Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPG10KS)

• DOT Name: Pleckstrin homology domain-containing family J member 1 (PLEKHJ1)
• Synonyms: PH domain-containing family J member 1; Guanine nucleotide-releasing protein x
• Gene Name: PLEKHJ1
• UniProt ID: PKHJ1_HUMAN
• Pfam ID: PF00169
• Sequence:
  MRYNEKELQALSRQPAEMAAELGMRGPKKGSVLKRRLVKLVVNFLFYFRTDEAEPVGALL
  LERCRVVREEPGTFSISFIEDPERKYHFECSSEEQCQEWMEALRRASYEFMRRSLIFYRN
  EIRKVTGKDPLEQFGISEEARFQLSGLQA
• Tissue Specificity: Expressed in testis and liver.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Pleckstrin homology domain-containing family J member 1 (PLEKHJ1) affects the response to substance of Acetaminophen.	[9]

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 J member 1 (PLEKHJ1).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Pleckstrin homology domain-containing family J member 1 (PLEKHJ1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Pleckstrin homology domain-containing family J member 1 (PLEKHJ1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pleckstrin homology domain-containing family J member 1 (PLEKHJ1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pleckstrin homology domain-containing family J member 1 (PLEKHJ1).	[4]
Selenium	DM25CGV	Approved	Selenium increases the expression of Pleckstrin homology domain-containing family J member 1 (PLEKHJ1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Pleckstrin homology domain-containing family J member 1 (PLEKHJ1).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Pleckstrin homology domain-containing family J member 1 (PLEKHJ1).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Pleckstrin homology domain-containing family J member 1 (PLEKHJ1).	[8]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.