Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCXSB6A)

• DOT Name: Myosin-binding protein C, fast-type (MYBPC2)
• Synonyms: Fast MyBP-C; C-protein, skeletal muscle fast isoform
• Gene Name: MYBPC2
• Related Disease:
  Cardiomyopathy
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Familial hypertrophic cardiomyopathy
  Myopathy
  Hypertrophic cardiomyopathy
• UniProt ID: MYPC2_HUMAN
• PDB ID: 2E7C; 2EDK; 2EDN
• Pfam ID: PF00041 ; PF07679 ; PF18362
• Sequence:
  MPEAKPAAKKAPKGKDAPKGAPKEAPPKEAPAEAPKEAPPEDQSPTAEEPTGVFLKKPDS
  VSVETGKDAVVVAKVNGKELPDKPTIKWFKGKWLELGSKSGARFSFKESHNSASNVYTVE
  LHIGKVVLGDRGYYRLEVKAKDTCDSCGFNIDVEAPRQDASGQSLESFKRTSEKKSDTAG
  ELDFSGLLKKREVVEEEKKKKKKDDDDLGIPPEIWELLKGAKKSEYEKIAFQYGITDLRG
  MLKRLKKAKVEVKKSAAFTKKLDPAYQVDRGNKIKLMVEISDPDLTLKWFKNGQEIKPSS
  KYVFENVGKKRILTINKCTLADDAAYEVAVKDEKCFTELFVKEPPVLIVTPLEDQQVFVG
  DRVEMAVEVSEEGAQVMWMKDGVELTREDSFKARYRFKKDGKRHILIFSDVVQEDRGRYQ
  VITNGGQCEAELIVEEKQLEVLQDIADLTVKASEQAVFKCEVSDEKVTGKWYKNGVEVRP
  SKRITISHVGRFHKLVIDDVRPEDEGDYTFVPDGYALSLSAKLNFLEIKVEYVPKQEPPK
  IHLDCSGKTSENAIVVVAGNKLRLDVSITGEPPPVATWLKGDEVFTTTEGRTRIEKRVDC
  SSFVIESAQREDEGRYTIKVTNPVGEDVASIFLQVVDVPDPPEAVRITSVGEDWAILVWE
  PPMYDGGKPVTGYLVERKKKGSQRWMKLNFEVFTETTYESTKMIEGILYEMRVFAVNAIG
  VSQPSMNTKPFMPIAPTSEPLHLIVEDVTDTTTTLKWRPPNRIGAGGIDGYLVEYCLEGS
  EEWVPANTEPVERCGFTVKNLPTGARILFRVVGVNIAGRSEPATLAQPVTIREIAEPPKI
  RLPRHLRQTYIRKVGEQLNLVVPFQGKPRPQVVWTKGGAPLDTSRVHVRTSDFDTVFFVR
  QAARSDSGEYELSVQIENMKDTATIRIRVVEKAGPPINVMVKEVWGTNALVEWQAPKDDG
  NSEIMGYFVQKADKKTMEWFNVYERNRHTSCTVSDLIVGNEYYFRVYTENICGLSDSPGV
  SKNTARILKTGITFKPFEYKEHDFRMAPKFLTPLIDRVVVAGYSAALNCAVRGHPKPKVV
  WMKNKMEIREDPKFLITNYQGVLTLNIRRPSPFDAGTYTCRAVNELGEALAECKLEVRVP
  Q
• Function: Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway: Striated Muscle Contraction (R-HSA-390522)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[1]
Dilated cardiomyopathy	DISX608J	Strong	Genetic Variation	[2]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[2]
Familial hypertrophic cardiomyopathy	DISQ89HN	Strong	Genetic Variation	[3]
Myopathy	DISOWG27	Strong	Biomarker	[1]
Hypertrophic cardiomyopathy	DISQG2AI	moderate	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Myosin-binding protein C, fast-type (MYBPC2).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Myosin-binding protein C, fast-type (MYBPC2).	[6]

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 increases the methylation of Myosin-binding protein C, fast-type (MYBPC2).	[7]

References

• [1] Myosin binding protein C: implications for signal-transduction.J Muscle Res Cell Motil. 2012 May;33(1):31-42. doi: 10.1007/s10974-011-9281-6. Epub 2011 Dec 16.
• [2] A frameshift deletion mutation in the cardiac myosin-binding protein C gene associated with dilated phase of hypertrophic cardiomyopathy and dilated cardiomyopathy.J Cardiol. 2010 Sep;56(2):189-96. doi: 10.1016/j.jjcc.2010.04.003. Epub 2010 Jun 4.
• [3] Relation between QT duration and maximal wall thickness in familial hypertrophic cardiomyopathy.Heart. 2002 Aug;88(2):153-7. doi: 10.1136/heart.88.2.153.
• [4] Lifelong left ventricular remodeling of hypertrophic cardiomyopathy caused by a founder frameshift deletion mutation in the cardiac Myosin-binding protein C gene among Japanese.J Am Coll Cardiol. 2005 Nov 1;46(9):1737-43. doi: 10.1016/j.jacc.2005.05.087. Epub 2005 Oct 10.
• [5] 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.
• [6] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [7] 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.