Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD80K5X)

• DOT Name: Protein Mis18-alpha (MIS18A)
• Synonyms: FAPP1-associated protein 1
• Gene Name: MIS18A
• UniProt ID: MS18A_HUMAN
• PDB ID: 7SFY; 7SFZ
• Pfam ID: PF03226
• Sequence:
  MAGVRSLRCSRGCAGGCECGDKGKCSDSSLLGKRLSEDSSRHQLLQKWASMWSSMSEDAS
  VADMERAQLEEEAAAAEERPLVFLCSGCRRPLGDSLSWVASQEDTNCILLRCVSCNVSVD
  KEQKLSKREKENGCVLETLCCAGCSLNLGYVYRCTPKNLDYKRDLFCLSVEAIESYVLGS
  SEKQIVSEDKELFNLESRVEIEKSLTQMEDVLKALQMKLWEAESKLSFATCKS
• Function: Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis.
• Tissue Specificity: Detected in testis.
• Reactome Pathway: Deposition of new CENPA-containing nucleosomes at the centromere (R-HSA-606279)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein Mis18-alpha (MIS18A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein Mis18-alpha (MIS18A).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein Mis18-alpha (MIS18A).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein Mis18-alpha (MIS18A).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Protein Mis18-alpha (MIS18A).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein Mis18-alpha (MIS18A).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Protein Mis18-alpha (MIS18A).	[6]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Protein Mis18-alpha (MIS18A).	[7]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Protein Mis18-alpha (MIS18A).	[8]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Protein Mis18-alpha (MIS18A).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein Mis18-alpha (MIS18A).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein Mis18-alpha (MIS18A).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein Mis18-alpha (MIS18A).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein Mis18-alpha (MIS18A).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein Mis18-alpha (MIS18A).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein Mis18-alpha (MIS18A).	[16]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 increases the expression of Protein Mis18-alpha (MIS18A).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Protein Mis18-alpha (MIS18A).	[13]

References

• [1] 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.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [6] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [7] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [8] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [9] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [10] 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.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Gene expression profiles in HPV-immortalized human cervical cells treated with the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Chem Biol Interact. 2009 Feb 12;177(3):173-80. doi: 10.1016/j.cbi.2008.10.051. Epub 2008 Nov 6.