Details of Drug Off-Target (DOT)

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

• DOT Name: Beta-1,3-galactosyltransferase 5 (B3GALT5)
• Synonyms: Beta-1,3-GalTase 5; Beta3Gal-T5; Beta3GalT5; b3Gal-T5; EC 2.4.1.-; Beta-3-Gx-T5; UDP-Gal:beta-GlcNAc beta-1,3-galactosyltransferase 5; UDP-galactose:beta-N-acetylglucosamine beta-1,3-galactosyltransferase 5
• Gene Name: B3GALT5
• Related Disease:
  Adenocarcinoma
  Hepatocellular carcinoma
  Acute myelogenous leukaemia
  Colon cancer
  Colon carcinoma
  Pancreatic cancer
• UniProt ID: B3GT5_HUMAN
• EC Number: 2.4.1.-
• Pfam ID: PF01762
• Sequence:
  MAFPKMRLMYICLLVLGALCLYFSMYSLNPFKEQSFVYKKDGNFLKLPDTDCRQTPPFLV
  LLVTSSHKQLAERMAIRQTWGKERMVKGKQLKTFFLLGTTSSAAETKEVDQESQRHGDII
  QKDFLDVYYNLTLKTMMGIEWVHRFCPQAAFVMKTDSDMFINVDYLTELLLKKNRTTRFF
  TGFLKLNEFPIRQPFSKWFVSKSEYPWDRYPPFCSGTGYVFSGDVASQVYNVSKSVPYIK
  LEDVFVGLCLERLNIRLEELHSQPTFFPGGLRFSVCLFRRIVACHFIKPRTLLDYWQALE
  NSRGEDCPPV
• Function: Catalyzes the transfer of Gal to GlcNAc-based acceptors with a preference for the core3 O-linked glycan GlcNAc(beta1,3)GalNAc structure. Can use glycolipid LC3Cer as an efficient acceptor.
• Tissue Specificity: Expressed in stomach, jejunum, colon, pancreas, small intestine, testis and gastrointestinal and pancreatic cancer cell lines. Hardly detected in lung, liver, adrenal gland and peripheral blood leukocytes.
• KEGG Pathway:
  Glycosphingolipid biosynthesis - lacto and neolacto series (hsa00601)
  Glycosphingolipid biosynthesis - globo and isoglobo series (hsa00603)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Lewis blood group biosynthesis (R-HSA-9037629)
• BioCyc Pathway: MetaCyc:MONOMER-20081

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[2]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[3]
Colon cancer	DISVC52G	Limited	Posttranslational Modification	[4]
Colon carcinoma	DISJYKUO	Limited	Posttranslational Modification	[4]
Pancreatic cancer	DISJC981	Limited	Posttranslational Modification	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Beta-1,3-galactosyltransferase 5 (B3GALT5).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Beta-1,3-galactosyltransferase 5 (B3GALT5).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Beta-1,3-galactosyltransferase 5 (B3GALT5).	[11]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Beta-1,3-galactosyltransferase 5 (B3GALT5).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Beta-1,3-galactosyltransferase 5 (B3GALT5).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Beta-1,3-galactosyltransferase 5 (B3GALT5).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Beta-1,3-galactosyltransferase 5 (B3GALT5).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Beta-1,3-galactosyltransferase 5 (B3GALT5).	[12]
Kaempferol	DMHEMUB	Investigative	Kaempferol decreases the expression of Beta-1,3-galactosyltransferase 5 (B3GALT5).	[13]
Apigenin	DMI3491	Investigative	Apigenin increases the expression of Beta-1,3-galactosyltransferase 5 (B3GALT5).	[13]

References

• [1] beta 1,3-Galactosyltransferase beta 3Gal-T5 acts on the GlcNAcbeta 1-->3Galbeta 1-->4GlcNAcbeta 1-->R sugar chains of carcinoembryonic antigen and other N-linked glycoproteins and is down-regulated in colon adenocarcinomas.J Biol Chem. 2001 Feb 2;276(5):3564-73. doi: 10.1074/jbc.M006662200. Epub 2000 Oct 31.
• [2] High expression FUT1 and B3GALT5 is an independent predictor of postoperative recurrence and survival in hepatocellular carcinoma.Sci Rep. 2017 Sep 7;7(1):10750. doi: 10.1038/s41598-017-11136-w.
• [3] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [4] Unexpected distribution of CA19.9 and other type 1 chain Lewis antigens in normal and cancer tissues of colon and pancreas: Importance of the detection method and role of glycosyltransferase regulation.Biochim Biophys Acta Gen Subj. 2017 Jan;1861(1 Pt A):3210-3220. doi: 10.1016/j.bbagen.2016.08.005. Epub 2016 Aug 14.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Association of Arsenic Exposure with Whole Blood DNA Methylation: An Epigenome-Wide Study of Bangladeshi Adults. Environ Health Perspect. 2019 May;127(5):57011. doi: 10.1289/EHP3849. Epub 2019 May 28.
• [9] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [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] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [13] Differential responses to retinoic acid and endocrine disruptor compounds of subpopulations within human embryonic stem cell lines. Differentiation. 2012 Nov;84(4):330-43. doi: 10.1016/j.diff.2012.07.006. Epub 2012 Aug 18.