Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNPZ6HT)

• DOT Name: Liprin-alpha-3 (PPFIA3)
• Synonyms: Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-3; PTPRF-interacting protein alpha-3
• Gene Name: PPFIA3
• Related Disease:
  Gastric cancer
  Gonorrhea
  Stomach cancer
• UniProt ID: LIPA3_HUMAN
• Pfam ID: PF00536 ; PF07647
• Sequence:
  MMCEVMPTISEDGRRGSALGPDEAGGELERLMVTMLTERERLLETLREAQDGLATAQLRL
  RELGHEKDSLQRQLSIALPQEFAALTKELNLCREQLLEREEEIAELKAERNNTRLLLEHL
  ECLVSRHERSLRMTVVKRQAQSPGGVSSEVEVLKALKSLFEHHKALDEKVRERLRMALER
  VAVLEEELELSNQETLNLREQLSRRRSGLEEPGKDGDGQTLANGLGPGGDSNRRTAELEE
  ALERQRAEVCQLRERLAVLCRQMSQLEEELGTAHRELGKAEEANSKLQRDLKEALAQRED
  MEERITTLEKRYLSAQREATSLHDANDKLENELASKESLYRQSEEKSRQLAEWLDDAKQK
  LQQTLQKAETLPEIEAQLAQRVAALNKAEERHGNFEERLRQLEAQLEEKNQELQRARQRE
  KMNDDHNKRLSETVDKLLSESNERLQLHLKERMGALEEKNSLSEEIANMKKLQDELLLNK
  EQLLAEMERMQMEIDQLRGRPPSSYSRSLPGSALELRYSQAPTLPSGAHLDPYVAGSGRA
  GKRGRWSGVKEEPSKDWERSAPAGSIPPPFPGELDGSDEEEAEGMFGAELLSPSGQADVQ
  TLAIMLQEQLEAINKEIKLIQEEKETTEQRAEELESRVSSSGLDSLGRYRSSCSLPPSLT
  TSTLASPSPPSSGHSTPRLAPPSPAREGTDKANHVPKEEAGAPRGEGPAIPGDTPPPTPR
  SARLERMTQALALQAGSLEDGGPPRGSEGTPDSLHKAPKKKSIKSSIGRLFGKKEKGRMG
  PPGRDSSSLAGTPSDETLATDPLGLAKLTGPGDKDRRNKRKHELLEEACRQGLPFAAWDG
  PTVVSWLELWVGMPAWYVAACRANVKSGAIMANLSDTEIQREIGISNPLHRLKLRLAIQE
  MVSLTSPSAPASSRTSTGNVWMTHEEMESLTATTKPETKEISWEQILAYGDMNHEWVGND
  WLPSLGLPQYRSYFMESLVDARMLDHLNKKELRGQLKMVDSFHRVSLHYGIMCLKRLNYD
  RKDLERRREESQTQIRDVMVWSNERVMGWVSGLGLKEFATNLTESGVHGALLALDETFDY
  SDLALLLQIPTQNAQARQLLEKEFSNLISLGTDRRLDEDSAKSFSRSPSWRKMFREKDLR
  GVTPDSAEMLPPNFRSAAAGALGSPGLPLRKLQPEGQTSGSSRADGVSVRTYSC
• Function: May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates.
• Tissue Specificity: Predominantly expressed in brain . Also detected in sperm (at protein level) .
• Reactome Pathway:
  Norepinephrine Neurotransmitter Release Cycle (R-HSA-181430)
  Glutamate Neurotransmitter Release Cycle (R-HSA-210500)
  Dopamine Neurotransmitter Release Cycle (R-HSA-212676)
  Acetylcholine Neurotransmitter Release Cycle (R-HSA-264642)
  Receptor-type tyrosine-protein phosphatases (R-HSA-388844)
  Serotonin Neurotransmitter Release Cycle (R-HSA-181429)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Strong	Biomarker	[1]
Gonorrhea	DISQ5AO6	Strong	Posttranslational Modification	[1]
Stomach cancer	DISKIJSX	Strong	Biomarker	[1]

4 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 Liprin-alpha-3 (PPFIA3).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Liprin-alpha-3 (PPFIA3).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Liprin-alpha-3 (PPFIA3).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Liprin-alpha-3 (PPFIA3).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Liprin-alpha-3 (PPFIA3).	[4]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Liprin-alpha-3 (PPFIA3).	[5]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Liprin-alpha-3 (PPFIA3).	[6]

References

• [1] Detection of OSR2, VAV3, and PPFIA3 Methylation in the Serum of Patients with Gastric Cancer.Dis Markers. 2016;2016:5780538. doi: 10.1155/2016/5780538. Epub 2016 Apr 7.
• [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] 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] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [5] Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims. Mol Psychiatry. 2007 Jan;12(1):55-73. doi: 10.1038/sj.mp.4001914. Epub 2006 Oct 31.
• [6] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [7] 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.
• [8] 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.