Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6J9UKK)

• DOT Name: Proline-rich protein 15-like protein (PRR15L)
• Synonyms: Protein ATAD4
• Gene Name: PRR15L
• Related Disease:
  Adenocarcinoma
  Advanced cancer
• UniProt ID: PR15L_HUMAN
• Pfam ID: PF15321
• Sequence:
  MTTEIGWWKLTFLRKKKSTPKVLYEIPDTYAQTEGDAEPPRPDAGGPNSDFNTRLEKIVD
  KSTKGKHVKVSNSGRFKEKKKVRATLAENPNLFDDHEEGRSSK

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]

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 Proline-rich protein 15-like protein (PRR15L).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Proline-rich protein 15-like protein (PRR15L).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Proline-rich protein 15-like protein (PRR15L).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Proline-rich protein 15-like protein (PRR15L).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Proline-rich protein 15-like protein (PRR15L).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Proline-rich protein 15-like protein (PRR15L).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Proline-rich protein 15-like protein (PRR15L).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Proline-rich protein 15-like protein (PRR15L).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Proline-rich protein 15-like protein (PRR15L).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Proline-rich protein 15-like protein (PRR15L).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Proline-rich protein 15-like protein (PRR15L).	[13]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Proline-rich protein 15-like protein (PRR15L).	[14]

References

• [1] Identification of a novel PRR15L-RSPO2 fusion transcript in a sigmoid colon cancer derived from superficially serrated adenoma.Virchows Arch. 2019 Nov;475(5):659-663. doi: 10.1007/s00428-019-02604-x. Epub 2019 Jun 17.
• [2] Reprogramming of the transcriptome in a novel chromosome 3 transfer tumor suppressor ovarian cancer cell line model affected molecular networks that are characteristic of ovarian cancer.Mol Carcinog. 2009 Jul;48(7):648-61. doi: 10.1002/mc.20511.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [14] An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat. Toxicol In Vitro. 2022 Jun;81:105333. doi: 10.1016/j.tiv.2022.105333. Epub 2022 Feb 16.