Details of Drug Off-Target (DOT)

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

• DOT Name: Protein phosphatase PTC7 homolog (PPTC7)
• Synonyms: EC 3.1.3.16; T-cell activation protein phosphatase 2C; TA-PP2C; T-cell activation protein phosphatase 2C-like
• Gene Name: PPTC7
• Related Disease: Mitochondrial disease
• UniProt ID: PPTC7_HUMAN
• EC Number: 3.1.3.16
• Pfam ID: PF07228
• Sequence:
  MFSVLSYGRLVARAVLGGLSQTDPRAGGGGGGDYGLVTAGCGFGKDFRKGLLKKGACYGD
  DACFVARHRSADVLGVADGVGGWRDYGVDPSQFSGTLMRTCERLVKEGRFVPSNPIGILT
  TSYCELLQNKVPLLGSSTACIVVLDRTSHRLHTANLGDSGFLVVRGGEVVHRSDEQQHYF
  NTPFQLSIAPPEAEGVVLSDSPDAADSTSFDVQLGDIILTATDGLFDNMPDYMILQELKK
  LKNSNYESIQQTARSIAEQAHELAYDPNYMSPFAQFACDNGLNVRGGKPDDITVLLSIVA
  EYTD
• Function: Protein phosphatase which positively regulates biosynthesis of the ubiquinone, coenzyme Q. Dephosphorylates the ubiquinone biosynthesis protein COQ7 which is likely to lead to its activation.
• Tissue Specificity: Expressed in keratinocytes (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial disease	DISKAHA3	Strong	Altered Expression	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorpyrifos	DMKPUI6	Investigative	Protein phosphatase PTC7 homolog (PPTC7) decreases the response to substance of Chlorpyrifos.	[13]

9 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 phosphatase PTC7 homolog (PPTC7).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein phosphatase PTC7 homolog (PPTC7).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein phosphatase PTC7 homolog (PPTC7).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein phosphatase PTC7 homolog (PPTC7).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein phosphatase PTC7 homolog (PPTC7).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protein phosphatase PTC7 homolog (PPTC7).	[8]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Protein phosphatase PTC7 homolog (PPTC7).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein phosphatase PTC7 homolog (PPTC7).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein phosphatase PTC7 homolog (PPTC7).	[12]

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 Protein phosphatase PTC7 homolog (PPTC7).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein phosphatase PTC7 homolog (PPTC7).	[10]

References

• [1] The mitochondrial phosphatase PPTC7 orchestrates mitochondrial metabolism regulating coenzyme Q(10) biosynthesis.Biochim Biophys Acta Bioenerg. 2018 Nov;1859(11):1235-1248. doi: 10.1016/j.bbabio.2018.09.369. Epub 2018 Sep 26.
• [2] 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.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] 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.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Application of human haploid cell genetic screening model in identifying the genes required for resistance to environmental toxicants: Chlorpyrifos as a case study. J Pharmacol Toxicol Methods. 2015 Nov-Dec;76:76-82. doi: 10.1016/j.vascn.2015.08.154. Epub 2015 Aug 20.