Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9C76GS)

• DOT Name: Phosphopantothenoylcysteine decarboxylase (PPCDC)
• Synonyms: PPC-DC; EC 4.1.1.36; CoaC
• Gene Name: PPCDC
• Related Disease:
  Autism
  Breast carcinoma
  Rheumatoid arthritis
• UniProt ID: COAC_HUMAN
• PDB ID: 1QZU
• EC Number: 4.1.1.36
• Pfam ID: PF02441
• Sequence:
  MEPKASCPAAAPLMERKFHVLVGVTGSVAALKLPLLVSKLLDIPGLEVAVVTTERAKHFY
  SPQDIPVTLYSDADEWEIWKSRSDPVLHIDLRRWADLLLVAPLDANTLGKVASGICDNLL
  TCVMRAWDRSKPLLFCPAMNTAMWEHPITAQQVDQLKAFGYVEIPCVAKKLVCGDEGLGA
  MAEVGTIVDKVKEVLFQHSGFQQS
• Function: Catalyzes the decarboxylation of the cysteine moiety of 4-phosphopantothenoylcysteine to form 4'-phosphopantotheine and this reaction forms part of the biosynthesis of coenzyme A.
• KEGG Pathway:
  Pantothe.te and CoA biosynthesis (hsa00770)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Coenzyme A biosynthesis (R-HSA-196783)
• BioCyc Pathway: MetaCyc:HS13735-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Phosphopantothenoylcysteine decarboxylase (PPCDC).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Phosphopantothenoylcysteine decarboxylase (PPCDC).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Phosphopantothenoylcysteine decarboxylase (PPCDC).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Phosphopantothenoylcysteine decarboxylase (PPCDC).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Phosphopantothenoylcysteine decarboxylase (PPCDC).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Phosphopantothenoylcysteine decarboxylase (PPCDC).	[8]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Phosphopantothenoylcysteine decarboxylase (PPCDC).	[10]

References

• [1] SCAMP5, NBEA and AMISYN: three candidate genes for autism involved in secretion of large dense-core vesicles.Hum Mol Genet. 2010 Apr 1;19(7):1368-78. doi: 10.1093/hmg/ddq013. Epub 2010 Jan 12.
• [2] Genetic predictors of chemotherapy-related amenorrhea inwomen with breast cancer.Fertil Steril. 2019 Oct;112(4):731-739.e1. doi: 10.1016/j.fertnstert.2019.05.018. Epub 2019 Jul 29.
• [3] A genetic association study of carotid intima-media thickness (CIMT) and plaque in Mexican Americans and European Americans with rheumatoid arthritis.Atherosclerosis. 2018 Apr;271:92-101. doi: 10.1016/j.atherosclerosis.2017.11.024. Epub 2017 Nov 26.
• [4] 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.
• [5] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] 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.
• [10] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.