Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT26I382)

• DOT Name: Proline-rich protein 4 (PRR4)
• Synonyms: Lacrimal proline-rich protein; Nasopharyngeal carcinoma-associated proline-rich protein 4
• Gene Name: PRR4
• Related Disease:
  Pseudotumor cerebri
  Keratoconjunctivitis sicca
• UniProt ID: PROL4_HUMAN
• Pfam ID: PF15240
• Sequence:
  MLLVLLSVVLLALSSAQSTDNDVNYEDFTFTIPDVEDSSQRPDQGPQRPPPEGLLPRPPG
  DSGNQDDGPQQRPPKPGGHHRHPPPPPFQNQQRPPRRGHRQLSLPRFPSVSLQEASSFFQ
  RDRPARHPQEQPLW
• Tissue Specificity: Abundantly expressed in lacrimal gland where it is found in the acinar cells but not in the intralobular ducts. Also found in the submandibular gland, the parotid and sublingual glands.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pseudotumor cerebri	DISLLY7S	Definitive	Genetic Variation	[1]
Keratoconjunctivitis sicca	DISNOENH	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Proline-rich protein 4 (PRR4).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Proline-rich protein 4 (PRR4).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Proline-rich protein 4 (PRR4).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Proline-rich protein 4 (PRR4).	[5]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Proline-rich protein 4 (PRR4).	[7]

References

• [1] Genetic Survey of Adult-Onset Idiopathic Intracranial Hypertension.J Neuroophthalmol. 2019 Mar;39(1):50-55. doi: 10.1097/WNO.0000000000000648.
• [2] Lacrimal proline rich 4 (LPRR4) protein in the tear fluid is a potential biomarker of dry eye syndrome.PLoS One. 2012;7(12):e51979. doi: 10.1371/journal.pone.0051979. Epub 2012 Dec 18.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.