Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKJ44KY)

• DOT Name: Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1)
• Gene Name: PRTFDC1
• Related Disease:
  Lesch-Nyhan syndrome
  Neoplasm
  Ovarian neoplasm
  Post-traumatic stress disorder
  Squamous cell carcinoma
  Retinitis pigmentosa
  Ovarian cancer
• UniProt ID: PRDC1_HUMAN
• PDB ID: 2JBH
• Pfam ID: PF00156
• Sequence:
  MAGSSEEAPDYGRGVVIMDDWPGYDLNLFTYPQHYYGDLEYVLIPHGIIVDRIERLAKDI
  MKDIGYSDIMVLCVLKGGYKFCADLVEHLKNISRNSDRFVSMKVDFIRLKSYRNDQSMGE
  MQIIGGDDLSTLAGKNVLIVEDVVGTGRTMKALLSNIEKYKPNMIKVASLLVKRTSRSDG
  FRPDYAGFEIPNLFVVGYALDYNEYFRDLNHICVINEHGKEKYRV
• Function: Has low, barely detectable phosphoribosyltransferase activity (in vitro). Binds GMP, IMP and alpha-D-5-phosphoribosyl 1-pyrophosphate (PRPP). Is not expected to contribute to purine metabolism or GMP salvage.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lesch-Nyhan syndrome	DISGXKU7	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Post-traumatic stress disorder	DISHL1EY	Strong	Genetic Variation	[4]
Squamous cell carcinoma	DISQVIFL	Strong	Posttranslational Modification	[2]
Retinitis pigmentosa	DISCGPY8	moderate	Biomarker	[5]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[3]

10 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 Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1).	[17]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1).	[18]

3 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 Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Phosphoribosyltransferase domain-containing protein 1 (PRTFDC1).	[14]

References

• [1] PRTFDC1 is a genetic modifier of HPRT-deficiency in the mouse.PLoS One. 2011;6(7):e22381. doi: 10.1371/journal.pone.0022381. Epub 2011 Jul 27.
• [2] PRTFDC1, a possible tumor-suppressor gene, is frequently silenced in oral squamous-cell carcinomas by aberrant promoter hypermethylation. Oncogene. 2007 Dec 13;26(57):7921-32. doi: 10.1038/sj.onc.1210589. Epub 2007 Jun 18.
• [3] Identification of PRTFDC1 silencing and aberrant promoter methylation of GPR150, ITGA8 and HOXD11 in ovarian cancers.Life Sci. 2007 Mar 27;80(16):1458-65. doi: 10.1016/j.lfs.2007.01.015. Epub 2007 Jan 20.
• [4] Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: A genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene.Psychoneuroendocrinology. 2015 Jan;51:459-71. doi: 10.1016/j.psyneuen.2014.10.017. Epub 2014 Oct 30.
• [5] Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.
• [6] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] 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.
• [9] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] 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.
• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] PRTFDC1, a possible tumor-suppressor gene, is frequently silenced in oral squamous-cell carcinomas by aberrant promoter hypermethylation. Oncogene. 2007 Dec 13;26(57):7921-32. doi: 10.1038/sj.onc.1210589. Epub 2007 Jun 18.
• [13] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [18] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.