Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYIQT2F)

• DOT Name: Beta-1,4-galactosyltransferase 2 (B4GALT2)
• Synonyms: Beta-1,4-GalTase 2; Beta4Gal-T2; b4Gal-T2; 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; UDP-Gal:beta-GlcNAc beta-1,4-galactosyltransferase 2; UDP-galactose:beta-N-acetylglucosamine beta-1,4-galactosyltransferase 2
• Gene Name: B4GALT2
• Related Disease:
  Diabetic retinopathy
  Attention deficit hyperactivity disorder
  Colorectal carcinoma
  Uterine cervix neoplasm
• UniProt ID: B4GT2_HUMAN
• EC Number: 2.4.1.-; 2.4.1.22; 2.4.1.38; 2.4.1.90
• Pfam ID: PF02709 ; PF13733
• Sequence:
  MSRLLGGTLERVCKAVLLLCLLHFLVAVILYFDVYAQHLAFFSRFSARGPAHALHPAASS
  SSSSSNCSRPNATASSSGLPEVPSALPGPTAPTLPPCPDSPPGLVGRLLIEFTSPMPLER
  VQRENPGVLMGGRYTPPDCTPAQTVAVIIPFRHREHHLRYWLHYLHPILRRQRLRYGVYV
  INQHGEDTFNRAKLLNVGFLEALKEDAAYDCFIFSDVDLVPMDDRNLYRCGDQPRHFAIA
  MDKFGFRLPYAGYFGGVSGLSKAQFLRINGFPNEYWGWGGEDDDIFNRISLTGMKISRPD
  IRIGRYRMIKHDRDKHNEPNPQRFTKIQNTKLTMKRDGIGSVRYQVLEVSRQPLFTNITV
  DIGRPPSWPPRG
• Function: Responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids. Can produce lactose.
• Tissue Specificity: Weakly expressed in various tissues. Highest expression in prostate, testis, ovary, intestine, muscle, and in fetal 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:
  N-Glycan antennae elongation (R-HSA-975577)
  Keratan sulfate biosynthesis (R-HSA-2022854)
• BioCyc Pathway: MetaCyc:HS04130-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic retinopathy	DISHGUJM	Definitive	Biomarker	[1]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Uterine cervix neoplasm	DIS0BYVV	Strong	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Beta-1,4-galactosyltransferase 2 (B4GALT2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Beta-1,4-galactosyltransferase 2 (B4GALT2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Beta-1,4-galactosyltransferase 2 (B4GALT2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Beta-1,4-galactosyltransferase 2 (B4GALT2).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Beta-1,4-galactosyltransferase 2 (B4GALT2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Beta-1,4-galactosyltransferase 2 (B4GALT2).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Beta-1,4-galactosyltransferase 2 (B4GALT2).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Beta-1,4-galactosyltransferase 2 (B4GALT2).	[11]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Beta-1,4-galactosyltransferase 2 (B4GALT2).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Beta-1,4-galactosyltransferase 2 (B4GALT2).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Beta-1,4-galactosyltransferase 2 (B4GALT2).	[14]

References

• [1] Tumor necrosis factor-alpha in diabetic plasma increases the activity of core 2 GlcNAc-T and adherence of human leukocytes to retinal endothelial cells: significance of core 2 GlcNAc-T in diabetic retinopathy.Diabetes. 2004 Nov;53(11):2968-76. doi: 10.2337/diabetes.53.11.2968.
• [2] Integrated Analysis of microRNA and mRNA Expression Profiles: An Attempt to Disentangle the Complex Interaction Network in Attention Deficit Hyperactivity Disorder.Brain Sci. 2019 Oct 22;9(10):288. doi: 10.3390/brainsci9100288.
• [3] Biochemical and functional characterization of glycosylation-associated mutational landscapes in colon cancer.Sci Rep. 2016 Mar 23;6:23642. doi: 10.1038/srep23642.
• [4] beta4GalT-II increases cisplatin-induced apoptosis in HeLa cells depending on its Golgi localization.Biochem Biophys Res Commun. 2007 Jun 22;358(1):41-6. doi: 10.1016/j.bbrc.2007.04.044. Epub 2007 Apr 18.
• [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] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [12] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [15] 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.