Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9P35BV)

• DOT Name: Carbohydrate sulfotransferase 5 (CHST5)
• Synonyms: EC 2.8.2.-; Galactose/N-acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 4-alpha; GST4-alpha; Intestinal N-acetylglucosamine-6-O-sulfotransferase; I-GlcNAc6ST; Intestinal GlcNAc-6-sulfotransferase; hIGn6ST; N-acetylglucosamine 6-O-sulfotransferase 3; GlcNAc6ST-3; Gn6st-3
• Gene Name: CHST5
• UniProt ID: CHST5_HUMAN
• EC Number: 2.8.2.-
• Pfam ID: PF00685
• Sequence:
  MGMRARVPKVAHSTRRPPAARMWLPRFSSKTVTVLLLAQTTCLLLFIISRPGPSSPAGGE
  DRVHVLVLSSWRSGSSFLGQLFSQHPDVFYLMEPAWHVWTTLSQGSAATLHMAVRDLMRS
  IFLCDMDVFDAYMPQSRNLSAFFNWATSRALCSPPACSAFPRGTISKQDVCKTLCTRQPF
  SLAREACRSYSHVVLKEVRFFNLQVLYPLLSDPALNLRIVHLVRDPRAVLRSREAAGPIL
  ARDNGIVLGTNGKWVEADPHLRLIREVCRSHVRIAEAATLKPPPFLRGRYRLVRFEDLAR
  EPLAEIRALYAFTGLTLTPQLEAWIHNITHGSGIGKPIEAFHTSSRNARNVSQAWRHALP
  FTKILRVQEVCAGALQLLGYRPVYSADQQRDLTLDLVLPRGPDHFSWASPD
• Function: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues and O-linked sugars of mucin-type acceptors. Acts on the non-reducing terminal GlcNAc of short carbohydrate substrates. However, it does not transfer sulfate to longer carbohydrate substrates that have poly-N-acetyllactosamine structures. Has no activity toward keratan. Not involved in generating HEV-expressed ligands for SELL. Its substrate specificity may be influenced by its subcellular location.
• Tissue Specificity: Predominantly expressed in small and large intestines and colon. Weakly expressed in lymphocytes. Not expressed in other tissues. Down-regulated in colonic adenocarcinomas.
• Reactome Pathway: Keratan sulfate biosynthesis (R-HSA-2022854)

Molecular Interaction Atlas (MIA) of This DOT

1 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 Carbohydrate sulfotransferase 5 (CHST5).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Carbohydrate sulfotransferase 5 (CHST5).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Carbohydrate sulfotransferase 5 (CHST5).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Carbohydrate sulfotransferase 5 (CHST5).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Carbohydrate sulfotransferase 5 (CHST5).	[5]

References

• [1] 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.
• [2] Human drug metabolism genes in parathion-and estrogen-treated breast cells. Int J Mol Med. 2007 Dec;20(6):875-81.
• [3] Quantitative proteomic analysis of HepG2 cells treated with quercetin suggests IQGAP1 involved in quercetin-induced regulation of cell proliferation and migration. OMICS. 2009 Apr;13(2):93-103. doi: 10.1089/omi.2008.0075.
• [4] Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
• [5] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.