Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD2UOXW)

• DOT Name: Myomesin-2 (MYOM2)
• Synonyms: 165 kDa connectin-associated protein; 165 kDa titin-associated protein; M-protein; Myomesin family member 2
• Gene Name: MYOM2
• Related Disease:
  Cardiac disease
  Hepatitis
  Hepatitis A virus infection
  Advanced cancer
  Age-related macular degeneration
  Alcoholic liver diseases
  Autoimmune disease
  Childhood myelodysplastic syndrome
  Chromosomal disorder
  Dengue
  Essential thrombocythemia
  Fatty liver disease
  Hepatitis B virus infection
  IgA nephropathy
  Influenza
  Measles
  Metastatic malignant neoplasm
  Myelodysplastic syndrome
  Myelofibrosis
  Non-alcoholic fatty liver disease
  Pharyngitis
  Plasma cell myeloma
  Plasma cell neoplasm
  Polycythemia vera
  Primary myelofibrosis
  Prostate neoplasm
  Psoriasis
  Psoriatic arthritis
  Rabies
  Rheumatic heart disease
  Severe acute respiratory syndrome (SARS)
  Streptococcus infection
  Waldenstrom macroglobulinemia
  Colon cancer
  Colon carcinoma
  Ankylosing spondylitis
  Chronic hepatitis B virus infection
  Ebola virus infection
  Non-alcoholic steatohepatitis
  Rheumatic fever
• UniProt ID: MYOM2_HUMAN
• Pfam ID: PF00041 ; PF07679
• Sequence:
  MSLVTVPFYQKRHRHFDQSYRNIQTRYLLDEYASKKRASTQASSQKSLSQRSSSQRASSQ
  TSLGGTICRVCAKRVSTQEDEEQENRSRYQSLVAAYGEAKRQRFLSELAHLEEDVHLARS
  QARDKLDKYAIQQMMEDKLAWERHTFEERISRAPEILVRLRSHTVWERMSVKLCFTVQGF
  PTPVVQWYKDGSLICQAAEPGKYRIESNYGVHTLEINRADFDDTATYSAVATNAHGQVST
  NAAVVVRRFRGDEEPFRSVGLPIGLPLSSMIPYTHFDVQFLEKFGVTFRREGETVTLKCT
  MLVTPDLKRVQPRAEWYRDDVLLKESKWTKMFFGEGQASLSFSHLHKDDEGLYTLRIVSR
  GGVSDHSAFLFVRDADPLVTGAPGAPMDLQCHDANRDYVIVTWKPPNTTTESPVMGYFVD
  RCEVGTNNWVQCNDAPVKICKYPVTGLFEGRSYIFRVRAVNSAGISRPSRVSDAVAALDP
  LDLRRLQAVHLEGEKEIAIYQDDLEGDAQVPGPPTGVHASEISRNYVVLSWEPPTPRGKD
  PLMYFIEKSVVGSGSWQRVNAQTAVRSPRYAVFDLMEGKSYVFRVLSANRHGLSEPSEIT
  SPIQAQDVTVVPSAPGRVLASRNTKTSVVVQWDRPKHEEDLLGYYVDCCVAGTNLWEPCN
  HKPIGYNRFVVHGLTTGEQYIFRVKAVNAVGMSENSQESDVIKVQAALTVPSHPYGITLL
  NCDGHSMTLGWKVPKFSGGSPILGYYLDKREVHHKNWHEVNSSPSKPTILTVDGLTEGSL
  YEFKIAAVNLAGIGEPSDPSEHFKCEAWTMPEPGPAYDLTFCEVRDTSLVMLWKAPVYSG
  SSPVSGYFVDFREEDAGEWITVNQTTTASRYLKVSDLQQGKTYVFRVRAVNANGVGKPSD
  TSEPVLVEARPGTKEISAGVDEQGNIYLGFDCQEMTDASQFTWCKSYEEISDDERFKIET
  VGDHSKLYLKNPDKEDLGTYSVSVSDTDGVSSSFVLDPEELERLMALSNEIKNPTIPLKS
  ELAYEIFDKGRVRFWLQAEHLSPDASYRFIINDREVSDSEIHRIKCDKATGIIEMVMDRF
  SIENEGTYTVQIHDGKAKSQSSLVLIGDAFKTVLEEAEFQRKEFLRKQGPHFAEYLHWDV
  TEECEVRLVCKVANTKKETVFKWLKDDVLYETETLPNLERGICELLIPKLSKKDHGEYKA
  TLKDDRGQDVSILEIAGKVYDDMILAMSRVCGKSASPLKVLCTPEGIRLQCFMKYFTDEM
  KVNWCHKDAKISSSEHMRIGGSEEMAWLQICEPTEKDKGKYTFEIFDGKDNHQRSLDLSG
  QAFDEAFAEFQQFKAAAFAEKNRGRLIGGLPDVVTIMEGKTLNLTCTVFGNPDPEVIWFK
  NDQDIQLSEHFSVKVEQAKYVSMTIKGVTSEDSGKYSINIKNKYGGEKIDVTVSVYKHGE
  KIPDMAPPQQAKPKLIPASASAAGQ
• Function: Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac disease	DISVO1I5	Definitive	Biomarker	[1]
Hepatitis	DISXXX35	Definitive	Biomarker	[2]
Hepatitis A virus infection	DISUMFQV	Definitive	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[4]
Alcoholic liver diseases	DISXEPHQ	Strong	Genetic Variation	[5]
Autoimmune disease	DISORMTM	Strong	Biomarker	[6]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Biomarker	[7]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[8]
Dengue	DISKH221	Strong	Biomarker	[9]
Essential thrombocythemia	DISWWK11	Strong	Biomarker	[7]
Fatty liver disease	DIS485QZ	Strong	Genetic Variation	[5]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[10]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[11]
Influenza	DIS3PNU3	Strong	Biomarker	[12]
Measles	DISXSUID	Strong	Genetic Variation	[13]
Metastatic malignant neoplasm	DIS86UK6	Strong	Genetic Variation	[14]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[7]
Myelofibrosis	DISIMP21	Strong	Biomarker	[7]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Genetic Variation	[5]
Pharyngitis	DISSN548	Strong	Biomarker	[15]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[16]
Plasma cell neoplasm	DIS2PJJM	Strong	Biomarker	[17]
Polycythemia vera	DISB5FPO	Strong	Biomarker	[7]
Primary myelofibrosis	DIS6L0CN	Strong	Biomarker	[7]
Prostate neoplasm	DISHDKGQ	Strong	Genetic Variation	[18]
Psoriasis	DIS59VMN	Strong	Biomarker	[19]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[20]
Rabies	DISSC4V5	Strong	Biomarker	[21]
Rheumatic heart disease	DISCI8JQ	Strong	Biomarker	[22]
Severe acute respiratory syndrome (SARS)	DISYW14W	Strong	Biomarker	[23]
Streptococcus infection	DIS04U9T	Strong	Biomarker	[24]
Waldenstrom macroglobulinemia	DIS9O23I	Strong	Biomarker	[25]
Colon cancer	DISVC52G	moderate	Genetic Variation	[26]
Colon carcinoma	DISJYKUO	moderate	Genetic Variation	[26]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[27]
Chronic hepatitis B virus infection	DISHL4NT	Limited	Biomarker	[28]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[29]
Non-alcoholic steatohepatitis	DIST4788	Limited	Biomarker	[30]
Rheumatic fever	DISLUF66	Limited	Biomarker	[31]

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-2 (MYOM2).	[32]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Myomesin-2 (MYOM2).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Myomesin-2 (MYOM2).	[34]

9 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-2 (MYOM2).	[33]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Myomesin-2 (MYOM2).	[35]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone decreases the expression of Myomesin-2 (MYOM2).	[33]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Myomesin-2 (MYOM2).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Myomesin-2 (MYOM2).	[36]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Myomesin-2 (MYOM2).	[37]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Myomesin-2 (MYOM2).	[38]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Myomesin-2 (MYOM2).	[39]
Choline	DM5D9YK	Investigative	Choline affects the expression of Myomesin-2 (MYOM2).	[40]

References

• [1] Induction of autoimmune valvular heart disease by recombinant streptococcal m protein.Infect Immun. 2001 Jun;69(6):4072-8. doi: 10.1128/IAI.69.6.4072-4078.2001.
• [2] The cytoplasmic tail of mouse hepatitis virus M protein is essential but not sufficient for its retention in the Golgi complex.J Biol Chem. 1994 Nov 11;269(45):28263-9.
• [3] Laboratory testing for monoclonal gammopathies: Focus on monoclonal gammopathy of undetermined significance and smoldering multiple myeloma.Clin Biochem. 2018 Jan;51:38-47. doi: 10.1016/j.clinbiochem.2017.05.001. Epub 2017 May 4.
• [4] Complement factor H allotype 402H is associated with increased C3b opsonization and phagocytosis of Streptococcus pyogenes.Mol Microbiol. 2008 Nov;70(3):583-94. doi: 10.1111/j.1365-2958.2008.06347.x. Epub 2008 Jun 27.
• [5] Effect of PNPLA3 rs738409 variant (I148 M) on hepatic steatosis, necroinflammation, and fibrosis in Japanese patients with chronic hepatitis C.J Gastroenterol. 2015 Aug;50(8):887-93. doi: 10.1007/s00535-014-1018-z. Epub 2014 Nov 26.
• [6] Clinical and microbiological response of mice to intranasal inoculation with Lactococcus lactis expressing Group A Streptococcus antigens, to be used as an anti-streptococcal vaccine.Microbiol Immunol. 2018 Nov;62(11):711-719. doi: 10.1111/1348-0421.12657.
• [7] The presence of monoclonal gammopathy in Ph-negative myeloproliferative neoplasms is associated with a detrimental effect on outcomes.Leuk Lymphoma. 2017 Nov;58(11):2582-2587. doi: 10.1080/10428194.2017.1312380. Epub 2017 May 9.
• [8] Chronic neutrophilic leukemia associated with chronic lymphocytic leukemia.Int J Hematol. 1998 Jul;68(1):87-94. doi: 10.1016/s0925-5710(98)00031-0.
• [9] Dengue Virus M Protein Promotes NLRP3 Inflammasome Activation To Induce Vascular Leakage in Mice.J Virol. 2019 Oct 15;93(21):e00996-19. doi: 10.1128/JVI.00996-19. Print 2019 Nov 1.
• [10] Hypermodification and immune escape of an internally deleted middle-envelope (M) protein of frequent and predominant hepatitis B virus variants.Virology. 2002 Jan 5;292(1):44-58. doi: 10.1006/viro.2001.1239.
• [11] Streptococcal M protein enhances TGF-beta production and increases surface IgA-positive B cells in vitro in IgA nephropathy.Nephrol Dial Transplant. 2000 Jun;15(6):772-7. doi: 10.1093/ndt/15.6.772.
• [12] Binding host proteins to the M protein contributes to the mortality associated with influenza-Streptococcus pyogenes superinfections.Microbiology (Reading). 2017 Oct;163(10):1445-1456. doi: 10.1099/mic.0.000532.
• [13] Molecular characterization of measles virus strains causing subacute sclerosing panencephalitis in France in 1977 and 2007.J Med Virol. 2011 Sep;83(9):1614-23. doi: 10.1002/jmv.22152.
• [14] Systemic therapy of experimental breast cancer metastases by mutant vesicular stomatitis virus in immune-competent mice.Cancer Gene Ther. 2005 Apr;12(4):350-8. doi: 10.1038/sj.cgt.7700794.
• [15] Concerns for efficacy of a 30-valent M-protein-based Streptococcus pyogenes vaccine in regions with high rates of rheumatic heart disease.PLoS Negl Trop Dis. 2019 Jul 3;13(7):e0007511. doi: 10.1371/journal.pntd.0007511. eCollection 2019 Jul.
• [16] Therapeutic Advances in the Management of Smoldering Myeloma.Am J Ther. 2020 Mar/Apr;27(2):e194-e203. doi: 10.1097/MJT.0000000000001034.
• [17] POEMS Syndrome: 2019 Update on diagnosis, risk-stratification, and management.Am J Hematol. 2019 Jul;94(7):812-827. doi: 10.1002/ajh.25495. Epub 2019 May 23.
• [18] Sensitivity of prostate tumors to wild type and M protein mutant vesicular stomatitis viruses.Virology. 2004 Dec 5;330(1):34-49. doi: 10.1016/j.virol.2004.08.039.
• [19] Non-M protein(s) on the cell wall and membrane of group A streptococci induce(s) IFN-gamma production by dermal CD4+ T cells in psoriasis.Arch Dermatol Res. 2001 Apr;293(4):165-70. doi: 10.1007/s004030100218.
• [20] Significance of antibodies to streptococcal M protein in psoriatic arthritis and their association with HLA-A*0207.Tissue Antigens. 1996 Dec;48(6):645-50. doi: 10.1111/j.1399-0039.1996.tb02687.x.
• [21] Generation of Monoclonal Antibodies against Variable Epitopes of the M Protein of Rabies Virus.Viruses. 2019 Apr 23;11(4):375. doi: 10.3390/v11040375.
• [22] Interleukin-10: Role in increasing susceptibility and pathogenesis of rheumatic fever/rheumatic heart disease.Cytokine. 2017 Feb;90:169-176. doi: 10.1016/j.cyto.2016.11.010. Epub 2016 Dec 3.
• [23] Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain.Cell Mol Immunol. 2014 Mar;11(2):141-9. doi: 10.1038/cmi.2013.61. Epub 2014 Feb 10.
• [24] Safety and immunogenicity of a 30-valent M protein-based group a streptococcal vaccine in healthy adult volunteers: A randomized, controlled phase I study.Vaccine. 2020 Feb 5;38(6):1384-1392. doi: 10.1016/j.vaccine.2019.12.005. Epub 2019 Dec 13.
• [25] Kidney diseases associated with Waldenstrm macroglobulinemia.Nephrol Dial Transplant. 2019 Oct 1;34(10):1644-1652. doi: 10.1093/ndt/gfy320.
• [26] Immune Effects of M51R Vesicular Stomatitis Virus Treatment of Carcinomatosis From Colon Cancer.J Surg Res. 2020 Jan;245:127-135. doi: 10.1016/j.jss.2019.07.032. Epub 2019 Aug 12.
• [27] IgG Galactosylation status combined with MYOM2-rs2294066 precisely predicts anti-TNF response in ankylosing spondylitis.Mol Med. 2019 Jun 13;25(1):25. doi: 10.1186/s10020-019-0093-2.
• [28] Extraction and purification of hepatitis B virus-like M particles from a recombinant Saccharomyces cerevisiae strain using alumina powder.J Virol Methods. 2013 Jan;187(1):132-7. doi: 10.1016/j.jviromet.2012.09.023. Epub 2012 Oct 8.
• [29] Functional characterization of Ebola virus L-domains using VSV recombinants.Virology. 2005 Jun 5;336(2):291-8. doi: 10.1016/j.virol.2005.03.027.
• [30] Protein kinase MST3 modulates lipid homeostasis in hepatocytes and correlates with nonalcoholic steatohepatitis in humans.FASEB J. 2019 Sep;33(9):9974-9989. doi: 10.1096/fj.201900356RR. Epub 2019 Jun 7.
• [31] Systems immunology reveals a linked IgG3-C4 response in patients with acute rheumatic fever.Immunol Cell Biol. 2020 Jan;98(1):12-21. doi: 10.1111/imcb.12298. Epub 2019 Nov 18.
• [32] 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.
• [33] Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment. Arch Toxicol. 2016 Nov;90(11):2763-2777.
• [34] 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.
• [35] Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells. Arch Toxicol. 2018 Apr;92(4):1507-1524.
• [36] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [37] 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.
• [38] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [39] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [40] Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not. Am J Clin Nutr. 2007 Jul;86(1):230-9. doi: 10.1093/ajcn/86.1.230.