Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFHEZX7)

• DOT Name: Pleckstrin homology domain-containing family B member 2 (PLEKHB2)
• Synonyms: PH domain-containing family B member 2; Evectin-2
• Gene Name: PLEKHB2
• UniProt ID: PKHB2_HUMAN
• PDB ID: 3AJ4; 3VIA
• Pfam ID: PF00169
• Sequence:
  MAFVKSGWLLRQSTILKRWKKNWFDLWSDGHLIYYDDQTRQNIEDKVHMPMDCINIRTGQ
  ECRDTQPPDGKSKDCMLQIVCRDGKTISLCAESTDDCLAWKFTLQDSRTNTAYVGSAVMT
  DETSVVSSPPPYTAYAAPAPEQAYGYGPYGGAYPPGTQVVYAANGQAYAVPYQYPYAGLY
  GQQPANQVIIRERYRDNDSDLALGMLAGAATGMALGSLFWVF
• Function: Involved in retrograde transport of recycling endosomes.

Molecular Interaction Atlas (MIA) of This DOT

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 Pleckstrin homology domain-containing family B member 2 (PLEKHB2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Pleckstrin homology domain-containing family B member 2 (PLEKHB2).	[8]

10 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 Pleckstrin homology domain-containing family B member 2 (PLEKHB2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pleckstrin homology domain-containing family B member 2 (PLEKHB2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Pleckstrin homology domain-containing family B member 2 (PLEKHB2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Pleckstrin homology domain-containing family B member 2 (PLEKHB2).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Pleckstrin homology domain-containing family B member 2 (PLEKHB2).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Pleckstrin homology domain-containing family B member 2 (PLEKHB2).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Pleckstrin homology domain-containing family B member 2 (PLEKHB2).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Pleckstrin homology domain-containing family B member 2 (PLEKHB2).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Pleckstrin homology domain-containing family B member 2 (PLEKHB2).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Pleckstrin homology domain-containing family B member 2 (PLEKHB2).	[11]

References

• [1] 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.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks. Mutagenesis. 2014 Jan;29(1):17-26.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] 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.
• [8] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [9] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.