Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJHSY8G)

• DOT Name: Proline-rich protein 15 (PRR15)
• Gene Name: PRR15
• Related Disease:
  Colorectal carcinoma
  Digestive system neoplasm
  Neoplasm
• UniProt ID: PRR15_HUMAN
• Pfam ID: PF15321
• Sequence:
  MADSGDAGSSGPWWKSLTNSRKKSKEAAVGVPPPAQPAPGEPTPPAPPSPDWTSSSRENQ
  HPNLLGGAGEPPKPDKLYGDKSGSSRRNLKISRSGRFKEKRKVRATLLPEAGRSPEEAGF
  PGDPHEDKQ
• Function: May have a role in proliferation and/or differentiation.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Disputed	Altered Expression	[1]
Digestive system neoplasm	DISPOJCT	Disputed	Biomarker	[1]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Proline-rich protein 15 (PRR15).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Proline-rich protein 15 (PRR15).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Proline-rich protein 15 (PRR15).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Proline-rich protein 15 (PRR15).	[5]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Proline-rich protein 15 (PRR15).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Proline-rich protein 15 (PRR15).	[7]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Proline-rich protein 15 (PRR15).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Proline-rich protein 15 (PRR15).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Proline-rich protein 15 (PRR15).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Proline-rich protein 15 (PRR15).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Proline-rich protein 15 (PRR15).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Proline-rich protein 15 (PRR15).	[13]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Proline-rich protein 15 (PRR15).	[10]

References

• [1] Expression analysis of proline rich 15 (Prr15) in mouse and human gastrointestinal tumors.Mol Carcinog. 2011 Jan;50(1):8-15. doi: 10.1002/mc.20692.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] 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.
• [6] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [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] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [12] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [13] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.