Details of Drug Off-Target (DOT)

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

• DOT Name: Glucoside xylosyltransferase 2 (GXYLT2)
• Synonyms: EC 2.4.2.42; Glycosyltransferase 8 domain-containing protein 4
• Gene Name: GXYLT2
• UniProt ID: GXLT2_HUMAN
• EC Number: 2.4.2.42
• Pfam ID: PF01501
• Sequence:
  MKLRSKAAALLLLALAALLLALLSLRAGRAEPPALPARPASAPQRHPAPVPARWPGPGAL
  PGASPGVRRRRPPRPRPRAGRRGAARLEKLARRPGEPRSFQAVLPPELWIHLAVVACGNR
  LEETLVMLKSAVLFSHRKIQFHIFTEDSLKPEFDKQLRQWPDSYTKKFEHRIYPITFSVG
  NPQEWKKLFKPCAAQRLFLPVILKDVDSLLYVDTDVLFLRPVDDIWKLLRLFNSTQLAAM
  APEHEIPKIGWYSRFARHPFYGSAGVNSGVMLMNLTRIRSTQFKNSMIPTGLAWEDMLYP
  LYQKYKNAITWGDQDLLNIIFYFNPECLYVFPCQWNYRPDHCMYGSNCREAEHEGVSVLH
  GNRGVYHDDKQPTFRALYEAIRDFPFQDNLFQSMYYPLQLKFLETVHTLCGRIPQVFLKQ
  IEKTMKRAYEKHVIIHVGPNQMH
• Function: Glycosyltransferase which elongates the O-linked glucose attached to EGF-like repeats in the extracellular domain of Notch proteins by catalyzing the addition of xylose.
• KEGG Pathway: Other types of O-glycan biosynthesis (hsa00514)

Molecular Interaction Atlas (MIA) of This DOT

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 Glucoside xylosyltransferase 2 (GXYLT2).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Glucoside xylosyltransferase 2 (GXYLT2).	[12]

13 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 Glucoside xylosyltransferase 2 (GXYLT2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Glucoside xylosyltransferase 2 (GXYLT2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glucoside xylosyltransferase 2 (GXYLT2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glucoside xylosyltransferase 2 (GXYLT2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Glucoside xylosyltransferase 2 (GXYLT2).	[6]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Glucoside xylosyltransferase 2 (GXYLT2).	[7]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Glucoside xylosyltransferase 2 (GXYLT2).	[8]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Glucoside xylosyltransferase 2 (GXYLT2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glucoside xylosyltransferase 2 (GXYLT2).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Glucoside xylosyltransferase 2 (GXYLT2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glucoside xylosyltransferase 2 (GXYLT2).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Glucoside xylosyltransferase 2 (GXYLT2).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Glucoside xylosyltransferase 2 (GXYLT2).	[14]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [8] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [9] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [10] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [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] 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.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.