Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMH6OWG)

• DOT Name: Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1)
• Synonyms: Proline-rich gamma-carboxyglutamic acid protein 1; Proline-rich Gla protein 1
• Gene Name: PRRG1
• UniProt ID: TMG1_HUMAN
• Pfam ID: PF00594
• Sequence:
  MGRVFLTGEKANSILKRYPRANGFFEEIRQGNIERECKEEFCTFEEAREAFENNEKTKEF
  WSTYTKAQQGESNRGSDWFQFYLTFPLIFGLFIILLVIFLIWRCFLRNKTRRQTVTEGHI
  PFPQHLNIITPPPPPDEVFDSSGLSPGFLGYVVGRSDSVSTRLSNCDPPPTYEEATGQVN
  LQRSETEPHLDPPPEYEDIVNSNSASAIPMVPVVTTIK
• Tissue Specificity: Highly expressed in the spinal cord.

Molecular Interaction Atlas (MIA) of This DOT

16 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 Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[7]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[15]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane gamma-carboxyglutamic acid protein 1 (PRRG1).	[11]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [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] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [9] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [16] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.