Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP2RGPN)

• DOT Name: Unconventional myosin-Id (MYO1D)
• Gene Name: MYO1D
• Related Disease:
  Autism
  Colitis
  Neoplasm
  Refractive error
  Schizophrenia
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Chronic obstructive pulmonary disease
  Retinitis pigmentosa 1
• UniProt ID: MYO1D_HUMAN
• Pfam ID: PF00612 ; PF00063 ; PF06017
• Sequence:
  MAEQESLEFGKADFVLMDTVSMPEFMANLRLRFEKGRIYTFIGEVVVSVNPYKLLNIYGR
  DTIEQYKGRELYERPPHLFAIADAAYKAMKRRSKDTCIVISGESGAGKTEASKYIMQYIA
  AITNPSQRAEVERVKNMLLKSNCVLEAFGNAKTNRNDNSSRFGKYMDINFDFKGDPIGGH
  INNYLLEKSRVIVQQPGERSFHSFYQLLQGGSEQMLRSLHLQKSLSSYNYIHVGAQLKSS
  INDAAEFRVVADAMKVIGFKPEEIQTVYKILAAILHLGNLKFVVDGDTPLIENGKVVSII
  AELLSTKTDMVEKALLYRTVATGRDIIDKQHTEQEASYGRDAFAKAIYERLFCWIVTRIN
  DIIEVKNYDTTIHGKNTVIGVLDIYGFEIFDNNSFEQFCINYCNEKLQQLFIQLVLKQEQ
  EEYQREGIPWKHIDYFNNQIIVDLVEQQHKGIIAILDDACMNVGKVTDEMFLEALNSKLG
  KHAHFSSRKLCASDKILEFDRDFRIRHYAGDVVYSVIGFIDKNKDTLFQDFKRLMYNSSN
  PVLKNMWPEGKLSITEVTKRPLTAATLFKNSMIALVDNLASKEPYYVRCIKPNDKKSPQI
  FDDERCRHQVEYLGLLENVRVRRAGFAFRQTYEKFLHRYKMISEFTWPNHDLPSDKEAVK
  KLIERCGFQDDVAYGKTKIFIRTPRTLFTLEELRAQMLIRIVLFLQKVWRGTLARMRYKR
  TKAALTIIRYYRRYKVKSYIHEVARRFHGVKTMRDYGKHVKWPSPPKVLRRFEEALQTIF
  NRWRASQLIKSIPASDLPQVRAKVAAVEMLKGQRADLGLQRAWEGNYLASKPDTPQTSGT
  FVPVANELKRKDKYMNVLFSCHVRKVNRFSKVEDRAIFVTDRHLYKMDPTKQYKVMKTIP
  LYNLTGLSVSNGKDQLVVFHTKDNKDLIVCLFSKQPTHESRIGELVGVLVNHFKSEKRHL
  QVNVTNPVQCSLHGKKCTVSVETRLNQPQPDFTKNRSGFILSVPGN
• Function: Unconventional myosin that functions as actin-based motor protein with ATPase activity. Plays a role in endosomal protein trafficking, and especially in the transfer of cargo proteins from early to recycling endosomes. Required for normal planar cell polarity in ciliated tracheal cells, for normal rotational polarity of cilia, and for coordinated, unidirectional ciliary movement in the trachea. Required for normal, polarized cilia organization in brain ependymal epithelial cells.
• Tissue Specificity: Expressed in many tissues. Highest levels in brain, followed by lung and ovary; expression is lowest in spleen.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Pathogenic Escherichia coli infection (hsa05130)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Biomarker	[1]
Colitis	DISAF7DD	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Refractive error	DISWNEQ1	Strong	Genetic Variation	[4]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[5]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[6]
Breast cancer	DIS7DPX1	moderate	Biomarker	[7]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[7]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Genetic Variation	[8]
Retinitis pigmentosa 1	DISSLQPP	Limited	Altered Expression	[9]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Unconventional myosin-Id (MYO1D) affects the response to substance of Topotecan.	[25]
Cycloheximide	DMGDA3C	Investigative	Unconventional myosin-Id (MYO1D) affects the response to substance of Cycloheximide.	[26]

4 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-Id (MYO1D).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Unconventional myosin-Id (MYO1D).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Unconventional myosin-Id (MYO1D).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Unconventional myosin-Id (MYO1D).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Unconventional myosin-Id (MYO1D).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Unconventional myosin-Id (MYO1D).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Unconventional myosin-Id (MYO1D).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Unconventional myosin-Id (MYO1D).	[15]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Unconventional myosin-Id (MYO1D).	[16]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Unconventional myosin-Id (MYO1D).	[17]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Unconventional myosin-Id (MYO1D).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Unconventional myosin-Id (MYO1D).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Unconventional myosin-Id (MYO1D).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Unconventional myosin-Id (MYO1D).	[23]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone affects the expression of Unconventional myosin-Id (MYO1D).	[24]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Unconventional myosin-Id (MYO1D).	[19]

References

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• [2] The class I myosin MYO1D binds to lipid and protects against colitis.Dis Model Mech. 2018 Sep 27;11(9):dmm035923. doi: 10.1242/dmm.035923.
• [3] Plasma Membrane Localization of Apoptotic Caspases for Non-apoptotic Functions.Dev Cell. 2018 May 21;45(4):450-464.e3. doi: 10.1016/j.devcel.2018.04.020.
• [4] Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia.Nat Genet. 2013 Mar;45(3):314-8. doi: 10.1038/ng.2554. Epub 2013 Feb 10.
• [5] Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.Eur Arch Psychiatry Clin Neurosci. 2009 Apr;259(3):151-63. doi: 10.1007/s00406-008-0847-2. Epub 2009 Jan 22.
• [6] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [7] MYO1D binds with kinase domain of the EGFR family to anchor them to plasma membrane before their activation and contributes carcinogenesis.Oncogene. 2019 Dec;38(49):7416-7432. doi: 10.1038/s41388-019-0954-8. Epub 2019 Aug 16.
• [8] Genome-wide association identifies regulatory Loci associated with distinct local histogram emphysema patterns.Am J Respir Crit Care Med. 2014 Aug 15;190(4):399-409. doi: 10.1164/rccm.201403-0569OC.
• [9] Isobaric Tags for Relative and Absolute Quantitation-Based Proteomic Analysis of Patent and Constricted Ductus Arteriosus Tissues Confirms the Systemic Regulation of Ductus Arteriosus Closure.J Cardiovasc Pharmacol. 2015 Aug;66(2):204-13. doi: 10.1097/FJC.0000000000000266.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [12] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] 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.
• [15] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [16] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [17] 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.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [24] 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.
• [25] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [26] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.