Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHS1ZSP)

• DOT Name: Phosphoacetylglucosamine mutase (PGM3)
• Synonyms: PAGM; EC 5.4.2.3; Acetylglucosamine phosphomutase; N-acetylglucosamine-phosphate mutase; Phosphoglucomutase-3; PGM 3
• Gene Name: PGM3
• Related Disease: Immunodeficiency 23
• UniProt ID: AGM1_HUMAN
• EC Number: 5.4.2.3
• Pfam ID: PF21405 ; PF21404 ; PF02878 ; PF00408
• Sequence:
  MDLGAITKYSALHAKPNGLILQYGTAGFRTKAEHLDHVMFRMGLLAVLRSKQTKSTIGVM
  VTASHNPEEDNGVKLVDPLGEMLAPSWEEHATCLANAEEQDMQRVLIDISEKEAVNLQQD
  AFVVIGRDTRPSSEKLSQSVIDGVTVLGGQFHDYGLLTTPQLHYMVYCRNTGGRYGKATI
  EGYYQKLSKAFVELTKQASCSGDEYRSLKVDCANGIGALKLREMEHYFSQGLSVQLFNDG
  SKGKLNHLCGADFVKSHQKPPQGMEIKSNERCCSFDGDADRIVYYYHDADGHFHLIDGDK
  IATLISSFLKELLVEIGESLNIGVVQTAYANGSSTRYLEEVMKVPVYCTKTGVKHLHHKA
  QEFDIGVYFEANGHGTALFSTAVEMKIKQSAEQLEDKKRKAAKMLENIIDLFNQAAGDAI
  SDMLVIEAILALKGLTVQQWDALYTDLPNRQLKVQVADRRVISTTDAERQAVTPPGLQEA
  INDLVKKYKLSRAFVRPSGTEDVVRVYAEADSQESADHLAHEVSLAVFQLAGGIGERPQP
  GF
• Function: Catalyzes the conversion of GlcNAc-6-P into GlcNAc-1-P during the synthesis of uridine diphosphate/UDP-GlcNAc, a sugar nucleotide critical to multiple glycosylation pathways including protein N- and O-glycosylation.
• Tissue Specificity: Found in many tissues except lung. Relatively high expression in pancreas, heart, liver, and placenta, and relatively low expression in brain, skeletal muscle and kidney.
• KEGG Pathway:
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
  Biosynthesis of nucleotide sugars (hsa01250)
• Reactome Pathway: Synthesis of UDP-N-acetyl-glucosamine (R-HSA-446210)
• BioCyc Pathway: MetaCyc:HS00347-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency 23	DISKW4V2	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Phosphoacetylglucosamine mutase (PGM3).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Phosphoacetylglucosamine mutase (PGM3).	[15]

19 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 Phosphoacetylglucosamine mutase (PGM3).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phosphoacetylglucosamine mutase (PGM3).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Phosphoacetylglucosamine mutase (PGM3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Phosphoacetylglucosamine mutase (PGM3).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphoacetylglucosamine mutase (PGM3).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Phosphoacetylglucosamine mutase (PGM3).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Phosphoacetylglucosamine mutase (PGM3).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Phosphoacetylglucosamine mutase (PGM3).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Phosphoacetylglucosamine mutase (PGM3).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Phosphoacetylglucosamine mutase (PGM3).	[10]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Phosphoacetylglucosamine mutase (PGM3).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Phosphoacetylglucosamine mutase (PGM3).	[12]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Phosphoacetylglucosamine mutase (PGM3).	[13]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Phosphoacetylglucosamine mutase (PGM3).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Phosphoacetylglucosamine mutase (PGM3).	[16]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Phosphoacetylglucosamine mutase (PGM3).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phosphoacetylglucosamine mutase (PGM3).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Phosphoacetylglucosamine mutase (PGM3).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Phosphoacetylglucosamine mutase (PGM3).	[20]

References

• [1] PGM3 mutations cause a congenital disorder of glycosylation with severe immunodeficiency and skeletal dysplasia. Am J Hum Genet. 2014 Jul 3;95(1):96-107. doi: 10.1016/j.ajhg.2014.05.007. Epub 2014 Jun 12.
• [2] 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.
• [3] 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.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] 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.
• [7] 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.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [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] 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.
• [13] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [14] 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.
• [15] 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.
• [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] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [18] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [19] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.