Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIWX5AM)

• DOT Name: Membrane progestin receptor alpha (PAQR7)
• Synonyms: mPR alpha; Membrane progesterone P4 receptor alpha; Membrane progesterone receptor alpha; Progesterone and adipoQ receptor family member 7; Progestin and adipoQ receptor family member 7; Progestin and adipoQ receptor family member VII
• Gene Name: PAQR7
• Related Disease:
  African trypanosomiasis
  Arteriosclerosis
  Atherosclerosis
  Cardiovascular disease
  Endometrial cancer
  Endometrial carcinoma
  Fatty liver disease
  Glioma
  High blood pressure
  Lung cancer
  Lung carcinoma
  Metastatic prostate carcinoma
  Neoplasm
  Osteoarthritis
  Prostate cancer
  Prostate carcinoma
  Lung adenocarcinoma
• UniProt ID: PAQR7_HUMAN
• Pfam ID: PF03006
• Sequence:
  MAMAQKLSHLLPSLRQVIQEPQLSLQPEPVFTVDRAEVPPLFWKPYIYAGYRPLHQTWRF
  YFRTLFQQHNEAVNVWTHLLAALVLLLRLALFVETVDFWGDPHALPLFIIVLASFTYLSF
  SALAHLLQAKSEFWHYSFFFLDYVGVAVYQFGSALAHFYYAIEPAWHAQVQAVFLPMAAF
  LAWLSCIGSCYNKYIQKPGLLGRTCQEVPSVLAYALDISPVVHRIFVSSDPTTDDPALLY
  HKCQVVFFLLAAAFFSTFMPERWFPGSCHVFGQGHQLFHIFLVLCTLAQLEAVALDYEAR
  RPIYEPLHTHWPHNFSGLFLLTVGSSILTAFLLSQLVQRKLDQKTK
• 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. Involved in neurosteroid inhibition of apoptosis. Also binds dehydroepiandrosterone (DHEA), pregnanolone, pregnenolone and allopregnanolone.
• Tissue Specificity: Expressed in a wide range of tissues including ovary, testis, placenta, uterus and bladder.
• KEGG Pathway: Chemical carcinogenesis - receptor activation (hsa05207)

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
African trypanosomiasis	DISBIXK4	Strong	Altered Expression	[1]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[2]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[2]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[3]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[4]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[4]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Altered Expression	[6]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[7]
Lung cancer	DISCM4YA	Strong	Biomarker	[8]
Lung carcinoma	DISTR26C	Strong	Biomarker	[8]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Genetic Variation	[9]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Osteoarthritis	DIS05URM	Strong	Biomarker	[10]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[11]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[11]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Membrane progestin receptor alpha (PAQR7).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Membrane progestin receptor alpha (PAQR7).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Membrane progestin receptor alpha (PAQR7).	[15]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Membrane progestin receptor alpha (PAQR7).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Membrane progestin receptor alpha (PAQR7).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Membrane progestin receptor alpha (PAQR7).	[19]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of Membrane progestin receptor alpha (PAQR7).	[20]

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 affects the methylation of Membrane progestin receptor alpha (PAQR7).	[17]

References

• [1] The role of Trypanosoma brucei MRPA in melarsoprol susceptibility.Mol Biochem Parasitol. 2006 Mar;146(1):38-44. doi: 10.1016/j.molbiopara.2005.10.016. Epub 2005 Nov 18.
• [2] Scavenger receptor deficiency leads to more complex atherosclerotic lesions in APOE3Leiden transgenic mice.Atherosclerosis. 1999 Jun;144(2):315-21. doi: 10.1016/s0021-9150(98)00332-3.
• [3] A CBS haplotype and a polymorphism at the MSR gene are associated with cardiovascular disease in a Spanish case-control study.Clin Biochem. 2007 Aug;40(12):864-8. doi: 10.1016/j.clinbiochem.2007.04.008. Epub 2007 Apr 27.
• [4] 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.
• [5] Grading fatty liver by ultrasound time-domain radiofrequency signal analysis: an in vivo study of rats.Exp Anim. 2018 May 10;67(2):249-257. doi: 10.1538/expanim.17-0124. Epub 2018 Jan 12.
• [6] Expression of Progesterone Receptor Membrane Component 1 (PGRMC1), Progestin and AdipoQ Receptor 7 (PAQPR7), and Plasminogen Activator Inhibitor 1 RNA-Binding Protein (PAIRBP1) in Glioma Spheroids In Vitro.Biomed Res Int. 2016;2016:8065830. doi: 10.1155/2016/8065830. Epub 2016 Jun 1.
• [7] Folate nutritional genetics and risk for hypertension in an elderly population sample.J Nutrigenet Nutrigenomics. 2009;2(1):1-8. doi: 10.1159/000160079. Epub 2008 Oct 8.
• [8] Progesterone inhibits the migration and invasion of A549 lung cancer cells through membrane progesterone receptor -mediated mechanisms.Oncol Rep. 2013 May;29(5):1873-80. doi: 10.3892/or.2013.2336. Epub 2013 Mar 6.
• [9] High-resolution physical map and transcript identification of a prostate cancer deletion interval on 8p22.Genome Res. 2000 Feb;10(2):244-57. doi: 10.1101/gr.10.2.244.
• [10] Emerging Roles of circRNA Related to the Mechanical Stress in Human Cartilage Degradation of Osteoarthritis.Mol Ther Nucleic Acids. 2017 Jun 16;7:223-230. doi: 10.1016/j.omtn.2017.04.004. Epub 2017 Apr 12.
• [11] Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer.Cancer Res. 1993 Sep 1;53(17):3869-73.
• [12] mPR mediates P4/Org OD02-0 to improve the sensitivity of lung adenocarcinoma to EGFR-TKIs via the EGFR-SRC-ERK1/2 pathway.Mol Carcinog. 2020 Feb;59(2):179-192. doi: 10.1002/mc.23139. Epub 2019 Nov 28.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [15] 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.
• [16] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [17] 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.
• [18] 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.
• [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] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.