Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8YBDOT)

• DOT Name: Myosin-1 (MYH1)
• Synonyms: Myosin heavy chain 1; Myosin heavy chain 2x; MyHC-2x; Myosin heavy chain IIx/d; MyHC-IIx/d; Myosin heavy chain, skeletal muscle, adult 1
• Gene Name: MYH1
• Related Disease:
  Autoimmune disease
  Focal segmental glomerulosclerosis
  Myositis disease
  Vitamin D deficiency
  Deafness dystonia syndrome
  Muir-Torre syndrome
• UniProt ID: MYH1_HUMAN
• Pfam ID: PF00063 ; PF02736 ; PF01576
• Sequence:
  MSSDSEMAIFGEAAPFLRKSERERIEAQNKPFDAKTSVFVVDPKESFVKATVQSREGGKV
  TAKTEAGATVTVKDDQVFPMNPPKYDKIEDMAMMTHLHEPAVLYNLKERYAAWMIYTYSG
  LFCVTVNPYKWLPVYNAEVVTAYRGKKRQEAPPHIFSISDNAYQFMLTDRENQSILITGE
  SGAGKTVNTKRVIQYFATIAVTGEKKKEEVTSGKMQGTLEDQIISANPLLEAFGNAKTVR
  NDNSSRFGKFIRIHFGTTGKLASADIETYLLEKSRVTFQLKAERSYHIFYQIMSNKKPDL
  IEMLLITTNPYDYAFVSQGEITVPSIDDQEELMATDSAIEILGFTSDERVSIYKLTGAVM
  HYGNMKFKQKQREEQAEPDGTEVADKAAYLQNLNSADLLKALCYPRVKVGNEYVTKGQTV
  QQVYNAVGALAKAVYDKMFLWMVTRINQQLDTKQPRQYFIGVLDIAGFEIFDFNSLEQLC
  INFTNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLAACIELIEKPMGIFSILEEE
  CMFPKATDTSFKNKLYEQHLGKSNNFQKPKPAKGKPEAHFSLIHYAGTVDYNIAGWLDKN
  KDPLNETVVGLYQKSAMKTLALLFVGATGAEAEAGGGKKGGKKKGSSFQTVSALFRENLN
  KLMTNLRSTHPHFVRCIIPNETKTPGAMEHELVLHQLRCNGVLEGIRICRKGFPSRILYA
  DFKQRYKVLNASAIPEGQFIDSKKASEKLLGSIDIDHTQYKFGHTKVFFKAGLLGLLEEM
  RDEKLAQLITRTQAMCRGFLARVEYQKMVERRESIFCIQYNVRAFMNVKHWPWMKLYFKI
  KPLLKSAETEKEMANMKEEFEKTKEELAKTEAKRKELEEKMVTLMQEKNDLQLQVQAEAD
  SLADAEERCDQLIKTKIQLEAKIKEVTERAEDEEEINAELTAKKRKLEDECSELKKDIDD
  LELTLAKVEKEKHATENKVKNLTEEMAGLDETIAKLTKEKKALQEAHQQTLDDLQAEEDK
  VNTLTKAKIKLEQQVDDLEGSLEQEKKIRMDLERAKRKLEGDLKLAQESTMDIENDKQQL
  DEKLKKKEFEMSGLQSKIEDEQALGMQLQKKIKELQARIEELEEEIEAERASRAKAEKQR
  SDLSRELEEISERLEEAGGATSAQIEMNKKREAEFQKMRRDLEEATLQHEATAATLRKKH
  ADSVAELGEQIDNLQRVKQKLEKEKSEMKMEIDDLASNMETVSKAKGNLEKMCRALEDQL
  SEIKTKEEEQQRLINDLTAQRARLQTESGEYSRQLDEKDTLVSQLSRGKQAFTQQIEELK
  RQLEEEIKAKSALAHALQSSRHDCDLLREQYEEEQEAKAELQRAMSKANSEVAQWRTKYE
  TDAIQRTEELEEAKKKLAQRLQDAEEHVEAVNAKCASLEKTKQRLQNEVEDLMIDVERTN
  AACAALDKKQRNFDKILAEWKQKCEETHAELEASQKESRSLSTELFKIKNAYEESLDQLE
  TLKRENKNLQQEISDLTEQIAEGGKRIHELEKIKKQVEQEKSELQAALEEAEASLEHEEG
  KILRIQLELNQVKSEVDRKIAEKDEEIDQMKRNHIRIVESMQSTLDAEIRSRNDAIRLKK
  KMEGDLNEMEIQLNHANRMAAEALRNYRNTQAILKDTQLHLDDALRSQEDLKEQLAMVER
  RANLLQAEIEELRATLEQTERSRKIAEQELLDASERVQLLHTQNTSLINTKKKLETDISQ
  IQGEMEDIIQEARNAEEKAKKAITDAAMMAEELKKEQDTSAHLERMKKNLEQTVKDLQHR
  LDEAEQLALKGGKKQIQKLEARVRELEGEVESEQKRNVEAVKGLRKHERKVKELTYQTEE
  DRKNILRLQDLVDKLQAKVKSYKRQAEEAEEQSNVNLSKFRRIQHELEEAEERADIAESQ
  VNKLRVKSREVHTKIISEE
• Function: Muscle contraction.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Cytoskeleton in muscle cells (hsa04820)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[1]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Genetic Variation	[2]
Myositis disease	DISCIXF0	Strong	Genetic Variation	[1]
Vitamin D deficiency	DISAWKYI	Strong	Altered Expression	[3]
Deafness dystonia syndrome	DIS0480U	Limited	Genetic Variation	[4]
Muir-Torre syndrome	DISKFFSW	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Myosin-1 (MYH1).	[5]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Myosin-1 (MYH1).	[6]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Myosin-1 (MYH1).	[7]

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 affects the methylation of Myosin-1 (MYH1).	[8]

References

• [1] A missense mutation in MYH1 is associated with susceptibility to immune-mediated myositis in Quarter Horses.Skelet Muscle. 2018 Mar 6;8(1):7. doi: 10.1186/s13395-018-0155-0.
• [2] Effects of FSGS-associated mutations on the stability and function of myosin-1 in fission yeast.Dis Model Mech. 2015 Aug 1;8(8):891-902. doi: 10.1242/dmm.020214. Epub 2015 Jun 18.
• [3] Disrupted expression of genes essential for skeletal muscle fibre integrity and energy metabolism in Vitamin D deficient rats.J Steroid Biochem Mol Biol. 2020 Mar;197:105525. doi: 10.1016/j.jsbmb.2019.105525. Epub 2019 Nov 6.
• [4] An individual with Muir-Torre syndrome found to have a pathogenic MSH6 gene mutation.Fam Cancer. 2007;6(3):317-21. doi: 10.1007/s10689-007-9119-y. Epub 2007 Feb 24.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [7] 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.
• [8] 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.