Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3C3VWX)

• DOT Name: Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (ST6GALNAC6)
• Synonyms: EC 2.4.99.-; GalNAc alpha-2,6-sialyltransferase VI; ST6GalNAc VI; ST6GalNAcVI; hST6GalNAc VI; Sialyltransferase 7F; SIAT7-F
• Gene Name: ST6GALNAC6
• Related Disease: Kidney cancer
• UniProt ID: SIA7F_HUMAN
• EC Number: 2.4.99.-
• Pfam ID: PF00777
• Sequence:
  MACSRPPSQCEPTSLPPGPPAGRRHLPLSRRRREMSSNKEQRSAVFVILFALITILILYS
  SNSANEVFHYGSLRGRSRRPVNLKKWSITDGYVPILGNKTLPSRCHQCVIVSSSSHLLGT
  KLGPEIERAECTIRMNDAPTTGYSADVGNKTTYRVVAHSSVFRVLRRPQEFVNRTPETVF
  IFWGPPSKMQKPQGSLVRVIQRAGLVFPNMEAYAVSPGRMRQFDDLFRGETGKDREKSHS
  WLSTGWFTMVIAVELCDHVHVYGMVPPNYCSQRPRLQRMPYHYYEPKGPDECVTYIQNEH
  SRKGNHHRFITEKRVFSSWAQLYGITFSHPSWT
• Function: Transfers the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc onto glycoproteins and glycolipids, forming an alpha-2,6-linkage. Produces branched type disialyl structures by transfer of a sialyl group onto the GalNAc or GlcNAc residue inside backbone core chains having a terminal sialic acid with an alpha-2,3-linkage on Gal. ST6GalNAcVI prefers glycolipids to glycoproteins, predominantly catalyzing the biosynthesis of ganglioside GD1alpha from GM1b. Besides GMb1, MSGG and other glycolipids, it shows activity towards sialyl Lc4Cer generating disialyl Lc4Cer, which can lead to the synthesis of disialyl Lewis a (Le(a)), suggested to be a cancer-associated antigen. Also has activity toward GD1a and GT1b, and can generate DSGG (disialylgalactosylgloboside) from MSGG (monosialylgalactosylgloboside).
• Tissue Specificity: Expressed in kidney, in proximal tubule epithelial cells. Expressed in colon cell lines.
• KEGG Pathway:
  Glycosphingolipid biosynthesis - ganglio series (hsa00604)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Lewis blood group biosynthesis (R-HSA-9037629)
  Sialic acid metabolism (R-HSA-4085001)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Kidney cancer	DISBIPKM	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (ST6GALNAC6).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (ST6GALNAC6).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (ST6GALNAC6).	[4]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (ST6GALNAC6).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (ST6GALNAC6).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (ST6GALNAC6).	[8]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (ST6GALNAC6).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (ST6GALNAC6).	[6]

References

• [1] Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: downregulation of ST6GalNAc VI in renal cancers.Biochem J. 2007 Mar 15;402(3):459-70. doi: 10.1042/BJ20061118.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [6] 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.
• [7] 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.
• [8] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [9] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.