Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9WVC6N)

• DOT Name: Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1)
• Synonyms: EC 3.1.3.27; PTEN-like phosphatase; Phosphoinositide lipid phosphatase; Protein-tyrosine phosphatase mitochondrial 1; EC 3.1.3.16, EC 3.1.3.48
• Gene Name: PTPMT1
• Related Disease:
  Malaria
  Acute erythroid leukemia
  High blood pressure
  Lung cancer
  Lung carcinoma
  Advanced cancer
• UniProt ID: PTPM1_HUMAN
• EC Number: 3.1.3.16; 3.1.3.27; 3.1.3.48
• Pfam ID: PF00782
• Sequence:
  MAATALLEAGLARVLFYPTLLYTLFRGKVPGRAHRDWYHRIDPTVLLGALPLRSLTRQLV
  QDENVRGVITMNEEYETRFLCNSSQEWKRLGVEQLRLSTVDMTGIPTLDNLQKGVQFALK
  YQSLGQCVYVHCKAGRSRSATMVAAYLIQVHKWSPEEAVRAIAKIRSYIHIRPGQLDVLK
  EFHKQITARATKDGTFVISKT
• Function: Lipid phosphatase which dephosphorylates phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG). PGP is an essential intermediate in the biosynthetic pathway of cardiolipin, a mitochondrial-specific phospholipid regulating the membrane integrity and activities of the organelle. Has also been shown to display phosphatase activity toward phosphoprotein substrates, specifically mediates dephosphorylation of mitochondrial proteins, thereby playing an essential role in ATP production. Has probably a preference for proteins phosphorylated on Ser and/or Thr residues compared to proteins phosphorylated on Tyr residues. Probably involved in regulation of insulin secretion in pancreatic beta cells. May prevent intrinsic apoptosis, probably by regulating mitochondrial membrane integrity.
• Reactome Pathway: Synthesis of PG (R-HSA-1483148)
• BioCyc Pathway: MetaCyc:HS03319-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Definitive	Biomarker	[1]
Acute erythroid leukemia	DISZFC1O	Strong	Altered Expression	[2]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[3]
Lung cancer	DISCM4YA	Strong	Biomarker	[4]
Lung carcinoma	DISTR26C	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1) affects the response to substance of Acetaminophen.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Phosphatidylglycerophosphatase and protein-tyrosine phosphatase 1 (PTPMT1).	[13]

References

• [1] From malaria to cancer: Computational drug repositioning of amodiaquine using PLIP interaction patterns.Sci Rep. 2017 Sep 12;7(1):11401. doi: 10.1038/s41598-017-11924-4.
• [2] Ptpmt1 induced by HIF-2 regulates the proliferation and glucose metabolism in erythroleukemia cells.Biochem Biophys Res Commun. 2016 Mar 18;471(4):459-65. doi: 10.1016/j.bbrc.2016.02.053. Epub 2016 Feb 17.
• [3] Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.Nat Genet. 2016 Oct;48(10):1162-70. doi: 10.1038/ng.3660. Epub 2016 Sep 12.
• [4] SRSF1 modulates PTPMT1 alternative splicing to regulate lung cancer cell radioresistance.EBioMedicine. 2018 Dec;38:113-126. doi: 10.1016/j.ebiom.2018.11.007. Epub 2018 Nov 11.
• [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] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] 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.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [12] 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.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.