Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0GPU73)

• DOT Name: Peptidyl-prolyl cis-trans isomerase-like 3 (PPIL3)
• Synonyms: PPIase; EC 5.2.1.8; Cyclophilin J; CyPJ; Cyclophilin-like protein PPIL3; Rotamase PPIL3
• Gene Name: PPIL3
• Related Disease:
  Abscess
  Carcinoma of liver and intrahepatic biliary tract
  Gastric adenocarcinoma
  Gastric disease
  Glioma
  Liver cancer
  Neoplasm
  Parkinson disease
  Small lymphocytic lymphoma
  Advanced cancer
  Hepatocellular carcinoma
• UniProt ID: PPIL3_HUMAN
• PDB ID: 1XYH; 2OJU; 2OK3; 8C6J
• EC Number: 5.2.1.8
• Pfam ID: PF00160
• Sequence:
  MSVTLHTDVGDIKIEVFCERTPKTCENFLALCASNYYNGCIFHRNIKGFMVQTGDPTGTG
  RGGNSIWGKKFEDEYSEYLKHNVRGVVSMANNGPNTNGSQFFITYGKQPHLDMKYTVFGK
  VIDGLETLDELEKLPVNEKTYRPLNDVHIKDITIHANPFAQ
• Function: PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. May be involved in pre-mRNA splicing.
• Tissue Specificity: Ubiquitous. Detected at low levels.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abscess	DISAP982	Strong	Biomarker	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[2]
Gastric adenocarcinoma	DISWWLTC	Strong	Biomarker	[3]
Gastric disease	DISNZNTG	Strong	Biomarker	[4]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
Liver cancer	DISDE4BI	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Parkinson disease	DISQVHKL	Strong	Biomarker	[6]
Small lymphocytic lymphoma	DIS30POX	Disputed	Genetic Variation	[7]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Peptidyl-prolyl cis-trans isomerase-like 3 (PPIL3).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Peptidyl-prolyl cis-trans isomerase-like 3 (PPIL3).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Peptidyl-prolyl cis-trans isomerase-like 3 (PPIL3).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Peptidyl-prolyl cis-trans isomerase-like 3 (PPIL3).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Peptidyl-prolyl cis-trans isomerase-like 3 (PPIL3).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Peptidyl-prolyl cis-trans isomerase-like 3 (PPIL3).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Peptidyl-prolyl cis-trans isomerase-like 3 (PPIL3).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Peptidyl-prolyl cis-trans isomerase-like 3 (PPIL3).	[15]

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] Cyclophilin J is a novel peptidyl-prolyl isomerase and target for repressing the growth of hepatocellular carcinoma.PLoS One. 2015 May 28;10(5):e0127668. doi: 10.1371/journal.pone.0127668. eCollection 2015.
• [3] Expression and Significance of Cyclophilin J in Primary Gastric Adenocarcinoma.Anticancer Res. 2017 Aug;37(8):4475-4481. doi: 10.21873/anticanres.11843.
• [4] 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.
• [5] Cyclophilin J PPIase Inhibitors Derived from 2,3-Quinoxaline-6 Amine Exhibit Antitumor Activity.Front Pharmacol. 2018 Feb 21;9:126. doi: 10.3389/fphar.2018.00126. eCollection 2018.
• [6] 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.
• [7] Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.Nat Genet. 2013 Aug;45(8):868-76. doi: 10.1038/ng.2652. Epub 2013 Jun 16.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [10] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [11] 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.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [14] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.