Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT17ST61)

• DOT Name: 2-hydroxyacylsphingosine 1-beta-galactosyltransferase
• Synonyms: EC 2.4.1.47; Ceramide UDP-galactosyltransferase; Cerebroside synthase; UDP-galactose-ceramide galactosyltransferase
• Gene Name: UGT8
• UniProt ID: CGT_HUMAN
• EC Number: 2.4.1.47
• Pfam ID: PF00201
• Sequence:
  MKSYTPYFILLWSAVGIAKAAKIIIVPPIMFESHMYIFKTLASALHERGHHTVFLLSEGR
  DIAPSNHYSLQRYPGIFNSTTSDAFLQSKMRNIFSGRLTAIELFDILDHYTKNCDLMVGN
  HALIQGLKKEKFDLLLVDPNDMCGFVIAHLLGVKYAVFSTGLWYPAEVGAPAPLAYVPEF
  NSLLTDRMNLLQRMKNTGVYLISRLGVSFLVLPKYERIMQKYNLLPEKSMYDLVHGSSLW
  MLCTDVALEFPRPTLPNVVYVGGILTKPASPLPEDLQRWVNGANEHGFVLVSFGAGVKYL
  SEDIANKLAGALGRLPQKVIWRFSGPKPKNLGNNTKLIEWLPQNDLLGHSKIKAFLSHGG
  LNSIFETIYHGVPVVGIPLFGDHYDTMTRVQAKGMGILLEWKTVTEKELYEALVKVINNP
  SYRQRAQKLSEIHKDQPGHPVNRTIYWIDYIIRHNGAHHLRAAVHQISFCQYFLLDIAFV
  LLLGAALLYFLLSWVTKFIYRKIKSLWSRNKHSTVNGHYHNGILNGKYKRNGHIKHEKKV
  K
• Function: Catalyzes the transfer of galactose to ceramide, a key enzymatic step in the biosynthesis of galactocerebrosides, which are abundant sphingolipids of the myelin membrane of the central nervous system and peripheral nervous system. Galactosylates both hydroxy- and non-hydroxy fatty acid-containing ceramides and diglycerides.
• KEGG Pathway:
  Ether lipid metabolism (hsa00565)
  Sphingolipid metabolism (hsa00600)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Glycosphingolipid biosynthesis (R-HSA-9840309)
• BioCyc Pathway: MetaCyc:HS10812-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

14 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 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[7]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[8]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[10]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of 2-hydroxyacylsphingosine 1-beta-galactosyltransferase.	[11]

References

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• [2] 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.
• [3] 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.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [8] 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.
• [9] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] 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.
• [12] 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.
• [13] 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.