Details of Drug Off-Target (DOT)

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

• DOT Name: Unconventional myosin-Vc (MYO5C)
• Gene Name: MYO5C
• Related Disease:
  Drug dependence
  Substance abuse
  Substance dependence
  Diabetic retinopathy
  Retinopathy
  Alzheimer disease
  Lewy body dementia
  Parkinson disease
• UniProt ID: MYO5C_HUMAN
• PDB ID: 4L8T; 4ZG4; 5HMP
• Pfam ID: PF01843 ; PF00612 ; PF00063
• Sequence:
  MAVAELYTQYNRVWIPDPEEVWKSAEIAKDYRVGDKVLRLLLEDGTELDYSVNPESLPPL
  RNPDILVGENDLTALSYLHEPAVLHNLRIRFAESKLIYTYSGIILVAMNPYKQLPIYGDA
  IIHAYSGQNMGDMDPHIFAVAEEAYKQMARNNRNQSIIVSGESGAGKTVSARYAMRYFAT
  VSKSGSNAHVEDKVLASNPITEAVGNAKTTRNDNSSRFGKYTEISFDEQNQIIGANMSTY
  LLEKSRVVFQSENERNYHIFYQLCASAQQSEFKHLKLGSAEEFNYTRMGGNTVIEGVNDR
  AEMVETQKTFTLLGFKEDFQMDVFKILAAILHLGNVQITAVGNERSSVSEDDSHLKVFCE
  LLGLESGRVAQWLCNRKIVTSSETVVKPMTRPQAVNARDALAKKIYAHLFDFIVERINQA
  LQFSGKQHTFIGVLDIYGFETFDVNSFEQFCINYANEKLQQQFNMHVFKLEQEEYMKEDI
  PWTLIDFYDNQPVIDLIEAKMGILELLDEECLLPHGTDENWLQKLYNNFVNRNPLFEKPR
  MSNTSFVIQHFADKVEYKCEGFLEKNRDTVYDMLVEILRASKFHLCANFFQENPTPPSPF
  GSMITVKSAKQVIKPNSKHFRTTVGSKFRSSLYLLMETLNATTPHYVRCIKPNDEKLPFE
  FDSKRIVQQLRACGVLETIRISAQSYPSRWTYIEFYSRYGILMTKQELSFSDKKEVCKVV
  LHRLIQDSNQYQFGKTKIFFRAGQVAYLEKLRLDKLRQSCVMVQKHMRGWLQRKKFLRER
  RAALIIQQYFRGQQTVRKAITAVALKEAWAAIIIQKHCRGYLVRSLYQLIRMATITMQAY
  SRGFLARRRYRKMLEEHKAVILQKYARAWLARRRFQSIRRFVLNIQLTYRVQRLQKKLED
  QNKENHGLVEKLTSLAALRAGDVEKIQKLEAELEKAATHRRNYEEKGKRYRDAVEEKLAK
  LQKHNSELETQKEQIQLKLQEKTEELKEKMDNLTKQLFDDVQKEERQRMLLEKSFELKTQ
  DYEKQIQSLKEEIKALKDEKMQLQHLVEGEHVTSDGLKAEVARLSKQVKTISEFEKEIEL
  LQAQKIDVEKHVQSQKREMREKMSEITKQLLESYDIEDVRSRLSVEDLEHLNEDGELWFA
  YEGLKKATRVLESHFQSQKDCYEKEIEALNFKVVHLSQEINHLQKLFREENDINESIRHE
  VTRLTSENMMIPDFKQQISELEKQKQDLEIRLNEQAEKMKGKLEELSNQLHRSQEEEGTQ
  RKALEAQNEIHTKEKEKLIDKIQEMQEASDHLKKQFETESEVKCNFRQEASRLTLENRDL
  EEELDMKDRVIKKLQDQVKTLSKTIGKANDVHSSSGPKEYLGMLQYKREDEAKLIQNLIL
  DLKPRGVVVNMIPGLPAHILFMCVRYADSLNDANMLKSLMNSTINGIKQVVKEHLEDFEM
  LSFWLSNTCHFLNCLKQYSGEEEFMKHNSPQQNKNCLNNFDLSEYRQILSDVAIRIYHQF
  IIIMEKNIQPIIVPGMLEYESLQGISGLKPTGFRKRSSSIDDTDGYTMTSVLQQLSYFYT
  TMCQNGLDPELVRQAVKQLFFLIGAVTLNSLFLRKDMCSCRKGMQIRCNISYLEEWLKDK
  NLQNSLAKETLEPLSQAAWLLQVKKTTDSDAKEIYERCTSLSAVQIIKILNSYTPIDDFE
  KRVTPSFVRKVQALLNSREDSSQLMLDTKYLFQVTFPFTPSPHALEMIQIPSSFKLGFLN
  RL
• Function: May be involved in transferrin trafficking. Likely to power actin-based membrane trafficking in many physiologically crucial tissues.
• Tissue Specificity: Expressed chiefly in non-neuronal tissues. Particularly abundant in epithelial and glandular tissues including pancreas, prostate, mammary, stomach, colon and lung.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Pathogenic Escherichia coli infection (hsa05130)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Drug dependence	DIS9IXRC	Strong	Biomarker	[1]
Substance abuse	DIS327VW	Strong	Biomarker	[1]
Substance dependence	DISDRAAR	Strong	Biomarker	[1]
Diabetic retinopathy	DISHGUJM	moderate	Genetic Variation	[2]
Retinopathy	DISB4B0F	moderate	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Limited	Biomarker	[3]
Lewy body dementia	DISAE66J	Limited	Altered Expression	[3]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Unconventional myosin-Vc (MYO5C) decreases the response to substance of Arsenic trioxide.	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Unconventional myosin-Vc (MYO5C).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Unconventional myosin-Vc (MYO5C).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Unconventional myosin-Vc (MYO5C).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Unconventional myosin-Vc (MYO5C).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Unconventional myosin-Vc (MYO5C).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Unconventional myosin-Vc (MYO5C).	[9]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Unconventional myosin-Vc (MYO5C).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Unconventional myosin-Vc (MYO5C).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Unconventional myosin-Vc (MYO5C).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Unconventional myosin-Vc (MYO5C).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Unconventional myosin-Vc (MYO5C).	[15]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Unconventional myosin-Vc (MYO5C).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Unconventional myosin-Vc (MYO5C).	[10]

References

• [1] Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
• [2] Chromosome 15q21-22-related polymorphisms and haplotypes are associated with susceptibility to type-2 diabetic nonproliferative retinopathy.Genet Test Mol Biomarkers. 2012 May;16(5):442-8. doi: 10.1089/gtmb.2011.0092. Epub 2012 Mar 12.
• [3] Genes associated with the progression of neurofibrillary tangles in Alzheimer's disease.Transl Psychiatry. 2014 Jun 10;4(6):e396. doi: 10.1038/tp.2014.35.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [14] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [15] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [16] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.
• [17] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.