Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBM8F2U)

• DOT Name: Beta-1,4-galactosyltransferase 6 (B4GALT6)
• Synonyms: Beta-1,4-GalTase 6; Beta4Gal-T6; b4Gal-T6; EC 2.4.1.-; Glucosylceramide beta-1,4-galactosyltransferase; EC 2.4.1.274; Lactosylceramide synthase; LacCer synthase; UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 6; UDP-Gal:glucosylceramide beta-1,4-galactosyltransferase; UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 6
• Gene Name: B4GALT6
• Related Disease:
  Colorectal carcinoma
  Multiple sclerosis
• UniProt ID: B4GT6_HUMAN
• EC Number: 2.4.1.-; 2.4.1.274
• Pfam ID: PF02709 ; PF13733
• Sequence:
  MSVLRRMMRVSNRSLLAFIFFFSLSSSCLYFIYVAPGIANTYLFMVQARGIMLRENVKTI
  GHMIRLYTNKNSTLNGTDYPEGNNSSDYLVQTTTYLPENFTYSPYLPCPEKLPYMRGFLN
  VNVSEVSFDEIHQLFSKDLDIEPGGHWRPKDCKPRWKVAVLIPFRNRHEHLPIFFLHLIP
  MLQKQRLEFAFYVIEQTGTQPFNRAMLFNVGFKEAMKDSVWDCVIFHDVDHLPENDRNYY
  GCGEMPRHFAAKLDKYMYILPYKEFFGGVSGLTVEQFRKINGFPNAFWGWGGEDDDLWNR
  VHYAGYNVTRPEGDLGKYKSIPHHHRGEVQFLGRYKLLRYSKERQYIDGLNNLIYRPKIL
  VDRLYTNISVNLMPELAPIEDY
• Function: Catalyzes the synthesis of lactosylceramide (LacCer) via the transfer of galactose from UDP-galactose to glucosylceramide (GlcCer). LacCer is the starting point in the biosynthesis of all gangliosides (membrane-bound glycosphingolipids) which play pivotal roles in the CNS including neuronal maturation and axonal and myelin formation.
• Tissue Specificity: High expression in brain and adrenal gland, lower in liver, lung, colon and peripheral white blood cells.
• KEGG Pathway:
  Sphingolipid metabolism (hsa00600)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  O-linked glycosylation of mucins (R-HSA-913709)
  N-Glycan antennae elongation (R-HSA-975577)
  Keratan sulfate biosynthesis (R-HSA-2022854)
• BioCyc Pathway: MetaCyc:ENSG00000118276-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[2]

8 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 Beta-1,4-galactosyltransferase 6 (B4GALT6).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Beta-1,4-galactosyltransferase 6 (B4GALT6).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Beta-1,4-galactosyltransferase 6 (B4GALT6).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Beta-1,4-galactosyltransferase 6 (B4GALT6).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Beta-1,4-galactosyltransferase 6 (B4GALT6).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Beta-1,4-galactosyltransferase 6 (B4GALT6).	[8]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Beta-1,4-galactosyltransferase 6 (B4GALT6).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Beta-1,4-galactosyltransferase 6 (B4GALT6).	[10]

References

• [1] Lactosylceramide synthase -1,4-GalT-V: A novel target for the diagnosis and therapy of human colorectal cancer.Biochem Biophys Res Commun. 2019 Jan 8;508(2):380-386. doi: 10.1016/j.bbrc.2018.11.149. Epub 2018 Nov 28.
• [2] Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation.Nat Med. 2014 Oct;20(10):1147-56. doi: 10.1038/nm.3681. Epub 2014 Sep 14.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] 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.
• [7] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.
• [10] 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.