Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV12NKE)

• DOT Name: Protein PALS2 (PALS2)
• Synonyms: MAGUK p55 subfamily member 6; Membrane protein, palmitoylated 6; Veli-associated MAGUK 1; VAM-1
• Gene Name: PALS2
• UniProt ID: PALS2_HUMAN
• Pfam ID: PF00625 ; PF02828 ; PF00595 ; PF07653
• Sequence:
  MQQVLENLTELPSSTGAEEIDLIFLKGIMENPIVKSLAKAHERLEDSKLEAVSDNNLELV
  NEILEDITPLINVDENVAELVGILKEPHFQSLLEAHDIVASKCYDSPPSSPEMNNSSINN
  QLLPVDAIRILGIHKRAGEPLGVTFRVENNDLVIARILHGGMIDRQGLLHVGDIIKEVNG
  HEVGNNPKELQELLKNISGSVTLKILPSYRDTITPQQVFVKCHFDYNPYNDNLIPCKEAG
  LKFSKGEILQIVNREDPNWWQASHVKEGGSAGLIPSQFLEEKRKAFVRRDWDNSGPFCGT
  ISSKKKKKMMYLTTRNAEFDRHEIQIYEEVAKMPPFQRKTLVLIGAQGVGRRSLKNRFIV
  LNPTRFGTTVPFTSRKPREDEKDGQAYKFVSRSEMEADIKAGKYLEHGEYEGNLYGTKID
  SILEVVQTGRTCILDVNPQALKVLRTSEFMPYVVFIAAPELETLRAMHKAVVDAGITTKL
  LTDSDLKKTVDESARIQRAYNHYFDLIIINDNLDKAFEKLQTAIEKLRMEPQWVPISWVY
• Tissue Specificity: Abundant in testis, brain, and kidney with lower levels detectable in other tissues.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Protein PALS2 (PALS2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein PALS2 (PALS2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein PALS2 (PALS2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein PALS2 (PALS2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Protein PALS2 (PALS2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein PALS2 (PALS2).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein PALS2 (PALS2).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein PALS2 (PALS2).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein PALS2 (PALS2).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Protein PALS2 (PALS2).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Protein PALS2 (PALS2).	[10]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Protein PALS2 (PALS2).	[11]
NVP-AUY922	DMTYXQF	Phase 2	NVP-AUY922 increases the expression of Protein PALS2 (PALS2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein PALS2 (PALS2).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein PALS2 (PALS2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein PALS2 (PALS2).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein PALS2 (PALS2).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein PALS2 (PALS2).	[17]

References

• [1] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] 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.
• [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] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [11] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [12] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [13] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [15] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.