Details of Drug Off-Target (DOT)

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

• DOT Name: GMP reductase 2 (GMPR2)
• Synonyms: GMPR 2; EC 1.7.1.7; Guanosine 5'-monophosphate oxidoreductase 2; Guanosine monophosphate reductase 2
• Gene Name: GMPR2
• Related Disease:
  Adenocarcinoma
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Leukemia
  Breast cancer
  Breast carcinoma
  Neoplasm
• UniProt ID: GMPR2_HUMAN
• PDB ID: 2A7R; 2BZN; 2C6Q
• EC Number: 1.7.1.7
• Pfam ID: PF00478
• Sequence:
  MPHIDNDVKLDFKDVLLRPKRSTLKSRSEVDLTRSFSFRNSKQTYSGVPIIAANMDTVGT
  FEMAKVLCKFSLFTAVHKHYSLVQWQEFAGQNPDCLEHLAASSGTGSSDFEQLEQILEAI
  PQVKYICLDVANGYSEHFVEFVKDVRKRFPQHTIMAGNVVTGEMVEELILSGADIIKVGI
  GPGSVCTTRKKTGVGYPQLSAVMECADAAHGLKGHIISDGGCSCPGDVAKAFGAGADFVM
  LGGMLAGHSESGGELIERDGKKYKLFYGMSSEMAMKKYAGGVAEYRASEGKTVEVPFKGD
  VEHTIRDILGGIRSTCTYVGAAKLKELSRRTTFIRVTQQVNPIFSEAC
• Function: Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides. Plays a role in modulating cellular differentiation.
• Tissue Specificity: Highly expressed in heart, skeletal muscle, kidney, brain, liver, prostate, spleen, placenta, testis and ovary. Low expression in colon, thymus and peripheral blood leukocytes.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
• Reactome Pathway: Purine salvage (R-HSA-74217)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Biomarker	[1]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[1]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[1]
Leukemia	DISNAKFL	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[3]
Neoplasm	DISZKGEW	Limited	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of GMP reductase 2 (GMPR2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of GMP reductase 2 (GMPR2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GMP reductase 2 (GMPR2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of GMP reductase 2 (GMPR2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of GMP reductase 2 (GMPR2).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of GMP reductase 2 (GMPR2).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of GMP reductase 2 (GMPR2).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of GMP reductase 2 (GMPR2).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of GMP reductase 2 (GMPR2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of GMP reductase 2 (GMPR2).	[13]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of GMP reductase 2 (GMPR2).	[14]

References

• [1] Diverse proteomic alterations in gastric adenocarcinoma.Proteomics. 2004 Oct;4(10):3276-87. doi: 10.1002/pmic.200300916.
• [2] Cloning and functional characterization of GMPR2, a novel human guanosine monophosphate reductase, which promotes the monocytic differentiation of HL-60 leukemia cells.J Cancer Res Clin Oncol. 2003 Feb;129(2):76-83. doi: 10.1007/s00432-002-0413-7. Epub 2003 Mar 1.
• [3] Lack of expression of the proteins GMPR2 and PPAR are associated with the basal phenotype and patient outcome in breast cancer.Breast Cancer Res Treat. 2013 Jan;137(1):127-37. doi: 10.1007/s10549-012-2302-3. Epub 2012 Dec 4.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [13] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [14] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.