Details of Drug Off-Target (DOT)

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

• DOT Name: Galactose-3-O-sulfotransferase 4 (GAL3ST4)
• Synonyms: Gal3ST-4; EC 2.8.2.-; Beta-galactose-3-O-sulfotransferase 4; Gal-beta-1,3-GalNAc 3'-sulfotransferase
• Gene Name: GAL3ST4
• Related Disease: Leprosy
• UniProt ID: G3ST4_HUMAN
• EC Number: 2.8.2.-
• Pfam ID: PF06990
• Sequence:
  MGPLSPARTLRLWGPRSLGVALGVFMTIGFALQLLGGPFQRRLPGLQLRQPSAPSLRPAL
  PSCPPRQRLVFLKTHKSGSSSVLSLLHRYGDQHGLRFALPARYQFGYPKLFQASRVKGYR
  PQGGGTQLPFHILCHHMRFNLKEVLQVMPSDSFFFSIVRDPAALARSAFSYYKSTSSAFR
  KSPSLAAFLANPRGFYRPGARGDHYARNLLWFDFGLPFPPEKRAKRGNIHPPRDPNPPQL
  QVLPSGAGPRAQTLNPNALIHPVSTVTDHRSQISSPASFDLGSSSFIQWGLAWLDSVFDL
  VMVAEYFDESLVLLADALCWGLDDVVGFMHNAQAGHKQGLSTVSNSGLTAEDRQLTARAR
  AWNNLDWALYVHFNRSLWARIEKYGQGRLQTAVAELRARREALAKHCLVGGEASDPKYIT
  DRRFRPFQFGSAKVLGYILRSGLSPQDQEECERLATPELQYKDKLDAKQFPPTVSLPLKT
  SRPLSP
• Function: Catalyzes the transfer of sulfate to beta-1,3-linked galactose residues in O-linked glycoproteins. Good substrates include asialofetuin, Gal-beta-1,3-GalNAc and Gal-beta-1,3 (GlcNAc-beta-1,6)GalNAc.
• Tissue Specificity: Expressed mainly in placenta, thymus, testis, ovary, spinal cord, trachea and adrenal gland and at low levels in brain, lung, spleen, prostate, small intestine, colon, stomach thyroid and lymph node.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leprosy	DISAA4UI	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Galactose-3-O-sulfotransferase 4 (GAL3ST4).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Galactose-3-O-sulfotransferase 4 (GAL3ST4).	[5]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Galactose-3-O-sulfotransferase 4 (GAL3ST4).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Galactose-3-O-sulfotransferase 4 (GAL3ST4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Galactose-3-O-sulfotransferase 4 (GAL3ST4).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Galactose-3-O-sulfotransferase 4 (GAL3ST4).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Galactose-3-O-sulfotransferase 4 (GAL3ST4).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Galactose-3-O-sulfotransferase 4 (GAL3ST4).	[9]

References

• [1] Identification of novel genetic loci GAL3ST4 and CHGB involved in susceptibility to leprosy.Sci Rep. 2017 Nov 27;7(1):16352. doi: 10.1038/s41598-017-16422-1.
• [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] 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.
• [4] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [5] 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.
• [6] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [7] 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.
• [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] 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.