Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTVO2S5)

• DOT Name: Myogenic factor 5 (MYF5)
• Synonyms: Myf-5; Class C basic helix-loop-helix protein 2; bHLHc2
• Gene Name: MYF5
• Related Disease:
  Non-insulin dependent diabetes
  Cleft palate
  Congenital fibrosis of extraocular muscles
  Isolated cleft palate
  Neoplasm
  Ophthalmoplegia, external, with rib and vertebral anomalies
  Rhabdomyosarcoma
  Advanced cancer
  facioscapulohumeral muscular dystrophy
  Malignant rhabdoid tumour
• UniProt ID: MYF5_HUMAN
• PDB ID: 7Z5I; 7Z5K
• Pfam ID: PF01586 ; PF00010 ; PF12232
• Sequence:
  MDVMDGCQFSPSEYFYDGSCIPSPEGEFGDEFVPRVAAFGAHKAELQGSDEDEHVRAPTG
  HHQAGHCLMWACKACKRKSTTMDRRKAATMRERRRLKKVNQAFETLKRCTTTNPNQRLPK
  VEILRNAIRYIESLQELLREQVENYYSLPGQSCSEPTSPTSNCSDGMPECNSPVWSRKSS
  TFDSIYCPDVSNVYATDKNSLSSLDCLSNIVDRITSSEQPGLPLQDLASLSPVASTDSQP
  ATPGASSSRLIYHVL
• Function: Transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation. Together with MYOG and MYOD1, co-occupies muscle-specific gene promoter core region during myogenesis. Induces fibroblasts to differentiate into myoblasts. Probable sequence specific DNA-binding protein.
• KEGG Pathway: Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
• Reactome Pathway: Myogenesis (R-HSA-525793)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Altered Expression	[1]
Cleft palate	DIS6G5TF	Strong	Biomarker	[2]
Congenital fibrosis of extraocular muscles	DISE84PU	Strong	Genetic Variation	[3]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Ophthalmoplegia, external, with rib and vertebral anomalies	DIS24B5C	Strong	Autosomal recessive	[5]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[4]
Advanced cancer	DISAT1Z9	Limited	Genetic Variation	[6]
facioscapulohumeral muscular dystrophy	DISSE0H0	Limited	Altered Expression	[7]
Malignant rhabdoid tumour	DIS46HZU	Limited	Biomarker	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Myogenic factor 5 (MYF5).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Myogenic factor 5 (MYF5).	[10]
Amiloride	DMRTSGP	Approved	Amiloride increases the expression of Myogenic factor 5 (MYF5).	[11]

2 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 affects the methylation of Myogenic factor 5 (MYF5).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Myogenic factor 5 (MYF5).	[13]

References

• [1] Mild hyperbaric oxygen inhibits the growth-related decline in skeletal muscle oxidative capacity and prevents hyperglycemia in rats with type 2 diabetes mellitus.J Diabetes. 2018 Sep;10(9):753-763. doi: 10.1111/1753-0407.12666. Epub 2018 May 17.
• [2] Altered binding of MYF-5 to FOXE1 promoter in non-syndromic and CHARGE-associated cleft palate.J Oral Pathol Med. 2009 Jan;38(1):18-23. doi: 10.1111/j.1600-0714.2008.00726.x.
• [3] Recessive MYF5 Mutations Cause External Ophthalmoplegia, Rib, and Vertebral Anomalies.Am J Hum Genet. 2018 Jul 5;103(1):115-124. doi: 10.1016/j.ajhg.2018.05.003. Epub 2018 Jun 7.
• [4] Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma.Elife. 2017 Jan 12;6:e19214. doi: 10.7554/eLife.19214.
• [5] Distinct regulatory cascades govern extraocular and pharyngeal arch muscle progenitor cell fates. Dev Cell. 2009 Jun;16(6):810-21. doi: 10.1016/j.devcel.2009.05.008.
• [6] The Hippo effector TAZ (WWTR1) transforms myoblasts and TAZ abundance is associated with reduced survival in embryonal rhabdomyosarcoma.J Pathol. 2016 Sep;240(1):3-14. doi: 10.1002/path.4745.
• [7] DUX4c is up-regulated in FSHD. It induces the MYF5 protein and human myoblast proliferation.PLoS One. 2009 Oct 15;4(10):e7482. doi: 10.1371/journal.pone.0007482.
• [8] Expression of pericyte, mesangium and muscle markers in malignant rhabdoid tumor cell lines: differentiation-induction using 5-azacytidine.Cancer Sci. 2003 Dec;94(12):1059-65. doi: 10.1111/j.1349-7006.2003.tb01401.x.
• [9] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [10] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [11] In vivo and in vitro dysferlin expression in human muscle satellite cells. J Neuropathol Exp Neurol. 2004 Oct;63(10):1104-13. doi: 10.1093/jnen/63.10.1104.
• [12] 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.
• [13] Bisphenol A Represses Dopaminergic Neuron Differentiation from Human Embryonic Stem Cells through Downregulating the Expression of Insulin-like Growth Factor 1. Mol Neurobiol. 2017 Jul;54(5):3798-3812. doi: 10.1007/s12035-016-9898-y. Epub 2016 Jun 7.