Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT69L39Y)

• DOT Name: Unconventional myosin-Ic (MYO1C)
• Synonyms: Myosin I beta; MMI-beta; MMIb
• Gene Name: MYO1C
• Related Disease:
  Breast cancer
  Breast carcinoma
  Metastatic malignant neoplasm
  Metastatic prostate carcinoma
  Multiple sclerosis
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Sensorineural hearing loss disorder
  Adult glioblastoma
  Atrial fibrillation
  Familial atrial fibrillation
  Glioblastoma multiforme
  Autosomal dominant nonsyndromic hearing loss
  Autosomal dominant nonsyndromic hearing loss 1
• UniProt ID: MYO1C_HUMAN
• PDB ID: 4BYF
• Pfam ID: PF00612 ; PF00063 ; PF06017
• Sequence:
  MALQVELVPTGEIIRVVHPHRPCKLALGSDGVRVTMESALTARDRVGVQDFVLLENFTSE
  AAFIENLRRRFRENLIYTYIGPVLVSVNPYRDLQIYSRQHMERYRGVSFYEVPPHLFAVA
  DTVYRALRTERRDQAVMISGESGAGKTEATKRLLQFYAETCPAPERGGAVRDRLLQSNPV
  LEAFGNAKTLRNDNSSRFGKYMDVQFDFKGAPVGGHILSYLLEKSRVVHQNHGERNFHIF
  YQLLEGGEEETLRRLGLERNPQSYLYLVKGQCAKVSSINDKSDWKVVRKALTVIDFTEDE
  VEDLLSIVASVLHLGNIHFAANEESNAQVTTENQLKYLTRLLSVEGSTLREALTHRKIIA
  KGEELLSPLNLEQAAYARDALAKAVYSRTFTWLVGKINRSLASKDVESPSWRSTTVLGLL
  DIYGFEVFQHNSFEQFCINYCNEKLQQLFIELTLKSEQEEYEAEGIAWEPVQYFNNKIIC
  DLVEEKFKGIISILDEECLRPGEATDLTFLEKLEDTVKHHPHFLTHKLADQRTRKSLGRG
  EFRLLHYAGEVTYSVTGFLDKNNDLLFRNLKETMCSSKNPIMSQCFDRSELSDKKRPETV
  ATQFKMSLLQLVEILQSKEPAYVRCIKPNDAKQPGRFDEVLIRHQVKYLGLLENLRVRRA
  GFAYRRKYEAFLQRYKSLCPETWPTWAGRPQDGVAVLVRHLGYKPEEYKMGRTKIFIRFP
  KTLFATEDALEVRRQSLATKIQAAWRGFHWRQKFLRVKRSAICIQSWWRGTLGRRKAAKR
  KWAAQTIRRLIRGFVLRHAPRCPENAFFLDHVRTSFLLNLRRQLPQNVLDTSWPTPPPAL
  REASELLRELCIKNMVWKYCRSISPEWKQQLQQKAVASEIFKGKKDNYPQSVPRLFISTR
  LGTDEISPRVLQALGSEPIQYAVPVVKYDRKGYKPRSRQLLLTPNAVVIVEDAKVKQRID
  YANLTGISVSSLSDSLFVLHVQRADNKQKGDVVLQSDHVIETLTKTALSANRVNSININQ
  GSITFAGGPGRDGTIDFTPGSELLITKAKNGHLAVVAPRLNSR
• Function: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Involved in glucose transporter recycling in response to insulin by regulating movement of intracellular GLUT4-containing vesicles to the plasma membrane. Component of the hair cell's (the sensory cells of the inner ear) adaptation-motor complex. Acts as a mediator of adaptation of mechanoelectrical transduction in stereocilia of vestibular hair cells. Binds phosphoinositides and links the actin cytoskeleton to cellular membranes; [Isoform 3]: Involved in regulation of transcription. Associated with transcriptional active ribosomal genes. Appears to cooperate with the WICH chromatin-remodeling complex to facilitate transcription. Necessary for the formation of the first phosphodiester bond during transcription initiation.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Pathogenic Escherichia coli infection (hsa05130)
• Reactome Pathway:
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)
  Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[2]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Altered Expression	[3]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Genetic Variation	[5]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[6]
Atrial fibrillation	DIS15W6U	moderate	Biomarker	[7]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[7]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[6]
Autosomal dominant nonsyndromic hearing loss	DISYC1G0	Supportive	Autosomal dominant	[8]
Autosomal dominant nonsyndromic hearing loss 1	DISDZ6CC	Disputed	Biomarker	[9]

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 Unconventional myosin-Ic (MYO1C).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Unconventional myosin-Ic (MYO1C).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Unconventional myosin-Ic (MYO1C).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Unconventional myosin-Ic (MYO1C).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Unconventional myosin-Ic (MYO1C).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Unconventional myosin-Ic (MYO1C).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Unconventional myosin-Ic (MYO1C).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Unconventional myosin-Ic (MYO1C).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Unconventional myosin-Ic (MYO1C).	[16]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Unconventional myosin-Ic (MYO1C).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Unconventional myosin-Ic (MYO1C).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Unconventional myosin-Ic (MYO1C).	[21]

References

• [1] Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network.J Exp Clin Cancer Res. 2019 Nov 7;38(1):457. doi: 10.1186/s13046-019-1449-8.
• [2] Selective expression of myosin IC Isoform A in mouse and human cell lines and mouse prostate cancer tissues.PLoS One. 2014 Sep 26;9(9):e108609. doi: 10.1371/journal.pone.0108609. eCollection 2014.
• [3] Myosin isoform expressed in metastatic prostate cancer stimulates cell invasion.Sci Rep. 2017 Aug 16;7(1):8476. doi: 10.1038/s41598-017-09158-5.
• [4] Monodisperse magnetic poly(glycidyl methacrylate) microspheres for isolation of autoantibodies with affinity for the 46kDa form of unconventional Myo1C present in autoimmune patients.Mikrochim Acta. 2018 Apr 23;185(5):262. doi: 10.1007/s00604-018-2807-5.
• [5] Crystal structure of human myosin 1c--the motor in GLUT4 exocytosis: implications for Ca2+ regulation and 14-3-3 binding.J Mol Biol. 2014 May 15;426(10):2070-81. doi: 10.1016/j.jmb.2014.03.004. Epub 2014 Mar 14.
• [6] The SHIP2 interactor Myo1c is required for cell migration in 1321 N1 glioblastoma cells.Biochem Biophys Res Commun. 2016 Aug 5;476(4):508-514. doi: 10.1016/j.bbrc.2016.05.154. Epub 2016 May 28.
• [7] Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.Nat Genet. 2018 Sep;50(9):1234-1239. doi: 10.1038/s41588-018-0171-3. Epub 2018 Jul 30.
• [8] Are MYO1C and MYO1F associated with hearing loss?. Biochim Biophys Acta. 2009 Jan;1792(1):27-32. doi: 10.1016/j.bbadis.2008.10.017. Epub 2008 Nov 5.
• [9] Myo1c mutations associated with hearing loss cause defects in the interaction with nucleotide and actin.Cell Mol Life Sci. 2011 Jan;68(1):139-50. doi: 10.1007/s00018-010-0448-x. Epub 2010 Jul 17.
• [10] 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.
• [11] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [12] 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.
• [13] 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.
• [14] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [15] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [16] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [17] Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells. J Biochem Mol Toxicol. 2020 Oct;34(10):e22547. doi: 10.1002/jbt.22547. Epub 2020 Jun 26.
• [18] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [19] 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.
• [20] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [21] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.