Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBCXEK7)

• DOT Name: Beta-1,4-galactosyltransferase 1 (B4GALT1)
• Synonyms: Beta-1,4-GalTase 1; Beta4Gal-T1; b4Gal-T1; EC 2.4.1.-; Beta-N-acetylglucosaminyl-glycolipid beta-1,4-galactosyltransferase; Beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase; EC 2.4.1.38; Lactose synthase A protein; EC 2.4.1.22; N-acetyllactosamine synthase; EC 2.4.1.90; Nal synthase; Neolactotriaosylceramide beta-1,4-galactosyltransferase; EC 2.4.1.275; UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 1; UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 1
• Gene Name: B4GALT1
• Related Disease:
  Rheumatoid arthritis
  Type-1 diabetes
  Advanced cancer
  B4GALT1-congenital disorder of glycosylation
  Bladder cancer
  Congenital disorder of glycosylation
  Hepatitis
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Neoplasm
  Urinary bladder cancer
  Urinary bladder neoplasm
  Breast cancer
  Breast carcinoma
  Hydrocephalus
  Myopathy
  Adenocarcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  IgA nephropathy
• UniProt ID: B4GT1_HUMAN
• PDB ID: 2AE7; 2AEC; 2AES; 2AGD; 2AH9; 2FY7; 2FYA; 2FYB; 3EE5; 4EE3; 4EE4; 4EE5; 4EEA; 4EEG; 4EEM; 4EEO; 4L41; 6FWT; 6FWU
• EC Number: 2.4.1.-; 2.4.1.22; 2.4.1.275; 2.4.1.38; 2.4.1.90
• Pfam ID: PF02709 ; PF13733
• Sequence:
  MRLREPLLSGSAAMPGASLQRACRLLVAVCALHLGVTLVYYLAGRDLSRLPQLVGVSTPL
  QGGSNSAAAIGQSSGELRTGGARPPPPLGASSQPRPGGDSSPVVDSGPGPASNLTSVPVP
  HTTALSLPACPEESPLLVGPMLIEFNMPVDLELVAKQNPNVKMGGRYAPRDCVSPHKVAI
  IIPFRNRQEHLKYWLYYLHPVLQRQQLDYGIYVINQAGDTIFNRAKLLNVGFQEALKDYD
  YTCFVFSDVDLIPMNDHNAYRCFSQPRHISVAMDKFGFSLPYVQYFGGVSALSKQQFLTI
  NGFPNNYWGWGGEDDDIFNRLVFRGMSISRPNAVVGRCRMIRHSRDKKNEPNPQRFDRIA
  HTKETMLSDGLNSLTYQVLDVQRYPLYTQITVDIGTPS
• Function: [Beta-1,4-galactosyltransferase 1]: The Golgi complex form catalyzes the production of lactose in the lactating mammary gland and could also be responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids; [Processed beta-1,4-galactosyltransferase 1]: The cell surface form functions as a recognition molecule during a variety of cell to cell and cell to matrix interactions, as those occurring during development and egg fertilization, by binding to specific oligosaccharide ligands on opposing cells or in the extracellular matrix.
• Tissue Specificity: Ubiquitously expressed, but at very low levels in fetal and adult brain.
• KEGG Pathway:
  Galactose metabolism (hsa00052)
  N-Glycan biosynthesis (hsa00510)
  Various types of N-glycan biosynthesis (hsa00513)
  Other types of O-glycan biosynthesis (hsa00514)
  Mannose type O-glycan biosynthesis (hsa00515)
  Glycosaminoglycan biosynthesis - keratan sulfate (hsa00533)
  Glycosphingolipid biosynthesis - lacto and neolacto series (hsa00601)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Keratan sulfate biosynthesis (R-HSA-2022854)
  Interaction With Cumulus Cells And The Zona Pellucida (R-HSA-2534343)
  Defective B4GALT1 causes B4GALT1-CDG (CDG-2d) (R-HSA-3656244)
  Defective B4GALT1 causes CDG-2d (R-HSA-4793953)
  Lactose synthesis (R-HSA-5653890)
  Neutrophil degranulation (R-HSA-6798695)
  N-Glycan antennae elongation (R-HSA-975577)
  Pre-NOTCH Processing in Golgi (R-HSA-1912420)
• BioCyc Pathway: MetaCyc:HS01519-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[1]
Type-1 diabetes	DIS7HLUB	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
B4GALT1-congenital disorder of glycosylation	DISAFK7V	Strong	Autosomal recessive	[4]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[3]
Congenital disorder of glycosylation	DIS400QP	Strong	Biomarker	[4]
Hepatitis	DISXXX35	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[5]
leukaemia	DISS7D1V	Strong	Biomarker	[6]
Leukemia	DISNAKFL	Strong	Biomarker	[6]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[7]
Lung cancer	DISCM4YA	Strong	Biomarker	[7]
Lung carcinoma	DISTR26C	Strong	Biomarker	[7]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[9]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[9]
Hydrocephalus	DISIZUF7	moderate	Biomarker	[10]
Myopathy	DISOWG27	moderate	Biomarker	[10]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[11]
Colorectal neoplasm	DISR1UCN	Limited	Biomarker	[11]
IgA nephropathy	DISZ8MTK	Limited	Biomarker	[12]

24 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 1 (B4GALT1).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[16]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[18]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[19]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[20]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[21]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[17]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[22]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[23]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[17]
Estriol	DMOEM2I	Approved	Estriol increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[17]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[24]
HMPL-004	DM29XGY	Phase 3	HMPL-004 increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[25]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[25]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[20]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[25]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[28]
2-tert-butylbenzene-1,4-diol	DMNXI1E	Investigative	2-tert-butylbenzene-1,4-diol increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[25]
N-nonylphenol	DMH3OUX	Investigative	N-nonylphenol increases the expression of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Beta-1,4-galactosyltransferase 1 (B4GALT1).	[27]

References

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• [2] Abnormal islet sphingolipid metabolism in type 1 diabetes.Diabetologia. 2018 Jul;61(7):1650-1661. doi: 10.1007/s00125-018-4614-2. Epub 2018 Apr 18.
• [3] B4GALT1 expression predicts prognosis and adjuvant chemotherapy benefits in muscle-invasive bladder cancer patients.BMC Cancer. 2018 May 24;18(1):590. doi: 10.1186/s12885-018-4497-0.
• [4] B4GALT1-congenital disorders of glycosylation presents as a non-neurologic glycosylation disorder with hepatointestinal involvement. J Pediatr. 2011 Dec;159(6):1041-3.e2. doi: 10.1016/j.jpeds.2011.08.007. Epub 2011 Sep 13.
• [5] Identification of beta-1,4-galactosyltransferase I as a target gene of HBx-induced cell cycle progression of hepatoma cell.J Hepatol. 2008 Dec;49(6):1029-37. doi: 10.1016/j.jhep.2008.09.003. Epub 2008 Sep 26.
• [6] B4GALT1 gene knockdown inhibits the hedgehog pathway and reverses multidrug resistance in the human leukemia K562/adriamycin-resistant cell line.IUBMB Life. 2012 Nov;64(11):889-900. doi: 10.1002/iub.1080. Epub 2012 Sep 29.
• [7] B4GALT1 Is a New Candidate to Maintain the Stemness of Lung Cancer Stem Cells.J Clin Med. 2019 Nov 9;8(11):1928. doi: 10.3390/jcm8111928.
• [8] Elevated beta1,4-galactosyltransferase I in highly metastatic human lung cancer cells. Identification of E1AF as important transcription activator.J Biol Chem. 2005 Apr 1;280(13):12503-16. doi: 10.1074/jbc.M413631200. Epub 2004 Dec 16.
• [9] Estrogen induced -1,4-galactosyltransferase 1 expression regulates proliferation of human breast cancer MCF-7 cells.Biochem Biophys Res Commun. 2012 Oct 5;426(4):620-5. doi: 10.1016/j.bbrc.2012.08.140. Epub 2012 Sep 6.
• [10] Deficiency of UDP-galactose:N-acetylglucosamine beta-1,4-galactosyltransferase I causes the congenital disorder of glycosylation type IId. J Clin Invest. 2002 Mar;109(6):725-33. doi: 10.1172/JCI14010.
• [11] Aberrant promoter methylation of beta-1,4 galactosyltransferase 1 as potential cancer-specific biomarker of colorectal tumors.Genes Chromosomes Cancer. 2012 Dec;51(12):1133-43. doi: 10.1002/gcc.21998. Epub 2012 Aug 25.
• [12] Development of immunoglobulin A nephropathy- like disease in beta-1,4-galactosyltransferase-I-deficient mice.Am J Pathol. 2007 Feb;170(2):447-56. doi: 10.2353/ajpath.2007.060559.
• [13] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
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• [16] Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
• [17] Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1. Mol Endocrinol. 2004 Feb;18(2):402-11. doi: 10.1210/me.2003-0202. Epub 2003 Nov 6.
• [18] 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.
• [19] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [20] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Effects of aspirin on metastasis-associated gene expression detected by cDNA microarray. Acta Pharmacol Sin. 2004 Oct;25(10):1327-33.
• [23] Malathion induced cancer-linked gene expression in human lymphocytes. Environ Res. 2020 Mar;182:109131. doi: 10.1016/j.envres.2020.109131. Epub 2020 Jan 10.
• [24] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [25] Mapping the dynamics of Nrf2 antioxidant and NFB inflammatory responses by soft electrophilic chemicals in human liver cells defines the transition from adaptive to adverse responses. Toxicol In Vitro. 2022 Oct;84:105419. doi: 10.1016/j.tiv.2022.105419. Epub 2022 Jun 17.
• [26] 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.
• [27] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [28] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.