Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOCFS3Q)

• DOT Name: Unconventional myosin-Ig (MYO1G)
• Gene Name: MYO1G
• Related Disease:
  Neoplasm
  Thyroid gland papillary carcinoma
  Influenza
  Graft-versus-host disease
• UniProt ID: MYO1G_HUMAN
• Pfam ID: PF00063 ; PF06017
• Sequence:
  MEDEEGPEYGKPDFVLLDQVTMEDFMRNLQLRFEKGRIYTYIGEVLVSVNPYQELPLYGP
  EAIARYQGRELYERPPHLYAVANAAYKAMKHRSRDTCIVISGESGAGKTEASKHIMQYIA
  AVTNPSQRAEVERVKDVLLKSTCVLEAFGNARTNRNHNSSRFGKYMDINFDFKGDPIGGH
  IHSYLLEKSRVLKQHVGERNFHAFYQLLRGSEDKQLHELHLERNPAVYNFTHQGAGLNMT
  VHSALDSDEQSHQAVTEAMRVIGFSPEEVESVHRILAAILHLGNIEFVETEEGGLQKEGL
  AVAEEALVDHVAELTATPRDLVLRSLLARTVASGGRELIEKGHTAAEASYARDACAKAVY
  QRLFEWVVNRINSVMEPRGRDPRRDGKDTVIGVLDIYGFEVFPVNSFEQFCINYCNEKLQ
  QLFIQLILKQEQEEYEREGITWQSVEYFNNATIVDLVERPHRGILAVLDEACSSAGTITD
  RIFLQTLDMHHRHHLHYTSRQLCPTDKTMEFGRDFRIKHYAGDVTYSVEGFIDKNRDFLF
  QDFKRLLYNSTDPTLRAMWPDGQQDITEVTKRPLTAGTLFKNSMVALVENLASKEPFYVR
  CIKPNEDKVAGKLDENHCRHQVAYLGLLENVRVRRAGFASRQPYSRFLLRYKMTCEYTWP
  NHLLGSDKAAVSALLEQHGLQGDVAFGHSKLFIRSPRTLVTLEQSRARLIPIIVLLLQKA
  WRGTLARWRCRRLRAIYTIMRWFRRHKVRAHLAELQRRFQAARQPPLYGRDLVWPLPPAV
  LQPFQDTCHALFCRWRARQLVKNIPPSDMPQIKAKVAAMGALQGLRQDWGCRRAWARDYL
  SSATDNPTASSLFAQRLKTLQDKDGFGAVLFSSHVRKVNRFHKIRNRALLLTDQHLYKLD
  PDRQYRVMRAVPLEAVTGLSVTSGGDQLVVLHARGQDDLVVCLHRSRPPLDNRVGELVGV
  LAAHCQGEGRTLEVRVSDCIPLSHRGVRRLISVEPRPEQPEPDFRCARGSFTLLWPSR
• Function: Unconventional myosin required during immune response for detection of rare antigen-presenting cells by regulating T-cell migration. Unconventional myosins are actin-based motor molecules with ATPase activity and serve in intracellular movements. Acts as a regulator of T-cell migration by generating membrane tension, enforcing cell-intrinsic meandering search, thereby enhancing detection of rare antigens during lymph-node surveillance, enabling pathogen eradication. Also required in B-cells, where it regulates different membrane/cytoskeleton-dependent processes. Involved in Fc-gamma receptor (Fc-gamma-R) phagocytosis; [Minor histocompatibility antigen HA-2]: Constitutes the minor histocompatibility antigen HA-2. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and their expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. HA-2 is restricted to MHC class I HLA-A*0201.
• Tissue Specificity: Specifically expressed in hematopoietic cells.
• KEGG Pathway:
  Motor proteins (hsa04814)
  Pathogenic Escherichia coli infection (hsa05130)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[1]
Influenza	DIS3PNU3	Strong	Biomarker	[2]
Graft-versus-host disease	DIS0QADF	moderate	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Unconventional myosin-Ig (MYO1G).	[4]
Cotinine	DMCEZ1B	Approved	Cotinine affects the methylation of Unconventional myosin-Ig (MYO1G).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Unconventional myosin-Ig (MYO1G).	[8]

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-Ig (MYO1G).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Unconventional myosin-Ig (MYO1G).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Unconventional myosin-Ig (MYO1G).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Unconventional myosin-Ig (MYO1G).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Unconventional myosin-Ig (MYO1G).	[11]

References

• [1] In-Depth Proteomics Analysis to Identify Biomarkers of Papillary Thyroid Cancer Patients Older Than 45 Years with Different Degrees of Lymph Node Metastases.Proteomics Clin Appl. 2019 Sep;13(5):e1900030. doi: 10.1002/prca.201900030. Epub 2019 Jun 7.
• [2] Insights into structural and inhibitory mechanisms of low pH-induced conformational change of influenza HA2 protein: a computational approach.J Mol Model. 2019 Mar 23;25(4):99. doi: 10.1007/s00894-019-3982-y.
• [3] Mismatch for the minor histocompatibility antigen HA-2 and GVHD occurrence in HLA-A*0201-positive Tunisian recipients of HSCs.Immunol Invest. 2010;39(6):611-20. doi: 10.3109/08820131003775029.
• [4] 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.
• [5] 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.
• [6] 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environ Health Perspect. 2012 Oct;120(10):1425-31. doi: 10.1289/ehp.1205412. Epub 2012 Jul 31.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [10] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [11] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.