Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBSUOL8)

• DOT Name: Protein phosphatase methylesterase 1 (PPME1)
• Synonyms: PME-1; EC 3.1.1.89
• Gene Name: PPME1
• UniProt ID: PPME1_HUMAN
• PDB ID: 3C5V; 3C5W; 7SOY
• EC Number: 3.1.1.89
• Pfam ID: PF12697
• Sequence:
  MSALEKSMHLGRLPSRPPLPGSGGSQSGAKMRMGPGRKRDFSPVPWSQYFESMEDVEVEN
  ETGKDTFRVYKSGSEGPVLLLLHGGGHSALSWAVFTAAIISRVQCRIVALDLRSHGETKV
  KNPEDLSAETMAKDVGNVVEAMYGDLPPPIMLIGHSMGGAIAVHTASSNLVPSLLGLCMI
  DVVEGTAMDALNSMQNFLRGRPKTFKSLENAIEWSVKSGQIRNLESARVSMVGQVKQCEG
  ITSPEGSKSIVEGIIEEEEEDEEGSESISKRKKEDDMETKKDHPYTWRIELAKTEKYWDG
  WFRGLSNLFLSCPIPKLLLLAGVDRLDKDLTIGQMQGKFQMQVLPQCGHAVHEDAPDKVA
  EAVATFLIRHRFAEPIGGFQCVFPGC
• Function: Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme.
• Reactome Pathway: Cyclin A/B1/B2 associated events during G2/M transition (R-HSA-69273)
• BioCyc Pathway: MetaCyc:MONOMER-16514

Molecular Interaction Atlas (MIA) of This DOT

8 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 methylesterase 1 (PPME1).	[1]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein phosphatase methylesterase 1 (PPME1).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein phosphatase methylesterase 1 (PPME1).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein phosphatase methylesterase 1 (PPME1).	[4]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protein phosphatase methylesterase 1 (PPME1).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein phosphatase methylesterase 1 (PPME1).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Protein phosphatase methylesterase 1 (PPME1).	[5]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Protein phosphatase methylesterase 1 (PPME1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein phosphatase methylesterase 1 (PPME1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein phosphatase methylesterase 1 (PPME1).	[8]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [4] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [5] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [8] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [9] Morroniside-Induced PP2A Activation Antagonizes Tau Hyperphosphorylation in a Cellular Model of Neurodegeneration. J Alzheimers Dis. 2016;51(1):33-44. doi: 10.3233/JAD-150728.