Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNSM9XP)

• DOT Name: Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 (B3GAT2)
• Synonyms: EC 2.4.1.135; Beta-1,3-glucuronyltransferase 2; GlcAT-D; UDP-glucuronosyltransferase S; GlcAT-S; Glucuronosyltransferase S
• Gene Name: B3GAT2
• Related Disease:
  Barrett esophagus
  Schizophrenia
  Venous thromboembolism
• UniProt ID: B3GA2_HUMAN
• PDB ID: 2D0J
• EC Number: 2.4.1.135
• Pfam ID: PF03360
• Sequence:
  MKSALFTRFFILLPWILIVIIMLDVDTRRPVPPLTPRPYFSPYAVGRGGARLPLRRGGPA
  HGTQKRNQSRPQPQPEPQLPTIYAITPTYSRPVQKAELTRLANTFRQVAQLHWILVEDAA
  ARSELVSRFLARAGLPSTHLHVPTPRRYKRPGLPRATEQRNAGLAWLRQRHQHQRAQPGV
  LFFADDDNTYSLELFQEMRTTRKVSVWPVGLVGGRRYERPLVENGKVVGWYTGWRADRPF
  AIDMAGFAVSLQVILSNPKAVFKRRGSQPGMQESDFLKQITTVEELEPKANNCTKVLVWH
  TRTEKVNLANEPKYHLDTVKIEV
• Function: Involved in the biosynthesis of L2/HNK-1 carbohydrate epitope on both glycolipids and glycoproteins.
• Tissue Specificity: Expressed in the trachea, retina, spinal cord, hippocampus and other brain regions, and, at lower levels, in testis and ovary.
• KEGG Pathway:
  Mannose type O-glycan biosynthesis (hsa00515)
  Metabolic pathways (hsa01100)
• Reactome Pathway: A tetrasaccharide linker sequence is required for GAG synthesis (R-HSA-1971475)
• BioCyc Pathway: MetaCyc:HS03557-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Barrett esophagus	DIS416Y7	Strong	Posttranslational Modification	[1]
Schizophrenia	DISSRV2N	Strong	Biomarker	[2]
Venous thromboembolism	DISUR7CR	moderate	Genetic Variation	[3]

6 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 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 (B3GAT2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 (B3GAT2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 (B3GAT2).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 (B3GAT2).	[8]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 (B3GAT2).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 (B3GAT2).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 (B3GAT2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 2 (B3GAT2).	[10]

References

• [1] Methylated B3GAT2 and ZNF793 Are Potential Detection Biomarkers for Barrett's Esophagus.Cancer Epidemiol Biomarkers Prev. 2015 Dec;24(12):1890-7. doi: 10.1158/1055-9965.EPI-15-0370. Epub 2015 Nov 6.
• [2] Candidate gene analysis of the human natural killer-1 carbohydrate pathway and perineuronal nets in schizophrenia: B3GAT2 is associated with disease risk and cortical surface area.Biol Psychiatry. 2011 Jan 1;69(1):90-6. doi: 10.1016/j.biopsych.2010.07.035. Epub 2010 Oct 15.
• [3] Rare genetic variants in SMAP1, B3GAT2, and RIMS1 contribute to pediatric venous thromboembolism.Blood. 2017 Feb 9;129(6):783-790. doi: 10.1182/blood-2016-07-728840. Epub 2016 Dec 23.
• [4] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [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.