Details of Drug Off-Target (DOT)

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

• DOT Name: Unconventional myosin-XIX (MYO19)
• Synonyms: Myosin head domain-containing protein 1
• Gene Name: MYO19
• Related Disease: Chronic renal failure
• UniProt ID: MYO19_HUMAN
• Pfam ID: PF00063
• Sequence:
  MLQQVNGHNPGSDGQAREYLREDLQEFLGGEVLLYKLDDLTRVNPVTLETVLRCLQARYM
  ADTFYTNAGCTLVALNPFKPVPQLYSPELMREYHAAPQPQKLKPHVFTVGEQTYRNVKSL
  IEPVNQSIVVSGESGAGKTWTSRCLMKFYAVVATSPASWESHKIAERIEQRILNSNPVME
  AFGNACTLRNNNSSRFGKFIQLQLNRAQQMTGAAVQTYLLEKTRVACQASSERNFHIFYQ
  ICKGASEDERLQWHLPEGAAFSWLPNPERSLEEDCFEVTREAMLHLGIDTPTQNNIFKVL
  AGLLHLGNIQFAASEDEAQPCQPMDDAKYSVRTAASLLGLPEDVLLEMVQIRTIRAGRQQ
  QVFRKPCARAECDTRRDCLAKLIYARLFDWLVSVINSSICADTDSWTTFIGLLDVYGFES
  FPDNSLEQLCINYANEKLQQHFVAHYLRAQQEEYAVEGLEWSFINYQDNQPCLDLIEGSP
  ISICSLINEECRLNRPSSAAQLQTRIETALAGSPCLGHNKLSREPSFIVVHYAGPVRYHT
  AGLVEKNKDPIPPELTRLLQQSQDPLLMGLFPTNPKEKTQEEPPGQSRAPVLTVVSKFKA
  SLEQLLQVLHSTTPHYIRCIKPNSQGQAQTFLQEEVLSQLEACGLVETIHISAAGFPIRV
  SHRNFVERYKLLRRLHPCTSSGPDSPYPAKGLPEWCPHSEEATLEPLIQDILHTLPVLTQ
  AAAITGDSAEAMPAPMHCGRTKVFMTDSMLELLECGRARVLEQCARCIQGGWRRHRHREQ
  ERQWRAVMLIQAAIRSWLTRKHIQRLHAAATVIKRAWQKWRIRMACLAAKELDGVEEKHF
  SQAPCSLSTSPLQTRLLEAIIRLWPLGLVLANTAMGVGSFQRKLVVWACLQLPRGSPSSY
  TVQTAQDQAGVTSIRALPQGSIKFHCRKSPLRYADICPEPSPYSITGFNQILLERHRLIH
  VTSSAFTGLG
• Function: Actin-based motor molecule with ATPase activity that localizes to the mitochondrion outer membrane. Motor protein that moves towards the plus-end of actin filaments. Required for mitochondrial inheritance during mitosis. May be involved in mitochondrial transport or positioning.
• Tissue Specificity: Widely expressed in multiple tissues and cell lines.
• KEGG Pathway: Motor proteins (hsa04814)
• Reactome Pathway:
  RHOT1 GTPase cycle (R-HSA-9013425)
  RHOT2 GTPase cycle (R-HSA-9013419)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic renal failure	DISGG7K6	Definitive	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Unconventional myosin-XIX (MYO19).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Unconventional myosin-XIX (MYO19).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Unconventional myosin-XIX (MYO19).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Unconventional myosin-XIX (MYO19).	[4]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Unconventional myosin-XIX (MYO19).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Unconventional myosin-XIX (MYO19).	[6]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Unconventional myosin-XIX (MYO19).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Unconventional myosin-XIX (MYO19).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Unconventional myosin-XIX (MYO19).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Unconventional myosin-XIX (MYO19).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Unconventional myosin-XIX (MYO19).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Unconventional myosin-XIX (MYO19).	[9]

References

• [1] A catalog of genetic loci associated with kidney function from analyses of a million individuals.Nat Genet. 2019 Jun;51(6):957-972. doi: 10.1038/s41588-019-0407-x. Epub 2019 May 31.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [5] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [8] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [9] 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.
• [10] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [11] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.