Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNTYMW0)

• DOT Name: PRKR-interacting protein 1 (PRKRIP1)
• Gene Name: PRKRIP1
• UniProt ID: PKRI1_HUMAN
• PDB ID: 5XJC; 6ICZ; 6QDV; 7W5A; 7W5B; 8C6J
• Pfam ID: PF06658
• Sequence:
  MASPAASSVRPPRPKKEPQTLVIPKNAAEEQKLKLERLMKNPDKAVPIPEKMSEWAPRPP
  PEFVRDVMGSSAGAGSGEFHVYRHLRRREYQRQDYMDAMAEKQKLDAEFQKRLEKNKIAA
  EEQTAKRRKKRQKLKEKKLLAKKMKLEQKKQEGPGQPKEQGSSSSAEASGTEEEEEVPSF
  TMGR
• Function: Required for pre-mRNA splicing as component of the spliceosome. Binds double-stranded RNA. Inhibits EIF2AK2 kinase activity.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

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 decreases the methylation of PRKR-interacting protein 1 (PRKRIP1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of PRKR-interacting protein 1 (PRKRIP1).	[8]

8 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 PRKR-interacting protein 1 (PRKRIP1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of PRKR-interacting protein 1 (PRKRIP1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PRKR-interacting protein 1 (PRKRIP1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of PRKR-interacting protein 1 (PRKRIP1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of PRKR-interacting protein 1 (PRKRIP1).	[6]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of PRKR-interacting protein 1 (PRKRIP1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of PRKR-interacting protein 1 (PRKRIP1).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of PRKR-interacting protein 1 (PRKRIP1).	[10]

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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [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.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.