Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8A75Q7)

• DOT Name: Mpv17-like protein (MPV17L)
• Synonyms: M-LP homolog; M-LPH
• Gene Name: MPV17L
• Related Disease: Hepatocellular carcinoma
• UniProt ID: MP17L_HUMAN
• Pfam ID: PF04117
• Sequence:
  MAGWWPALSRAARRHPWPTNVLLYGSLVSAGDALQQRLQGREANWRQTRRVATLVVTFHA
  NFNYVWLRLLERALPGRAPHALLAKLLCDQVVGAPIAVSAFYVGMSILQGKDDIFLDLKQ
  KFWNTYLSGLMYWPFVQLTNFSLVPVQWRTAYAGVCGFLWATFICFSQQSGDGTFKSAFT
  ILYTKGTSATEGYPKK
• Function: [Isoform 1]: Participates in reactive oxygen species metabolism by up- or down-regulation of the genes of antioxidant enzymes. Protective against the mitochondrial apoptotic cascade.
• Tissue Specificity: Isoform 1 is detected in the kidney (at protein level). Isoform 1 and isoform 2 are expressed in the kidney, heart, liver, lung, pancreas and skeletal muscle.
• KEGG Pathway: Peroxisome (hsa04146)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mpv17-like protein (MPV17L).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Mpv17-like protein (MPV17L).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Mpv17-like protein (MPV17L).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Mpv17-like protein (MPV17L).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mpv17-like protein (MPV17L).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Mpv17-like protein (MPV17L).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Mpv17-like protein (MPV17L).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Mpv17-like protein (MPV17L).	[7]

References

• [1] Knockout of Mpv17-Like Protein (M-LPH) Gene in Human Hepatoma Cells Results in Impairment of mtDNA Integrity through Reduction of TFAM, OGG1, and LIG3 at the Protein Levels.Oxid Med Cell Longev. 2018 Sep 17;2018:6956414. doi: 10.1155/2018/6956414. eCollection 2018.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [4] 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.
• [5] 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.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] 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.
• [9] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.