Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU4DD4G)

• DOT Name: Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5)
• Synonyms: EC 2.4.1.155; Alpha-mannoside beta-1,6-N-acetylglucosaminyltransferase V; GlcNAc-T V; GNT-V; Mannoside acetylglucosaminyltransferase 5; N-acetylglucosaminyl-transferase V
• Gene Name: MGAT5
• Related Disease:
  Gastric neoplasm
  Marginal zone lymphoma
  Small lymphocytic lymphoma
  Systemic lupus erythematosus
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Carcinoma
  Colonic neoplasm
  Ductal carcinoma
  Enterovirus infection
  Gastric adenocarcinoma
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Hyperinsulinemia
  Lung neoplasm
  Metastatic malignant neoplasm
  Multiple sclerosis
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Psoriasis
  Stomach cancer
  Ulcerative colitis
  Urinary bladder neoplasm
  Vascular purpura
  Adult glioblastoma
  Glioblastoma multiforme
  Melanoma
  Neuroblastoma
  Clear cell renal carcinoma
  Rheumatoid arthritis
  Type-1 diabetes
• UniProt ID: MGT5A_HUMAN
• PDB ID: 5ZIB; 5ZIC; 6YJQ; 6YJR; 6YJS; 6YJT; 6YJU; 6YJV; 7YYI; 7Z07; 7Z08; 7Z0B
• EC Number: 2.4.1.155
• Pfam ID: PF15027 ; PF15024
• Sequence:
  MALFTPWKLSSQKLGFFLVTFGFIWGMMLLHFTIQQRTQPESSSMLREQILDLSKRYIKA
  LAEENRNVVDGPYAGVMTAYDLKKTLAVLLDNILQRIGKLESKVDNLVVNGTGTNSTNST
  TAVPSLVALEKINVADIINGAQEKCVLPPMDGYPHCEGKIKWMKDMWRSDPCYADYGVDG
  STCSFFIYLSEVENWCPHLPWRAKNPYEEADHNSLAEIRTDFNILYSMMKKHEEFRWMRL
  RIRRMADAWIQAIKSLAEKQNLEKRKRKKVLVHLGLLTKESGFKIAETAFSGGPLGELVQ
  WSDLITSLYLLGHDIRISASLAELKEIMKKVVGNRSGCPTVGDRIVELIYIDIVGLAQFK
  KTLGPSWVHYQCMLRVLDSFGTEPEFNHANYAQSKGHKTPWGKWNLNPQQFYTMFPHTPD
  NSFLGFVVEQHLNSSDIHHINEIKRQNQSLVYGKVDSFWKNKKIYLDIIHTYMEVHATVY
  GSSTKNIPSYVKNHGILSGRDLQFLLRETKLFVGLGFPYEGPAPLEAIANGCAFLNPKFN
  PPKSSKNTDFFIGKPTLRELTSQHPYAEVFIGRPHVWTVDLNNQEEVEDAVKAILNQKIE
  PYMPYEFTCEGMLQRINAFIEKQDFCHGQVMWPPLSALQVKLAEPGQSCKQVCQESQLIC
  EPSFFQHLNKDKDMLKYKVTCQSSELAKDILVPSFDPKNKHCVFQGDLLLFSCAGAHPRH
  QRVCPCRDFIKGQVALCKDCL
• Function: Catalyzes the addition of N-acetylglucosamine (GlcNAc) in beta 1-6 linkage to the alpha-linked mannose of biantennary N-linked oligosaccharides. Catalyzes an important step in the biosynthesis of branched, complex-type N-glycans, such as those found on EGFR, TGFR (TGF-beta receptor) and CDH2. Via its role in the biosynthesis of complex N-glycans, plays an important role in the activation of cellular signaling pathways, reorganization of the actin cytoskeleton, cell-cell adhesion and cell migration. MGAT5-dependent EGFR N-glycosylation enhances the interaction between EGFR and LGALS3 and thereby prevents rapid EGFR endocytosis and prolongs EGFR signaling. Required for efficient interaction between TGFB1 and its receptor. Enhances activation of intracellular signaling pathways by several types of growth factors, including FGF2, PDGF, IGF, TGFB1 and EGF. MGAT5-dependent CDH2 N-glycosylation inhibits CDH2-mediated homotypic cell-cell adhesion and contributes to the regulation of downstream signaling pathways. Promotes cell migration. Contributes to the regulation of the inflammatory response. MGAT5-dependent TCR N-glycosylation enhances the interaction between TCR and LGALS3, limits agonist-induced TCR clustering, and thereby dampens TCR-mediated responses to antigens. Required for normal leukocyte evasation and accumulation at sites of inflammation. Inhibits attachment of monocytes to the vascular endothelium and subsequent monocyte diapedesis ; [Secreted alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A]: Promotes proliferation of umbilical vein endothelial cells and angiogenesis, at least in part by promoting the release of the growth factor FGF2 from the extracellular matrix.
• KEGG Pathway:
  N-Glycan biosynthesis (hsa00510)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  N-Glycan antennae elongation (R-HSA-975577)
  Maturation of spike protein (R-HSA-9694548)
• BioCyc Pathway: MetaCyc:HS07793-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric neoplasm	DISOKN4Y	Definitive	Altered Expression	[1]
Marginal zone lymphoma	DISLZ4AO	Definitive	Genetic Variation	[2]
Small lymphocytic lymphoma	DIS30POX	Definitive	Genetic Variation	[2]
Systemic lupus erythematosus	DISI1SZ7	Definitive	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	Strong	Altered Expression	[5]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[6]
Ductal carcinoma	DIS15EA5	Strong	Biomarker	[7]
Enterovirus infection	DISH2UDP	Strong	Biomarker	[8]
Gastric adenocarcinoma	DISWWLTC	Strong	Altered Expression	[9]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Glioma	DIS5RPEH	Strong	Altered Expression	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[11]
Hyperinsulinemia	DISIDWT6	Strong	Biomarker	[12]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[13]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[14]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[15]
Neoplasm	DISZKGEW	Strong	Altered Expression	[16]
Prostate cancer	DISF190Y	Strong	Biomarker	[17]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[17]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[17]
Psoriasis	DIS59VMN	Strong	Biomarker	[18]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[19]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[20]
Vascular purpura	DIS6ZZMF	Strong	Biomarker	[21]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[22]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[22]
Melanoma	DIS1RRCY	moderate	Altered Expression	[23]
Neuroblastoma	DISVZBI4	moderate	Biomarker	[24]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[3]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[25]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[26]

14 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 A (MGAT5).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5).	[30]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5).	[31]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5).	[32]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5).	[33]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5).	[34]
Propofol	DMB4OLE	Approved	Propofol increases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5).	[35]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5).	[36]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5).	[37]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5).	[38]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (MGAT5).	[39]

References

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• [20] N-acetylglucosaminyltransferase V and beta1-6 branching N-linked oligosaccharides are associated with good prognosis of patients with bladder cancer.Clin Cancer Res. 2006 Apr 15;12(8):2506-11. doi: 10.1158/1078-0432.CCR-05-1938.
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