Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT34BLXJ)

• DOT Name: Liprin-alpha-2 (PPFIA2)
• Synonyms: Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-2; PTPRF-interacting protein alpha-2
• Gene Name: PPFIA2
• Related Disease:
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Intellectual disability
  Acute myelogenous leukaemia
• UniProt ID: LIPA2_HUMAN
• PDB ID: 3TAC; 3TAD; 6IUH; 7D2E; 7D2G; 7D2H
• Pfam ID: PF00536 ; PF07647
• Sequence:
  MMCEVMPTINEDTPMSQRGSQSSGSDSDSHFEQLMVNMLDERDRLLDTLRETQESLSLAQ
  QRLQDVIYDRDSLQRQLNSALPQDIESLTGGLAGSKGADPPEFAALTKELNACREQLLEK
  EEEISELKAERNNTRLLLEHLECLVSRHERSLRMTVVKRQAQSPSGVSSEVEVLKALKSL
  FEHHKALDEKVRERLRVSLERVSALEEELAAANQEIVALREQNVHIQRKMASSEGSTESE
  HLEGMEPGQKVHEKRLSNGSIDSTDETSQIVELQELLEKQNYEMAQMKERLAALSSRVGE
  VEQEAETARKDLIKTEEMNTKYQRDIREAMAQKEDMEERITTLEKRYLSAQRESTSIHDM
  NDKLENELANKEAILRQMEEKNRQLQERLELAEQKLQQTMRKAETLPEVEAELAQRIAAL
  TKAEERHGNIEERMRHLEGQLEEKNQELQRARQREKMNEEHNKRLSDTVDRLLTESNERL
  QLHLKERMAALEEKNVLIQESETFRKNLEESLHDKERLAEEIEKLRSELDQLKMRTGSLI
  EPTIPRTHLDTSAELRYSVGSLVDSQSDYRTTKVIRRPRRGRMGVRRDEPKVKSLGDHEW
  NRTQQIGVLSSHPFESDTEMSDIDDDDRETIFSSMDLLSPSGHSDAQTLAMMLQEQLDAI
  NKEIRLIQEEKESTELRAEEIENRVASVSLEGLNLARVHPGTSITASVTASSLASSSPPS
  GHSTPKLTPRSPAREMDRMGVMTLPSDLRKHRRKIAVVEEDGREDKATIKCETSPPPTPR
  ALRMTHTLPSSYHNDARSSLSVSLEPESLGLGSANSSQDSLHKAPKKKGIKSSIGRLFGK
  KEKARLGQLRGFMETEAAAQESLGLGKLGTQAEKDRRLKKKHELLEEARRKGLPFAQWDG
  PTVVAWLELWLGMPAWYVAACRANVKSGAIMSALSDTEIQREIGISNPLHRLKLRLAIQE
  MVSLTSPSAPPTSRTPSGNVWVTHEEMENLAAPAKTKESEEGSWAQCPVFLQTLAYGDMN
  HEWIGNEWLPSLGLPQYRSYFMECLVDARMLDHLTKKDLRVHLKMVDSFHRTSLQYGIMC
  LKRLNYDRKELERRREASQHEIKDVLVWSNDRVIRWIQAIGLREYANNILESGVHGSLIA
  LDENFDYSSLALLLQIPTQNTQARQILEREYNNLLALGTERRLDESDDKNFRRGSTWRRQ
  FPPREVHGISMMPGSSETLPAGFRLTTTSGQSRKMTTDVASSRLQRLDNSTVRTYSC
• Function: Alters PTPRF cellular localization and induces PTPRF clustering. 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. In neuronal cells, is a scaffolding protein in the dendritic spines which acts as immobile postsynaptic post able to recruit KIF1A-driven dense core vesicles to dendritic spines.
• Tissue Specificity: Expressed only in brain.
• 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

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[1]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[1]
Intellectual disability	DISMBNXP	Disputed	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Liprin-alpha-2 (PPFIA2).	[4]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Liprin-alpha-2 (PPFIA2).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Liprin-alpha-2 (PPFIA2).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Liprin-alpha-2 (PPFIA2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Liprin-alpha-2 (PPFIA2).	[8]

References

• [1] Liprin-alpha2 gene, protein tyrosine phosphatase LAR interacting protein related gene, is downregulated by androgens in the human prostate cancer cell line LNCaP.Int J Mol Med. 2002 Aug;10(2):173-6.
• [2] SNP array screening of cryptic genomic imbalances in 450 Japanese subjects with intellectual disability and multiple congenital anomalies previously negative for large rearrangements.J Hum Genet. 2016 Apr;61(4):335-43. doi: 10.1038/jhg.2015.154. Epub 2016 Jan 7.
• [3] 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.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Liprin alfa 2 gene expression is increased by cannabis use and associated with neuropsychological function. Eur Neuropsychopharmacol. 2019 May;29(5):643-652. doi: 10.1016/j.euroneuro.2019.03.004. Epub 2019 Mar 15.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [8] 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.