Details of Drug Off-Target (DOT)

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

• DOT Name: Membrane progestin receptor gamma (PAQR5)
• Synonyms: mPR gamma; Membrane progesterone P4 receptor gamma; Membrane progesterone receptor gamma; Progesterone and adipoQ receptor family member 5; Progestin and adipoQ receptor family member 5; Progestin and adipoQ receptor family member V
• Gene Name: PAQR5
• Related Disease:
  Cardiovascular disease
  Endometrial cancer
  Endometrial carcinoma
• UniProt ID: PAQR5_HUMAN
• Pfam ID: PF03006
• Sequence:
  MLSLKLPRLFSIDQIPQVFHEQGILFGYRHPQSSATACILSLFQMTNETLNIWTHLLPFW
  FFAWRFVTALYMTDIKNDSYSWPMLVYMCTSCVYPLVSSCAHTFSSMSKNARHICYFLDY
  GAVNLFSLGSAIAYSAYTFPDALMCTTFHDYYVALAVLNTILSTGLSCYSRFLEIQKPRL
  CKVIRVLAFAYPYTWDSLPIFYRLFLFPGESAQNEATSYHQKHMIMTLLASFLYSAHLPE
  RLAPGRFDYIGHSHQLFHVCVILATHMQMEAILLDKTLRKEWLLATSKPFSFSQIAGAIL
  LCIIFSLSNIIYFSAALYRIPKPELHKKET
• Function: Plasma membrane progesterone (P4) receptor coupled to G proteins. Seems to act through a G(i) mediated pathway. May be involved in oocyte maturation.
• Tissue Specificity: Expressed in the brain, lung, kidney, colon, adrenal and lung.
• KEGG Pathway: Chemical carcinogenesis - receptor activation (hsa05207)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[1]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[2]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[2]

3 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 Membrane progestin receptor gamma (PAQR5).	[3]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Membrane progestin receptor gamma (PAQR5).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Membrane progestin receptor gamma (PAQR5).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Membrane progestin receptor gamma (PAQR5).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Membrane progestin receptor gamma (PAQR5).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Membrane progestin receptor gamma (PAQR5).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Membrane progestin receptor gamma (PAQR5).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Membrane progestin receptor gamma (PAQR5).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Membrane progestin receptor gamma (PAQR5).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Membrane progestin receptor gamma (PAQR5).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Membrane progestin receptor gamma (PAQR5).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Membrane progestin receptor gamma (PAQR5).	[12]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Membrane progestin receptor gamma (PAQR5).	[13]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Membrane progestin receptor gamma (PAQR5).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Membrane progestin receptor gamma (PAQR5).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Membrane progestin receptor gamma (PAQR5).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Membrane progestin receptor gamma (PAQR5).	[4]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Membrane progestin receptor gamma (PAQR5).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Membrane progestin receptor gamma (PAQR5).	[19]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Membrane progestin receptor gamma (PAQR5).	[20]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] Membrane progesterone receptors and have potential as prognostic biomarkers of endometrial cancer.J Steroid Biochem Mol Biol. 2018 Apr;178:303-311. doi: 10.1016/j.jsbmb.2018.01.011. Epub 2018 Jan 17.
• [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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [13] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [15] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] 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.
• [18] 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.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.