Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7ZNDP4)

• DOT Name: Myosin regulatory light chain 2, atrial isoform (MYL7)
• Synonyms: MLC-2a; MLC2a; Myosin light chain 2a; Myosin regulatory light chain 7
• Gene Name: MYL7
• Related Disease:
  Aortic valve stenosis
  Cardiac failure
  Congestive heart failure
  Megalencephalic leukoencephalopathy with subcortical cysts 2A
  Hypertrophic cardiomyopathy
  Megalencephalic leukoencephalopathy with subcortical cysts
• UniProt ID: MLRA_HUMAN
• Pfam ID: PF13202 ; PF13833
• Sequence:
  MASRKAGTRGKVAATKQAQRGSSNVFSMFEQAQIQEFKEAFSCIDQNRDGIICKADLRET
  YSQLGKVSVPEEELDAMLQEGKGPINFTVFLTLFGEKLNGTDPEEAILSAFRMFDPSGKG
  VVNKDEFKQLLLTQADKFSPAEVEQMFALTPMDLAGNIDYKSLCYIITHGDEKEE
• Tissue Specificity: Predominantly expressed in adult atrial muscle.
• KEGG Pathway:
  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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aortic valve stenosis	DISW7AQ9	Strong	Altered Expression	[1]
Cardiac failure	DISDC067	Strong	Biomarker	[1]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[1]
Megalencephalic leukoencephalopathy with subcortical cysts 2A	DISK3ULI	Strong	Genetic Variation	[2]
Hypertrophic cardiomyopathy	DISQG2AI	moderate	Altered Expression	[3]
Megalencephalic leukoencephalopathy with subcortical cysts	DISK9A1M	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Myosin regulatory light chain 2, atrial isoform (MYL7).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Myosin regulatory light chain 2, atrial isoform (MYL7).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Myosin regulatory light chain 2, atrial isoform (MYL7).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Myosin regulatory light chain 2, atrial isoform (MYL7).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Myosin regulatory light chain 2, atrial isoform (MYL7).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Myosin regulatory light chain 2, atrial isoform (MYL7).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Myosin regulatory light chain 2, atrial isoform (MYL7).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Myosin regulatory light chain 2, atrial isoform (MYL7).	[11]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Myosin regulatory light chain 2, atrial isoform (MYL7).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Myosin regulatory light chain 2, atrial isoform (MYL7).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ximelegatran	DMU8ANS	Approved	Ximelegatran decreases the phosphorylation of Myosin regulatory light chain 2, atrial isoform (MYL7).	[13]
Phenylephrine	DMZHUO5	Approved	Phenylephrine increases the phosphorylation of Myosin regulatory light chain 2, atrial isoform (MYL7).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Myosin regulatory light chain 2, atrial isoform (MYL7).	[14]
Wortmannin	DM8EVK5	Terminated	Wortmannin decreases the phosphorylation of Myosin regulatory light chain 2, atrial isoform (MYL7).	[13]

References

• [1] Induction by left ventricular overload and left ventricular failure of the human Jumonji gene (JARID2) encoding a protein that regulates transcription and reexpression of a protective fetal program.J Thorac Cardiovasc Surg. 2008 Sep;136(3):709-16. doi: 10.1016/j.jtcvs.2008.02.020. Epub 2008 Jun 9.
• [2] Identification in Chinese patients with GLIALCAM mutations of megalencephalic leukoencephalopathy with subcortical cysts and brain pathological study on Glialcam knock-in mouse models.World J Pediatr. 2019 Oct;15(5):454-464. doi: 10.1007/s12519-019-00284-w. Epub 2019 Aug 1.
• [3] Expression profiling of cardiac genes in human hypertrophic cardiomyopathy: insight into the pathogenesis of phenotypes.J Am Coll Cardiol. 2001 Oct;38(4):1175-80. doi: 10.1016/s0735-1097(01)01509-1.
• [4] Megalencephalic leukoencephalopathy with subcortical cysts: Characterization of disease variants.Neurology. 2018 Apr 17;90(16):e1395-e1403. doi: 10.1212/WNL.0000000000005334. Epub 2018 Mar 21.
• [5] 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.
• [6] Atrial-like Engineered Heart Tissue: An In?Vitro Model of the Human Atrium. Stem Cell Reports. 2018 Dec 11;11(6):1378-1390. doi: 10.1016/j.stemcr.2018.10.008. Epub 2018 Nov 8.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] Differentiation of human adipose-derived stem cells towards cardiomyocytes is facilitated by laminin. Cell Tissue Res. 2008 Dec;334(3):457-67. doi: 10.1007/s00441-008-0713-6. Epub 2008 Nov 7.
• [12] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [13] Key role of myosin light chain (MLC) kinase-mediated MLC2a phosphorylation in the alpha 1-adrenergic positive inotropic effect in human atrium. Cardiovasc Res. 2005 Jan 1;65(1):211-20. doi: 10.1016/j.cardiores.2004.09.019.
• [14] 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.
• [15] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.