Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWTRGT7)

• DOT Name: Myosin light chain 6B (MYL6B)
• Synonyms: Myosin light chain 1 slow-twitch muscle A isoform; MLC1sa; Smooth muscle and nonmuscle myosin light chain alkali 6B
• Gene Name: MYL6B
• Related Disease:
  Keloid
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: MYL6B_HUMAN
• PDB ID: 1OE9; 1W7I; 1W7J; 7PLT; 7PLU; 7PLV; 7PLW; 7PLX; 7PLY; 7PLZ; 7PM0; 7PM1; 7PM2; 7PM5; 7PM6; 7PM7; 7PM8; 7PM9; 7PMA; 7PMB; 7PMC; 7PMD; 7PME; 7PMF; 7PMG; 7PMH; 7PMI; 7PMJ; 7PML
• Sequence:
  MPPKKDVPVKKPAGPSISKPAAKPAAAGAPPAKTKAEPAVPQAPQKTQEPPVDLSKVVIE
  FNKDQLEEFKEAFELFDRVGDGKILYSQCGDVMRALGQNPTNAEVLKVLGNPKSDELKSR
  RVDFETFLPMLQAVAKNRGQGTYEDYLEGFRVFDKEGNGKVMGAELRHVLTTLGEKMTEE
  EVETVLAGHEDSNGCINYEAFLKHILSV
• Function: Regulatory light chain of myosin. Does not bind calcium.
• KEGG Pathway:
  Vascular smooth muscle contraction (hsa04270)
  Tight junction (hsa04530)
  Motor proteins (hsa04814)
  Oxytocin sig.ling pathway (hsa04921)
• Reactome Pathway: Smooth Muscle Contraction (R-HSA-445355)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Keloid	DISV09JY	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[2]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]

14 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 6B (MYL6B).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Myosin light chain 6B (MYL6B).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Myosin light chain 6B (MYL6B).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Myosin light chain 6B (MYL6B).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Myosin light chain 6B (MYL6B).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Myosin light chain 6B (MYL6B).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Myosin light chain 6B (MYL6B).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Myosin light chain 6B (MYL6B).	[9]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Myosin light chain 6B (MYL6B).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Myosin light chain 6B (MYL6B).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Myosin light chain 6B (MYL6B).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Myosin light chain 6B (MYL6B).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Myosin light chain 6B (MYL6B).	[16]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone affects the splicing of Myosin light chain 6B (MYL6B).	[17]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Myosin light chain 6B (MYL6B).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Myosin light chain 6B (MYL6B).	[13]

References

• [1] Comparative proteomic analysis between normal skin and keloid scar.Br J Dermatol. 2010 Jun;162(6):1302-15. doi: 10.1111/j.1365-2133.2010.09660.x. Epub 2010 Feb 1.
• [2] MYL6B, a myosin light chain, promotes MDM2-mediated p53 degradation and drives HCC development.J Exp Clin Cancer Res. 2018 Feb 13;37(1):28. doi: 10.1186/s13046-018-0693-7.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [10] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [13] 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.
• [14] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [15] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.