Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRN16R4)

• DOT Name: Myozenin-3 (MYOZ3)
• Synonyms: Calsarcin-3; FATZ-related protein 3
• Gene Name: MYOZ3
• Related Disease:
  Matthew-Wood syndrome
  Follicular lymphoma
• UniProt ID: MYOZ3_HUMAN
• Pfam ID: PF05556
• Sequence:
  MIPKEQKGPVMAAMGDLTEPVPTLDLGKKLSVPQDLMMEELSLRNNRGSLLFQKRQRRVQ
  KFTFELAASQRAMLAGSARRKVTGTAESGTVANANGPEGPNYRSELHIFPASPGASLGGP
  EGAHPAAAPAGCVPSPSALAPGYAEPLKGVPPEKFNHTAISKGYRCPWQEFVSYRDYQSD
  GRSHTPSPNDYRNFNKTPVPFGGPLVGGTFPRPGTPFIPEPLSGLELLRLRPSFNRVAQG
  WVRNLPESEEL
• Function: Myozenins may serve as intracellular binding proteins involved in linking Z line proteins such as alpha-actinin, gamma-filamin, TCAP/telethonin, LDB3/ZASP and localizing calcineurin signaling to the sarcomere. Plays an important role in the modulation of calcineurin signaling. May play a role in myofibrillogenesis.
• Tissue Specificity: Expressed specifically in skeletal muscle. Not detected in heart.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[1]
Follicular lymphoma	DISVEUR6	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Myozenin-3 (MYOZ3).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Myozenin-3 (MYOZ3).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Myozenin-3 (MYOZ3).	[4]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Myozenin-3 (MYOZ3).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Myozenin-3 (MYOZ3).	[6]
Fenfluramine	DM0762O	Phase 3	Fenfluramine decreases the expression of Myozenin-3 (MYOZ3).	[7]

References

• [1] Should platinum-based chemotherapy be preferred for germline BReast CAncer genes (BRCA) 1 and 2-mutated pancreatic ductal adenocarcinoma (PDAC) patients? A systematic review and meta-analysis.Cancer Treat Rev. 2019 Nov;80:101895. doi: 10.1016/j.ctrv.2019.101895. Epub 2019 Sep 6.
• [2] Follicular lymphoma frequently originates in the salivary gland.Pathol Int. 2006 Oct;56(10):576-83. doi: 10.1111/j.1440-1827.2006.02011.x.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [6] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [7] Fenfluramine-induced gene dysregulation in human pulmonary artery smooth muscle and endothelial cells. Pulm Circ. 2011 Jul-Sep;1(3):405-18. doi: 10.4103/2045-8932.87310.
• [8] 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.