Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHL9ZKS)

• DOT Name: CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase, mitochondrial (PGS1)
• Synonyms: EC 2.7.8.5; Phosphatidylglycerophosphate synthase 1; PGP synthase 1
• Gene Name: PGS1
• Related Disease: Acute myelogenous leukaemia
• UniProt ID: PGPS1_HUMAN
• EC Number: 2.7.8.5
• Sequence:
  MAVAAAAAAGPVFWRRLLGLLPGRPGLAALLGRLSDRLGRNRDRQRRRSPWLLLAPLLSP
  AVPQVTSPPCCLCPEGVHRFQWIRNLVPEFGVSSSHVRVLSSPAEFFELMKGQIRVAKRR
  VVMASLYLGTGPLEQELVDCLESTLEKSLQAKFPSNLKVSILLDFTRGSRGRKNSRTMLL
  PLLRRFPEQVRVSLFHTPHLRGLLRLLIPERFNETIGLQHIKVYLFDNSVILSGANLSDS
  YFTNRQDRYVFLQDCAEIADFFTELVDAVGDVSLQLQGDDTVQVVDGMVHPYKGDRAEYC
  KAANKRVMDVINSARTRQQMLHAQTFHSNSLLTQEDAAAAGDRRPAPDTWIYPLIQMKPF
  EIQIDEIVTETLLTEAERGAKVYLTTGYFNLTQAYMDLVLGTRAEYQILLASPEVNGFFG
  AKGVAGAIPAAYVHIERQFFSEVCSLGQQERVQLQEYWRRGWTFHAKGLWLYLAGSSLPC
  LTLIGSPNFGYRSVHRDLEAQIAIVTENQALQQQLHQEQEQLYLRSGVVSSATFEQPSRQ
  VKLWVKMVTPLIKNFF
• Function: Functions in the biosynthesis of the anionic phospholipids phosphatidylglycerol and cardiolipin.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Synthesis of PG (R-HSA-1483148)
• BioCyc Pathway: MetaCyc:HS01560-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase, mitochondrial (PGS1).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase, mitochondrial (PGS1).	[4]

3 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 CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase, mitochondrial (PGS1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase, mitochondrial (PGS1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase, mitochondrial (PGS1).	[6]

References

• [1] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.