 28.