Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIR1VDW)

• DOT Name: Phosphopentomutase (PGM2)
• Synonyms: EC 5.4.2.7; Glucose phosphomutase 2; Phosphodeoxyribomutase; Phosphoglucomutase-2; EC 5.4.2.2
• Gene Name: PGM2
• UniProt ID: PGM2_HUMAN
• EC Number: 5.4.2.2; 5.4.2.7
• Pfam ID: PF02878 ; PF02879 ; PF02880
• Sequence:
  MAAPEGSGLGEDARLDQETAQWLRWDKNSLTLEAVKRLIAEGNKEELRKCFGARMEFGTA
  GLRAAMGPGISRMNDLTIIQTTQGFCRYLEKQFSDLKQKGIVISFDARAHPSSGGSSRRF
  ARLAATTFISQGIPVYLFSDITPTPFVPFTVSHLKLCAGIMITASHNPKQDNGYKVYWDN
  GAQIISPHDKGISQAIEENLEPWPQAWDDSLIDSSPLLHNPSASINNDYFEDLKKYCFHR
  SVNRETKVKFVHTSVHGVGHSFVQSAFKAFDLVPPEAVPEQKDPDPEFPTVKYPNPEEGK
  GVLTLSFALADKTKARIVLANDPDADRLAVAEKQDSGEWRVFSGNELGALLGWWLFTSWK
  EKNQDRSALKDTYMLSSTVSSKILRAIALKEGFHFEETLTGFKWMGNRAKQLIDQGKTVL
  FAFEEAIGYMCCPFVLDKDGVSAAVISAELASFLATKNLSLSQQLKAIYVEYGYHITKAS
  YFICHDQETIKKLFENLRNYDGKNNYPKACGKFEISAIRDLTTGYDDSQPDKKAVLPTSK
  SSQMITFTFANGGVATMRTSGTEPKIKYYAELCAPPGNSDPEQLKKELNELVSAIEEHFF
  QPQKYNLQPKAD
• Function: Catalyzes the conversion of the nucleoside breakdown products ribose-1-phosphate and deoxyribose-1-phosphate to the corresponding 5-phosphopentoses. Catalyzes the interconversion of glucose-1-phosphate into glucose-6-phosphate but with a lower catalytic efficiency. In vitro, has also a low glucose 1,6-bisphosphate synthase activity which is most probably not physiologically relevant.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Pentose phosphate pathway (hsa00030)
  Galactose metabolism (hsa00052)
  Purine metabolism (hsa00230)
  Starch and sucrose metabolism (hsa00500)
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
  Biosynthesis of nucleotide sugars (hsa01250)
• Reactome Pathway:
  Pentose phosphate pathway (R-HSA-71336)
  Neutrophil degranulation (R-HSA-6798695)
• BioCyc Pathway: MetaCyc:HS09924-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Phosphopentomutase (PGM2) affects the response to substance of DTI-015.	[16]

13 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 Phosphopentomutase (PGM2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phosphopentomutase (PGM2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Phosphopentomutase (PGM2).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphopentomutase (PGM2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Phosphopentomutase (PGM2).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phosphopentomutase (PGM2).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Phosphopentomutase (PGM2).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Phosphopentomutase (PGM2).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Phosphopentomutase (PGM2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Phosphopentomutase (PGM2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Phosphopentomutase (PGM2).	[11]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Phosphopentomutase (PGM2).	[14]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Phosphopentomutase (PGM2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Phosphopentomutase (PGM2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Phosphopentomutase (PGM2).	[13]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [8] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [9] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [10] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [11] 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.
• [12] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [13] 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.
• [14] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [15] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.
• [16] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.