Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI5MDYW)

• DOT Name: Glucoside xylosyltransferase 1 (GXYLT1)
• Synonyms: EC 2.4.2.42; Glycosyltransferase 8 domain-containing protein 3
• Gene Name: GXYLT1
• UniProt ID: GXLT1_HUMAN
• EC Number: 2.4.2.42
• Pfam ID: PF01501
• Sequence:
  MRRYLRVVVLCVACGFCSLLYAFSQLAVSLEEGTGGGGGKPQAAVASWLAGGGRGAVRGA
  GVAGPAAHPGVSDRCKDFSLCYWNPYWMLPSDVCGMNCFWEAAFRYSLKIQPVEKMHLAV
  VACGERLEETMTMLKSAIIFSIKPLQFHIFAEDQLHHSFKGRLDNWSFLQTFNYTLYPIT
  FPSENAAEWKKLFKPCASQRLFLPLILKEVDSLLYVDTDILFLRPVDDIWSLLKKFNSTQ
  IAAMAPEHEEPRIGWYNRFARHPYYGKTGVNSGVMLMNMTRMRRKYFKNDMTTVRLQWGD
  ILMPLLKKYKLNITWGDQDLLNIVFFHNPESLFVFPCQWNYRPDHCIYGSNCQEAEEGGI
  FILHGNRGVYHDDKQPAFRAVYEALRNCSFEDDNIRSLLKPLELELQKTVHTYCGKIYKI
  FIKQLAKSVRDRYARSPKEK
• 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

13 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 Glucoside xylosyltransferase 1 (GXYLT1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glucoside xylosyltransferase 1 (GXYLT1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glucoside xylosyltransferase 1 (GXYLT1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glucoside xylosyltransferase 1 (GXYLT1).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Glucoside xylosyltransferase 1 (GXYLT1).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Glucoside xylosyltransferase 1 (GXYLT1).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Glucoside xylosyltransferase 1 (GXYLT1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Glucoside xylosyltransferase 1 (GXYLT1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Glucoside xylosyltransferase 1 (GXYLT1).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Glucoside xylosyltransferase 1 (GXYLT1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Glucoside xylosyltransferase 1 (GXYLT1).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Glucoside xylosyltransferase 1 (GXYLT1).	[13]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Glucoside xylosyltransferase 1 (GXYLT1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Glucoside xylosyltransferase 1 (GXYLT1).	[8]

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] 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] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [13] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [14] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.