Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOAV4AR)

• DOT Name: Unconventional myosin-If (MYO1F)
• Synonyms: Myosin-Ie
• Gene Name: MYO1F
• Related Disease:
  Sensorineural hearing loss disorder
  Acute monocytic leukemia
  Adult acute monocytic leukemia
  Coronary heart disease
  Hyperlipidemia
  Primary cutaneous peripheral T-cell lymphoma not otherwise specified
  Neoplasm
  Nonsyndromic genetic hearing loss
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
• UniProt ID: MYO1F_HUMAN
• Pfam ID: PF00063 ; PF06017 ; PF00018
• Sequence:
  MGSKERFHWQSHNVKQSGVDDMVLLPQITEDAIAANLRKRFMDDYIFTYIGSVLISVNPF
  KQMPYFTDREIDLYQGAAQYENPPHIYALTDNMYRNMLIDCENQCVIISGESGAGKTVAA
  KYIMGYISKVSGGGEKVQHVKDIILQSNPLLEAFGNAKTVRNNNSSRFGKYFEIQFSRGG
  EPDGGKISNFLLEKSRVVMQNENERNFHIYYQLLEGASQEQRQNLGLMTPDYYYYLNQSD
  TYQVDGTDDRSDFGETLSAMQVIGIPPSIQQLVLQLVAGILHLGNISFCEDGNYARVESV
  DLLAFPAYLLGIDSGRLQEKLTSRKMDSRWGGRSESINVTLNVEQAAYTRDALAKGLYAR
  LFDFLVEAINRAMQKPQEEYSIGVLDIYGFEIFQKNGFEQFCINFVNEKLQQIFIELTLK
  AEQEEYVQEGIRWTPIQYFNNKVVCDLIENKLSPPGIMSVLDDVCATMHATGGGADQTLL
  QKLQAAVGTHEHFNSWSAGFVIHHYAGKVSYDVSGFCERNRDVLFSDLIELMQTSEQAFL
  RMLFPEKLDGDKKGRPSTAGSKIKKQANDLVATLMRCTPHYIRCIKPNETKRPRDWEENR
  VKHQVEYLGLKENIRVRRAGFAYRRQFAKFLQRYAILTPETWPRWRGDERQGVQHLLRAV
  NMEPDQYQMGSTKVFVKNPESLFLLEEVRERKFDGFARTIQKAWRRHVAVRKYEEMREEA
  SNILLNKKERRRNSINRNFVGDYLGLEERPELRQFLGKRERVDFADSVTKYDRRFKPIKR
  DLILTPKCVYVIGREKVKKGPEKGQVCEVLKKKVDIQALRGVSLSTRQDDFFILQEDAAD
  SFLESVFKTEFVSLLCKRFEEATRRPLPLTFSDTLQFRVKKEGWGGGGTRSVTFSRGFGD
  LAVLKVGGRTLTVSVGDGLPKSSKPTRKGMAKGKPRRSSQAPTRAAPAPPRGMDRNGVPP
  SARGGPLPLEIMSGGGTHRPPRGPPSTSLGASRRPRARPPSEHNTEFLNVPDQGMAGMQR
  KRSVGQRPVPGVGRPKPQPRTHGPRCRALYQYVGQDVDELSFNVNEVIEILMEDPSGWWK
  GRLHGQEGLFPGNYVEKI
• 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.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Pathogenic Escherichia coli infection (hsa05130)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Sensorineural hearing loss disorder	DISJV45Z	Definitive	Genetic Variation	[1]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[2]
Adult acute monocytic leukemia	DISG6BLX	Strong	Biomarker	[2]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[3]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[3]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	DIS5OHQF	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Disputed	Biomarker	[5]
Nonsyndromic genetic hearing loss	DISZX61P	Disputed	Autosomal dominant	[6]
Thyroid cancer	DIS3VLDH	Disputed	Biomarker	[5]
Thyroid gland carcinoma	DISMNGZ0	Disputed	Biomarker	[5]
Thyroid tumor	DISLVKMD	Disputed	Biomarker	[5]

2 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-If (MYO1F).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Unconventional myosin-If (MYO1F).	[12]

5 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 Unconventional myosin-If (MYO1F).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Unconventional myosin-If (MYO1F).	[9]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Unconventional myosin-If (MYO1F).	[10]
Coprexa	DMA0WEK	Phase 3	Coprexa increases the expression of Unconventional myosin-If (MYO1F).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Unconventional myosin-If (MYO1F).	[13]

References

• [1] 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.
• [2] The MYO1F, unconventional myosin type 1F, gene is fused to MLL in infant acute monocytic leukemia with a complex translocation involving chromosomes 7, 11, 19 and 22.Oncogene. 2005 Aug 4;24(33):5191-7. doi: 10.1038/sj.onc.1208711.
• [3] NCF2, MYO1F, S1PR4, and FCN1 as potential noninvasive diagnostic biomarkers in patients with obstructive coronary artery: A weighted gene co-expression network analysis.J Cell Biochem. 2019 Oct;120(10):18219-18235. doi: 10.1002/jcb.29128. Epub 2019 Jun 27.
• [4] Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas.Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):764-769. doi: 10.1073/pnas.1608839114. Epub 2017 Jan 6.
• [5] Mutant MYO1F alters the mitochondrial network and induces tumor proliferation in thyroid cancer.Int J Cancer. 2018 Oct 1;143(7):1706-1719. doi: 10.1002/ijc.31548. Epub 2018 May 7.
• [6] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [7] 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.
• [8] 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.
• [9] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [10] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [11] Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
• [12] 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.
• [13] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.