Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI5SX62)

• DOT Name: Beta-1,4-galactosyltransferase 4 (B4GALT4)
• Synonyms: Beta-1,4-GalTase 4; Beta4Gal-T4; b4Gal-T4; EC 2.4.1.-; Beta-N-acetylglucosaminyl-glycolipid beta-1,4-galactosyltransferase; Lactotriaosylceramide beta-1,4-galactosyltransferase; EC 2.4.1.275; N-acetyllactosamine synthase; EC 2.4.1.90; Nal synthase; UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 4; UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 4
• Gene Name: B4GALT4
• Related Disease:
  Prostate cancer
  Prostate neoplasm
• UniProt ID: B4GT4_HUMAN
• EC Number: 2.4.1.-; 2.4.1.275; 2.4.1.90
• Pfam ID: PF02709 ; PF13733
• Sequence:
  MGFNLTFHLSYKFRLLLLLTLCLTVVGWATSNYFVGAIQEIPKAKEFMANFHKTLILGKG
  KTLTNEASTKKVELDNCPSVSPYLRGQSKLIFKPDLTLEEVQAENPKVSRGRYRPQECKA
  LQRVAILVPHRNREKHLMYLLEHLHPFLQRQQLDYGIYVIHQAEGKKFNRAKLLNVGYLE
  ALKEENWDCFIFHDVDLVPENDFNLYKCEEHPKHLVVGRNSTGYRLRYSGYFGGVTALSR
  EQFFKVNGFSNNYWGWGGEDDDLRLRVELQRMKISRPLPEVGKYTMVFHTRDKGNEVNAE
  RMKLLHQVSRVWRTDGLSSCSYKLVSVEHNPLYINITVDFWFGA
• Function: Galactose (Gal) transferase involved in the synthesis of terminal N-acetyllactosamine (LacNac) unit present on glycan chains of glycoproteins and glycosphingolipids. Catalyzes the transfer of Gal residue via a beta1->4 linkage from UDP-Gal to the non-reducing terminal N-acetyl glucosamine 6-O-sulfate (6-O-sulfoGlcNAc) in the linearly growing chain of both N- and O-linked keratan sulfate proteoglycans. Cooperates with B3GNT7 N-acetyl glucosamine transferase and CHST6 and CHST1 sulfotransferases to construct and elongate mono- and disulfated disaccharide units [->3Galbeta1->4(6-sulfoGlcNAcbeta)1->] and [->3(6-sulfoGalbeta)1->4(6-sulfoGlcNAcbeta)1->] within keratan sulfate polymer. Transfers Gal residue via a beta1->4 linkage to terminal 6-O-sulfoGlcNAc within the LacNac unit of core 2 O-glycans forming 6-sulfo-sialyl-Lewis X (sLex). May contribute to the generation of sLex epitope on mucin-type glycoproteins that serve as ligands for SELL/L-selectin, a major regulator of leukocyte migration. In the biosynthesis pathway of neolacto-series glycosphingolipids, transfers Gal residue via a beta1->4 linkage to terminal GlcNAc of a lactotriaosylceramide (Lc3Cer) acceptor to form a neolactotetraosylceramide.
• Tissue Specificity: Highest expression is observed in placenta, pancreas, kidney and heart . Expressed in corneal epithelial cells .
• KEGG Pathway:
  Glycosaminoglycan biosynthesis - keratan sulfate (hsa00533)
  Glycosphingolipid biosynthesis - lacto and neolacto series (hsa00601)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  N-Glycan antennae elongation (R-HSA-975577)
  Keratan sulfate biosynthesis (R-HSA-2022854)
• BioCyc Pathway: MetaCyc:HS04504-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
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Beta-1,4-galactosyltransferase 4 (B4GALT4).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Beta-1,4-galactosyltransferase 4 (B4GALT4).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Beta-1,4-galactosyltransferase 4 (B4GALT4).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Beta-1,4-galactosyltransferase 4 (B4GALT4).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Beta-1,4-galactosyltransferase 4 (B4GALT4).	[6]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Beta-1,4-galactosyltransferase 4 (B4GALT4).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Beta-1,4-galactosyltransferase 4 (B4GALT4).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Beta-1,4-galactosyltransferase 4 (B4GALT4).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Beta-1,4-galactosyltransferase 4 (B4GALT4).	[12]

2 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 decreases the methylation of Beta-1,4-galactosyltransferase 4 (B4GALT4).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Beta-1,4-galactosyltransferase 4 (B4GALT4).	[10]

References

• [1] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [2] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.