Details of Drug Off-Target (DOT)

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

• DOT Name: Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (PPIL6)
• Synonyms: PPIase; Cyclophilin-like protein PPIL6; Rotamase PPIL6
• Gene Name: PPIL6
• Related Disease:
  Abscess
  Gastric disease
  Non-insulin dependent diabetes
  Parkinson disease
• UniProt ID: PPIL6_HUMAN
• PDB ID: 8J07
• Pfam ID: PF00160
• Sequence:
  MARPQPCGPPHARCGSPSLPERPLQVKVVGLFSCPNFQIAKSAAENLKNNHPSKFEDPIL
  VPLQEFAWHQYLQEKKRELKNETWEYSSSVISFVNGQFLGDALDLQKWAHEVWDIVDIKP
  SALYDALTEDFSAKFLRDTKHDFVFLDICIDSSPIGRLIFELYCDVCPKTCKNFQVLCTG
  KAGFSQRGIRLHYKNSIFHRIVQNGWIQGGDIVYGKGDNGESIYGPTFEDENFSVPHNKR
  GVLGMANKGRHSNGSQFYITLQATPYLDRKFVAFGQLIEGTEVLKQLELVPTQNERPIHM
  CRITDSGDPYA
• Function: Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abscess	DISAP982	Strong	Biomarker	[1]
Gastric disease	DISNZNTG	Strong	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[3]
Parkinson disease	DISQVHKL	Strong	Biomarker	[4]

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 Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (PPIL6).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (PPIL6).	[13]

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 Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (PPIL6).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (PPIL6).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (PPIL6).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (PPIL6).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (PPIL6).	[9]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (PPIL6).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (PPIL6).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (PPIL6).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (PPIL6).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Probable inactive peptidyl-prolyl cis-trans isomerase-like 6 (PPIL6).	[14]

References

• [1] Novel Regulation of Alpha-Toxin and the Phenol-Soluble Modulins by Peptidyl-Prolyl cis/trans Isomerase Enzymes in Staphylococcus aureus.Toxins (Basel). 2019 Jun 16;11(6):343. doi: 10.3390/toxins11060343.
• [2] Differential Proteomic Analysis Reveals Protein Networks and Pathways that May Contribute to Helicobacter pylori FKBP-Type PPIase-Associated Gastric Diseases.Proteomics Clin Appl. 2018 May;12(3):e1700127. doi: 10.1002/prca.201700127. Epub 2017 Dec 5.
• [3] Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.Diabetes. 2013 May;62(5):1746-55. doi: 10.2337/db12-1077. Epub 2013 Jan 8.
• [4] The Molecular Basis of the Interaction of CyclophilinA with -Synuclein.Angew Chem Int Ed Engl. 2020 Mar 27;59(14):5643-5646. doi: 10.1002/anie.201914878. Epub 2020 Jan 29.
• [5] 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.
• [6] 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.
• [7] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [10] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [11] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [12] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [13] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [14] 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.