Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8GGH11)

• DOT Name: Myomesin-3 (MYOM3)
• Synonyms: Myomesin family member 3
• Gene Name: MYOM3
• Related Disease:
  Cardiac failure
  Congestive heart failure
  Dilated cardiomyopathy 1A
• UniProt ID: MYOM3_HUMAN
• Pfam ID: PF00041 ; PF07679
• Sequence:
  MTLPHSLGGAGDPRPPQAMEVHRLEHRQEEEQKEERQHSLRMGSSVRRRTFRSSEEEHEF
  SAADYALAAALALTASSELSWEAQLRRQTSAVELEERGQKRVGFGNDWERTEIAFLQTHR
  LLRQRRDWKTLRRRTEEKVQEAKELRELCYGRGPWFWIPLRSHAVWEHTTVLLTCTVQAS
  PPPQVTWYKNDTRIDPRLFRAGKYRITNNYGLLSLEIRRCAIEDSATYTVRVKNAHGQAS
  SFAKVLVRTYLGKDAGFDSEIFKRSTFGPSVEFTSVLKPVFAREKEPFSLSCLFSEDVLD
  AESIQWFRDGSLLRSSRRRKILYTDRQASLKVSCTYKEDEGLYMVRVPSPFGPREQSTYV
  LVRDAEAENPGAPGSPLNVRCLDVNRDCLILTWAPPSDTRGNPITAYTIERCQGESGEWI
  ACHEAPGGTCRCPIQGLVEGQSYRFRVRAISRVGSSVPSKASELVVMGDHDAARRKTEIP
  FDLGNKITISTDAFEDTVTIPSPPTNVHASEIREAYVVLAWEEPSPRDRAPLTYSLEKSV
  IGSGTWEAISSESPVRSPRFAVLDLEKKKSYVFRVRAMNQYGLSDPSEPSEPIALRGPPA
  TLPPPAQVQAFRDTQTSVSLTWDPVKDPELLGYYIYSRKVGTSEWQTVNNKPIQGTRFTV
  PGLRTGKEYEFCVRSVSEAGVGESSAATEPIRVKQALATPSAPYGFALLNCGKNEMVIGW
  KPPKRRGGGKILGYFLDQHDSEELDWHAVNQQPIPTRVCKVSDLHEGHFYEFRARAANWA
  GVGELSAPSSLFECKEWTMPQPGPPYDVRASEVRATSLVLQWEPPLYMGAGPVTGYHVSF
  QEEGSEQWKPVTPGPISGTHLRVSDLQPGKSYVFQVQAMNSAGLGQPSMPTDPVLLEDKP
  GAHEIEVGVDEEGFIYLAFEAPEAPDSSEFQWSKDYKGPLDPQRVKIEDKVNKSKVILKE
  PGLEDLGTYSVIVTDADEDISASHTLTEEELEKLKKLSHEIRNPVIKLISGWNIDILERG
  EVRLWLEVEKLSPAAELHLIFNNKEIFSSPNRKINFDREKGLVEVIIQNLSEEDKGSYTA
  QLQDGKAKNQITLTLVDDDFDKLLRKADAKRRDWKRKQGPYFERPLQWKVTEDCQVQLTC
  KVTNTKKETRFQWFFQRAEMPDGQYDPETGTGLLCIEELSKKDKGIYRAMVSDDRGEDDT
  ILDLTGDALDAIFTELGRIGALSATPLKIQGTEEGIRIFSKVKYYNVEYMKTTWFHKDKR
  LESGDRIRTGTTLDEIWLHILDPKDSDKGKYTLEIAAGKEVRQLSTDLSGQAFEDAMAEH
  QRLKTLAIIEKNRAKVVRGLPDVATIMEDKTLCLTCIVSGDPTPEISWLKNDQPVTFLDR
  YRMEVRGTEVTITIEKVNSEDSGRYGVFVKNKYGSETGQVTISVFKHGDEPKELKSM
• Function: May link the intermediate filament cytoskeleton to the M-disk of the myofibrils in striated muscle.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Strong	Posttranslational Modification	[1]
Congestive heart failure	DIS32MEA	Strong	Posttranslational Modification	[1]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Myomesin-3 (MYOM3).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Myomesin-3 (MYOM3).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Myomesin-3 (MYOM3).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Myomesin-3 (MYOM3).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Myomesin-3 (MYOM3).	[5]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Myomesin-3 (MYOM3).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Myomesin-3 (MYOM3).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Myomesin-3 (MYOM3).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Myomesin-3 (MYOM3).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Myomesin-3 (MYOM3).	[11]

References

• [1] Targeted DNA Methylation Profiling of Human Cardiac Tissue Reveals Novel Epigenetic Traits and Gene Deregulation Across Different Heart Failure Patient Subtypes.Circ Heart Fail. 2019 Mar;12(3):e005765. doi: 10.1161/CIRCHEARTFAILURE.118.005765.
• [2] Rare genetic mutations in Pakistani patients with dilated cardiomyopathy.Gene. 2018 Oct 5;673:134-139. doi: 10.1016/j.gene.2018.06.019. Epub 2018 Jun 7.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] 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.