Details of Drug Off-Target (DOT)

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

• DOT Name: Beta-1,3-galactosyltransferase 4 (B3GALT4)
• Synonyms: Beta-1,3-GalTase 4; Beta3Gal-T4; Beta3GalT4; GalT4; b3Gal-T4; EC 2.4.1.62; Gal-T2; Ganglioside galactosyltransferase; UDP-galactose:beta-N-acetyl-galactosamine-beta-1,3-galactosyltransferase
• Gene Name: B3GALT4
• Related Disease:
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Ehlers-Danlos syndrome
  Late-onset Parkinson disease
  Parkinson disease
• UniProt ID: B3GT4_HUMAN
• EC Number: 2.4.1.62
• Pfam ID: PF01762
• Sequence:
  MQLRLFRRLLLAALLLVIVWTLFGPSGLGEELLSLSLASLLPAPASPGPPLALPRLLIPN
  QEACSGPGAPPFLLILVCTAPENLNQRNAIRASWGGLREARGLRVQTLFLLGEPNAQHPV
  WGSQGSDLASESAAQGDILQAAFQDSYRNLTLKTLSGLNWAEKHCPMARYVLKTDDDVYV
  NVPELVSELVLRGGRWGQWERSTEPQREAEQEGGQVLHSEEVPLLYLGRVHWRVNPSRTP
  GGRHRVSEEQWPHTWGPFPPYASGTGYVLSASAVQLILKVASRAPLLPLEDVFVGVSARR
  GGLAPTQCVKLAGATHYPLDRCCYGKFLLTSHRLDPWKMQEAWKLVGGSDGERTAPFCSW
  FQGVLGILRCRAIAWLQS
• Function: Involved in GM1/GD1B/GA1 ganglioside biosynthesis.
• Tissue Specificity: Highly expressed in heart, skeletal muscle and pancreas and, to a lesser extent, in brain, placenta, kidney, liver and lung.
• KEGG Pathway:
  Glycosphingolipid biosynthesis - ganglio series (hsa00604)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Lewis blood group biosynthesis (R-HSA-9037629)
• BioCyc Pathway: MetaCyc:HS00059-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Ehlers-Danlos syndrome	DISSVBRR	Strong	Genetic Variation	[4]
Late-onset Parkinson disease	DIS9IOUI	Strong	Altered Expression	[5]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[5]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Beta-1,3-galactosyltransferase 4 (B3GALT4) affects the response to substance of Cisplatin.	[15]

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 4 (B3GALT4).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Beta-1,3-galactosyltransferase 4 (B3GALT4).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Beta-1,3-galactosyltransferase 4 (B3GALT4).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Beta-1,3-galactosyltransferase 4 (B3GALT4).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Beta-1,3-galactosyltransferase 4 (B3GALT4).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Beta-1,3-galactosyltransferase 4 (B3GALT4).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Beta-1,3-galactosyltransferase 4 (B3GALT4).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Beta-1,3-galactosyltransferase 4 (B3GALT4).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Beta-1,3-galactosyltransferase 4 (B3GALT4).	[13]
Octanal	DMTN0OK	Investigative	Octanal decreases the expression of Beta-1,3-galactosyltransferase 4 (B3GALT4).	[14]

References

• [1] DNA Hypomethylation in Blood Links B3GALT4 and ZADH2 to Alzheimer's Disease.J Alzheimers Dis. 2018;66(3):927-934. doi: 10.3233/JAD-180592.
• [2] Downregulation of gangliotetraosylceramide and 1,3-galactosyltransferase-4 gene expression by Smads during transforming growth factor -induced epithelial-mesenchymal transition.Mol Med Rep. 2015 Mar;11(3):2241-7. doi: 10.3892/mmr.2014.2912. Epub 2014 Nov 10.
• [3] Clinical correlation of B7-H3 and B3GALT4 with the prognosis of colorectal cancer.World J Gastroenterol. 2018 Aug 21;24(31):3538-3546. doi: 10.3748/wjg.v24.i31.3538.
• [4] Xylose phosphorylation functions as a molecular switch to regulate proteoglycan biosynthesis.Proc Natl Acad Sci U S A. 2014 Nov 4;111(44):15723-8. doi: 10.1073/pnas.1417993111. Epub 2014 Oct 20.
• [5] siRNA-mediated knockdown of B3GALT4 decreases GM1 ganglioside expression and enhances vulnerability for neurodegeneration.Mol Cell Neurosci. 2019 Mar;95:25-30. doi: 10.1016/j.mcn.2019.01.001. Epub 2019 Jan 3.
• [6] 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.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] 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.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [14] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [15] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.