Details of Drug Off-Target (DOT)

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

• DOT Name: Myosin-binding protein H (MYBPH)
• Synonyms: MyBP-H; H-protein
• Gene Name: MYBPH
• Related Disease:
  Advanced cancer
  Depression
  Glioma
  Hepatocellular carcinoma
  Hypertrophic cardiomyopathy
  Hypospadias
  Lung squamous cell carcinoma
  Measles
  Neoplasm
  Nephropathy
  Systemic sclerosis
  Adult glioblastoma
  Glioblastoma multiforme
  Lung adenocarcinoma
  Amyotrophic lateral sclerosis
  Hereditary hemochromatosis
• UniProt ID: MYBPH_HUMAN
• Pfam ID: PF00041 ; PF07679
• Sequence:
  MMEKNTSEGPACSPEETASESAKVPTAEPPGEVAVSESTREEQVPKPQAPAPQAPTASTA
  TKPAPPSEDVPSAPLLLTLDDVSSSSVTVSWEPPERLGRLGLQGYVLELCREGASEWVPV
  SARPMMVTQQTVRNLALGDKFLLRVSAVSSAGAGPPAMLDQPIHIRENIEAPKIRVPRHL
  RQTYIRQVGETVNLQIPFQGKPKPQATWTHNGHALDSQRVSMRTGDQDSILFIRSAQRSD
  SGRYELTVRVEDLEAKAVIDILVIEKPGPPSSIRLLDVWGCNAALQWTPPQDTGNTELLG
  YMVQKADKKTGQWFTVLERYHPTTCTISDLIIGNSYSFRVFSENLCGLSTSATVTKELAH
  IQKADIAAKPKGFIERDFSEAPSFTQPLADHTSTPGYSTQLFCSVRASPKPKIIWMKNKM
  EIQGNPKYRALSEQGVCTLEIRKPSPFDSGVYTCKAINVLGEASVDCRLEVKASAAH
• Function: Binds to myosin; probably involved in interaction with thick myofilaments in the A-band.
• Tissue Specificity: Mainly expressed in the skeletal muscle. Slightly expressed in the left atrium and arteria mammaria interna.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Depression	DIS3XJ69	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[4]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Genetic Variation	[5]
Hypospadias	DIS48CCP	Strong	Biomarker	[6]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[7]
Measles	DISXSUID	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Nephropathy	DISXWP4P	Strong	Biomarker	[9]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[10]
Adult glioblastoma	DISVP4LU	moderate	Altered Expression	[11]
Glioblastoma multiforme	DISK8246	moderate	Altered Expression	[11]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[12]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[13]
Hereditary hemochromatosis	DISVG5MT	Limited	Biomarker	[14]

1 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 Myosin-binding protein H (MYBPH).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Myosin-binding protein H (MYBPH).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Myosin-binding protein H (MYBPH).	[17]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Myosin-binding protein H (MYBPH).	[18]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Myosin-binding protein H (MYBPH).	[19]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Myosin-binding protein H (MYBPH).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Myosin-binding protein H (MYBPH).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Myosin-binding protein H (MYBPH).	[22]

References

• [1] Protective immunity elicited by measles vaccine exerts anti-tumor effects on measles virus hemagglutinin gene-modified cancer cells in a mouse model.J Cancer Res Clin Oncol. 2018 Oct;144(10):1945-1957. doi: 10.1007/s00432-018-2720-7. Epub 2018 Aug 6.
• [2] Effect of amitriptyline treatment on neurofilament-H protein in an experimental model of depression.Brain Res Bull. 2017 Jan;128:1-6. doi: 10.1016/j.brainresbull.2016.11.001. Epub 2016 Nov 3.
• [3] Siglec-h on activated microglia for recognition and engulfment of glioma cells.Glia. 2013 Jul;61(7):1122-33. doi: 10.1002/glia.22501. Epub 2013 Apr 30.
• [4] Overexpression of CENP-H as a novel prognostic biomarker for human hepatocellular carcinoma progression and patient survival.Oncol Rep. 2013 Nov;30(5):2238-44. doi: 10.3892/or.2013.2675. Epub 2013 Aug 20.
• [5] MYBPH acts as modifier of cardiac hypertrophy in hypertrophic cardiomyopathy (HCM) patients.Hum Genet. 2016 May;135(5):477-483. doi: 10.1007/s00439-016-1649-7. Epub 2016 Mar 11.
• [6] Genome-wide DNA methylation profiling of CpG islands in hypospadias.J Urol. 2012 Oct;188(4 Suppl):1450-5. doi: 10.1016/j.juro.2012.03.047. Epub 2012 Aug 17.
• [7] Predicting the Lung Squamous Cell Carcinoma Diagnosis and Prognosis Markers by Unique DNA Methylation and Gene Expression Profiles.J Comput Biol. 2020 Jul;27(7):1041-1054. doi: 10.1089/cmb.2019.0138. Epub 2019 Nov 11.
• [8] KDELR2 Competes with Measles Virus Envelope Proteins for Cellular Chaperones Reducing Their Chaperone-Mediated Cell Surface Transport.Viruses. 2019 Jan 4;11(1):27. doi: 10.3390/v11010027.
• [9] Successful treatment with humanized anti-interleukin-6 receptor antibody (tocilizumab) in a case of AA amyloidosis complicated by familial Mediterranean fever.Mod Rheumatol. 2016 Jul;26(4):610-3. doi: 10.3109/14397595.2014.908810. Epub 2015 Jan 25.
• [10] Effects of selexipag and its active metabolite in contrasting the profibrotic myofibroblast activity in cultured scleroderma skin fibroblasts.Arthritis Res Ther. 2018 May 2;20(1):77. doi: 10.1186/s13075-018-1577-0.
• [11] Using Cystine Knot Proteins as a Novel Approach to Retarget Oncolytic Measles Virus.Mol Ther Oncolytics. 2017 Sep 29;7:57-66. doi: 10.1016/j.omto.2017.09.005. eCollection 2017 Dec 15.
• [12] MYBPH, a transcriptional target of TTF-1, inhibits ROCK1, and reduces cell motility and metastasis.EMBO J. 2012 Jan 18;31(2):481-93. doi: 10.1038/emboj.2011.416. Epub 2011 Nov 15.
• [13] Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients.Biochim Biophys Acta. 2014 Jan;1842(1):99-106. doi: 10.1016/j.bbadis.2013.10.013. Epub 2013 Oct 30.
• [14] Immunohistochemistry of HLA-H, the protein defective in patients with hereditary hemochromatosis, reveals unique pattern of expression in gastrointestinal tract.Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2534-9. doi: 10.1073/pnas.94.6.2534.
• [15] 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.
• [16] Retinoic acid-induced downmodulation of telomerase activity in human cancer cells. Exp Mol Pathol. 2005 Oct;79(2):108-17.
• [17] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [18] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [19] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [20] A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle. PLoS One. 2006 Dec 20;1(1):e97. doi: 10.1371/journal.pone.0000097.
• [21] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [22] Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014 May;13(5):1142-54.