Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT85V4QV)

• DOT Name: Beta-1,4 N-acetylgalactosaminyltransferase 2 (B4GALNT2)
• Synonyms: EC 2.4.1.-; Sd(a) beta-1,4-GalNAc transferase; UDP-GalNAc:Neu5Aca2-3Galb-R b1,4-N-acetylgalactosaminyltransferase
• Gene Name: B4GALNT2
• Related Disease:
  Advanced cancer
  Campomelic dysplasia
  Carcinoma
  Craniometaphyseal dysplasia, autosomal dominant
  Duchenne muscular dystrophy
  Gastric neoplasm
  Influenza
  leukaemia
  Leukemia
  Muscular dystrophy
  Neoplasm
  Cerebrotendinous xanthomatosis
  Coronary heart disease
• UniProt ID: B4GN2_HUMAN
• EC Number: 2.4.1.-
• Pfam ID: PF00535
• Sequence:
  MGSAGFSVGKFHVEVASRGRECVSGTPECGNRLGSAGFGALCLELRGADPAWGPFAAHGR
  SRRQGSRFLWLLKILVIILVLGIVGFMFGSMFLQAVFSSPKPELPSPAPGVQKLKLLPEE
  RLRNLFSYDGIWLFPKNQCKCEANKEQGGYNFQDAYGQSDLPAVKARRQAEFEHFQRREG
  LPRPLPLLVQPNLPFGYPVHGVEVMPLHTVPIPGLQFEGPDAPVYEVTLTASLGTLNTLA
  DVPDSVVQGRGQKQLIISTSDRKLLKFILQHVTYTSTGYQHQKVDIVSLESRSSVAKFPV
  TIRHPVIPKLYDPGPERKLRNLVTIATKTFLRPHKLMIMLRSIREYYPDLTVIVADDSQK
  PLEIKDNHVEYYTMPFGKGWFAGRNLAISQVTTKYVLWVDDDFLFNEETKIEVLVDVLEK
  TELDVVGGSVLGNVFQFKLLLEQSENGACLHKRMGFFQPLDGFPSCVVTSGVVNFFLAHT
  ERLQRVGFDPRLQRVAHSEFFIDGLGTLLVGSCPEVIIGHQSRSPVVDSELAALEKTYNT
  YRSNTLTRVQFKLALHYFKNHLQCAA
• Function: Involved in the synthesis of the Sd(a) antigen (Sia-alpha2,3-[GalNAc-beta1,4]Gal-beta1,4-GlcNAc), a carbohydrate determinant expressed on erythrocytes, the colonic mucosa and other tissues. Transfers a beta-1,4-linked GalNAc to the galactose residue of an alpha-2,3-sialylated chain.
• Tissue Specificity: Widely expressed. Highly expressed in colon and to a lesser extent in kidney, stomach, ileum and rectum.
• KEGG Pathway:
  Glycosphingolipid biosynthesis - lacto and neolacto series (hsa00601)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Lewis blood group biosynthesis (R-HSA-9037629)
  Asparagine N-linked glycosylation (R-HSA-446203)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Campomelic dysplasia	DISVTW53	Strong	Altered Expression	[2]
Carcinoma	DISH9F1N	Strong	Posttranslational Modification	[3]
Craniometaphyseal dysplasia, autosomal dominant	DISU12OO	Strong	Altered Expression	[2]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Altered Expression	[2]
Gastric neoplasm	DISOKN4Y	Strong	Posttranslational Modification	[3]
Influenza	DIS3PNU3	Strong	Altered Expression	[4]
leukaemia	DISS7D1V	Strong	Biomarker	[5]
Leukemia	DISNAKFL	Strong	Biomarker	[5]
Muscular dystrophy	DISJD6P7	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[6]
Cerebrotendinous xanthomatosis	DIST9FNK	moderate	Altered Expression	[7]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[8]

2 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-1,4 N-acetylgalactosaminyltransferase 2 (B4GALNT2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Beta-1,4 N-acetylgalactosaminyltransferase 2 (B4GALNT2).	[10]

References

• [1] B4GALNT2 gene expression controls the biosynthesis of Sda and sialyl Lewis X antigens in healthy and cancer human gastrointestinal tract.Int J Biochem Cell Biol. 2014 Aug;53:442-9. doi: 10.1016/j.biocel.2014.06.009. Epub 2014 Jun 19.
• [2] Congenital muscular dystrophies involving the O-mannose pathway.Curr Mol Med. 2007 Jun;7(4):417-25. doi: 10.2174/156652407780831601.
• [3] DNA hypermethylation contributes to incomplete synthesis of carbohydrate determinants in gastrointestinal cancer.Gastroenterology. 2008 Jul;135(1):142-151.e3. doi: 10.1053/j.gastro.2008.03.031. Epub 2008 Mar 21.
• [4] A CRISPR Activation Screen Identifies a Pan-avian Influenza Virus Inhibitory Host Factor.Cell Rep. 2017 Aug 15;20(7):1503-1512. doi: 10.1016/j.celrep.2017.07.060.
• [5] B4GALT family mediates the multidrug resistance of human leukemia cells by regulating the hedgehog pathway and the expression of p-glycoprotein and multidrug resistance-associated protein 1.Cell Death Dis. 2013 Jun 6;4(6):e654. doi: 10.1038/cddis.2013.186.
• [6] The Immunological Regulation Roles of Porcine -1, 4 Galactosyltransferase V (B4GALT5) in PRRSV Infection.Front Cell Infect Microbiol. 2018 Mar 1;8:48. doi: 10.3389/fcimb.2018.00048. eCollection 2018.
• [7] Sarcospan-dependent Akt activation is required for utrophin expression and muscle regeneration.J Cell Biol. 2012 Jun 25;197(7):1009-27. doi: 10.1083/jcb.201110032.
• [8] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [9] 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.
• [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.