Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7UPL4D)

• DOT Name: Galactose mutarotase (GALM)
• Synonyms: EC 5.1.3.3; Aldose 1-epimerase
• Gene Name: GALM
• Related Disease: Galactosemia 4
• UniProt ID: GALM_HUMAN
• PDB ID: 1SNZ; 1SO0
• EC Number: 5.1.3.3
• Pfam ID: PF01263
• Sequence:
  MASVTRAVFGELPSGGGTVEKFQLQSDLLRVDIISWGCTITALEVKDRQGRASDVVLGFA
  ELEGYLQKQPYFGAVIGRVANRIAKGTFKVDGKEYHLAINKEPNSLHGGVRGFDKVLWTP
  RVLSNGVQFSRISPDGEEGYPGELKVWVTYTLDGGELIVNYRAQASQATPVNLTNHSYFN
  LAGQASPNINDHEVTIEADTYLPVDETLIPTGEVAPVQGTAFDLRKPVELGKHLQDFHLN
  GFDHNFCLKGSKEKHFCARVHHAASGRVLEVYTTQPGVQFYTGNFLDGTLKGKNGAVYPK
  HSGFCLETQNWPDAVNQPRFPPVLLRPGEEYDHTTWFKFSVA
• Function: Mutarotase that catalyzes the interconversion of beta-D-galactose and alpha-D-galactose during galactose metabolism. Beta-D-galactose is metabolized in the liver into glucose 1-phosphate, the primary metabolic fuel, by the action of four enzymes that constitute the Leloir pathway: GALM, GALK1 (galactokinase), GALT (galactose-1-phosphate uridylyltransferase) and GALE (UDP-galactose-4'-epimerase). Involved in the maintenance of the equilibrium between the beta- and alpha-anomers of galactose, therefore ensuring a sufficient supply of the alpha-anomer for GALK1. Also active on D-glucose although shows a preference for galactose over glucose.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Galactose metabolism (hsa00052)
  Metabolic pathways (hsa01100)
• BioCyc Pathway: MetaCyc:HS07125-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
Galactosemia 4	DISHL9R0	Strong	Autosomal recessive	[1]

18 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 Galactose mutarotase (GALM).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Galactose mutarotase (GALM).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Galactose mutarotase (GALM).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Galactose mutarotase (GALM).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Galactose mutarotase (GALM).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Galactose mutarotase (GALM).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Galactose mutarotase (GALM).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Galactose mutarotase (GALM).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Galactose mutarotase (GALM).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Galactose mutarotase (GALM).	[10]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Galactose mutarotase (GALM).	[9]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Galactose mutarotase (GALM).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of Galactose mutarotase (GALM).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Galactose mutarotase (GALM).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Galactose mutarotase (GALM).	[15]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Galactose mutarotase (GALM).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Galactose mutarotase (GALM).	[17]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Galactose mutarotase (GALM).	[18]

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 decreases the methylation of Galactose mutarotase (GALM).	[13]

References

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• [3] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
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• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] 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.
• [10] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [11] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [12] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Galactomutarotase and other galactose-related genes are rapidly induced by retinoic acid in human myeloid cells. Biochemistry. 2007 Dec 25;46(51):15198-207. doi: 10.1021/bi701891t. Epub 2007 Dec 4.
• [17] 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.
• [18] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.