Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5HP73K)

• DOT Name: Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B (MGAT5B)
• Synonyms: EC 2.4.1.-; EC 2.4.1.155; Alpha-mannoside beta-1,6-N-acetylglucosaminyltransferase B; GlcNAc-T Vb; GNT-Vb; hGnTVb; Mannoside acetylglucosaminyltransferase 5B; N-acetylglucosaminyl-transferase Vb; N-acetylglucosaminyltransferase IX; GNT-IX
• Gene Name: MGAT5B
• Related Disease:
  Advanced cancer
  Ductal carcinoma
  Hepatocellular carcinoma
  Polycystic ovarian syndrome
  Neuroblastoma
  Brain cancer
  Brain neoplasm
  Clear cell renal carcinoma
• UniProt ID: MGT5B_HUMAN
• EC Number: 2.4.1.-; 2.4.1.155
• Pfam ID: PF15024
• Sequence:
  MITVNPDGKIMVRRCLVTLRPFRLFVLGIGFFTLCFLMTSLGGQFSARRLGDSPFTIRTE
  VMGGPESRGVLRKMSDLLELMVKRMDALARLENSSELHRAGGDLHFPADRMPPGAGLMER
  IQAIAQNVSDIAVKVDQILRHSLLLHSKVSEGRRDQCEAPSDPKFPDCSGKVEWMRARWT
  SDPCYAFFGVDGTECSFLIYLSEVEWFCPPLPWRNQTAAQRAPKPLPKVQAVFRSNLSHL
  LDLMGSGKESLIFMKKRTKRLTAQWALAAQRLAQKLGATQRDQKQILVHIGFLTEESGDV
  FSPRVLKGGPLGEMVQWADILTALYVLGHGLRVTVSLKELQSNLGVPPGRGSCPLTMPLP
  FDLIYTDYHGLQQMKRHMGLSFKKYRCRIRVIDTFGTEPAYNHEEYATLHGYRTNWGYWN
  LNPKQFMTMFPHTPDNSFMGFVSEELNETEKRLIKGGKASNMAVVYGKEASIWKLQGKEK
  FLGILNKYMEIHGTVYYESQRPPEVPAFVKNHGLLPQPEFQQLLRKAKLFIGFGFPYEGP
  APLEAIANGCIFLQSRFSPPHSSLNHEFFRGKPTSREVFSQHPYAENFIGKPHVWTVDYN
  NSEEFEAAIKAIMRTQVDPYLPYEYTCEGMLERIHAYIQHQDFCRAPDPALPEAHAPQSP
  FVLAPNATHLEWARNTSLAPGAWPPAHALRAWLAVPGRACTDTCLDHGLICEPSFFPFLN
  SQDAFLKLQVPCDSTESEMNHLYPAFAQPGQECYLQKEPLLFSCAGSNTKYRRLCPCRDF
  RKGQVALCQGCL
• Function: Glycosyltransferase that acts on alpha-linked mannose of N-glycans and O-mannosyl glycans. Catalyzes the transfer of N-acetylglucosamine (GlcNAc) to the beta 1-6 linkage of the mannose residue of GlcNAc-beta1,2-Man-alpha on both the alpha1,3- and alpha1,6-linked mannose arms in the core structure of N-glycan. Also acts on the GlcNAc-beta1,2-Man-alpha1-Ser/Thr moiety, forming a 2,6-branched structure in brain O-mannosyl glycan. Plays an active role in modulating integrin and laminin-dependent adhesion and migration of neuronal cells via its activity in the O-mannosyl glycan pathway.
• Tissue Specificity: Predominantly expressed in brain. Expressed in all areas of the adult and fetal brain. Also expressed at much lower levels in testis, spleen and thymus.
• KEGG Pathway:
  N-Glycan biosynthesis (hsa00510)
  Mannose type O-glycan biosynthesis (hsa00515)
  Metabolic pathways (hsa01100)
• BioCyc Pathway: MetaCyc:HS15606-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Ductal carcinoma	DIS15EA5	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[4]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[5]
Brain cancer	DISBKFB7	Limited	Biomarker	[6]
Brain neoplasm	DISY3EKS	Limited	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[1]

2 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 Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B (MGAT5B).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B (MGAT5B).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B (MGAT5B).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase B (MGAT5B).	[9]

References

• [1] 1,6-N-acetylglucosaminyltransferase V predicts recurrence and survival of patients with clear-cell renal cell carcinoma after surgical resection.World J Urol. 2015 Nov;33(11):1791-9. doi: 10.1007/s00345-014-1451-x. Epub 2015 Jan 29.
• [2] Lectin histochemistry reveals SNA as a prognostic carbohydrate-dependent probe for invasive ductal carcinoma of the breast: a clinicopathological and immunohistochemical auxiliary tool.Int J Clin Exp Pathol. 2014 Apr 15;7(5):2337-49. eCollection 2014.
• [3] The transcriptional profiling of glycogenes associated with hepatocellular carcinoma metastasis.PLoS One. 2014 Sep 18;9(9):e107941. doi: 10.1371/journal.pone.0107941. eCollection 2014.
• [4] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [5] High expression of N-acetylglucosaminyltransferase V in favorable neuroblastomas: Involvement of its effect on apoptosis.FEBS Lett. 2006 Jan 23;580(2):627-32. doi: 10.1016/j.febslet.2005.12.089. Epub 2006 Jan 5.
• [6] Glyco-genes change expression in cancer through aberrant methylation.Biochim Biophys Acta. 2016 Aug;1860(8):1776-85. doi: 10.1016/j.bbagen.2016.01.002. Epub 2016 Jan 12.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [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] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.