Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHR35JF)

• DOT Name: N-acetylgalactosamine kinase (GALK2)
• Synonyms: EC 2.7.1.157; GalNAc kinase; Galactokinase 2
• Gene Name: GALK2
• Related Disease:
  Dental caries
  Lung adenocarcinoma
  Lung carcinoma
• UniProt ID: GALK2_HUMAN
• PDB ID: 2A2C; 2A2D
• EC Number: 2.7.1.157
• Pfam ID: PF10509 ; PF08544 ; PF00288
• Sequence:
  MATESPATRRVQVAEHPRLLKLKEMFNSKFGSIPKFYVRAPGRVNIIGEHIDYCGYSVLP
  MAVEQDVLIAVEPVKTYALQLANTNPLYPDFSTSANNIQIDKTKPLWHNYFLCGLKGIQE
  HFGLSNLTGMNCLVDGNIPPSSGLSSSSALVCCAGLVTLTVLGRNLSKVELAEICAKSER
  YIGTEGGGMDQSISFLAEEGTAKLIEFSPLRATDVKLPSGAVFVIANSCVEMNKAATSHF
  NIRVMECRLAAKLLAKYKSLQWDKVLRLEEVQAKLGISLEEMLLVTEDALHPEPYNPEEI
  CRCLGISLEELRTQILSPNTQDVLIFKLYQRAKHVYSEAARVLQFKKICEEAPENMVQLL
  GELMNQSHMSCRDMYECSCPELDQLVDICRKFGAQGSRLTGAGWGGCTVSMVPADKLPSF
  LANVHKAYYQRSDGSLAPEKQSLFATKPGGGALVLLEA
• Function: Acts on GalNAc. Also acts as a galactokinase when galactose is present at high concentrations. May be involved in a salvage pathway for the reutilization of free GalNAc derived from the degradation of complex carbohydrates.
• KEGG Pathway:
  Amino sugar and nucleotide sugar metabolism (hsa00520)
  Metabolic pathways (hsa01100)
  Biosynthesis of nucleotide sugars (hsa01250)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dental caries	DISRBCMD	Limited	Biomarker	[1]
Lung adenocarcinoma	DISD51WR	Limited	Genetic Variation	[2]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[2]

3 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 N-acetylgalactosamine kinase (GALK2).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of N-acetylgalactosamine kinase (GALK2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of N-acetylgalactosamine kinase (GALK2).	[10]

9 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 N-acetylgalactosamine kinase (GALK2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of N-acetylgalactosamine kinase (GALK2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of N-acetylgalactosamine kinase (GALK2).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of N-acetylgalactosamine kinase (GALK2).	[8]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of N-acetylgalactosamine kinase (GALK2).	[9]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of N-acetylgalactosamine kinase (GALK2).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of N-acetylgalactosamine kinase (GALK2).	[11]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of N-acetylgalactosamine kinase (GALK2).	[12]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of N-acetylgalactosamine kinase (GALK2).	[13]

References

• [1] Human genes influence the interaction between Streptococcus mutans and host caries susceptibility: a genome-wide association study in children with primary dentition.Int J Oral Sci. 2019 May 30;11(2):19. doi: 10.1038/s41368-019-0051-4.
• [2] Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
• [3] 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.
• [4] 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.
• [5] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [9] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [10] 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.
• [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] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [13] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.