Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9HCUST)

• DOT Name: Carbohydrate sulfotransferase 7 (CHST7)
• Synonyms: EC 2.8.2.-; EC 2.8.2.17; Chondroitin 6-sulfotransferase 2; C6ST-2; Galactose/N-acetylglucosamine/N-acetylglucosamine 6-O-sulfotransferase 5; GST-5; N-acetylglucosamine 6-O-sulfotransferase 4; GlcNAc6ST-4; Gn6st-4
• Gene Name: CHST7
• Related Disease:
  Lung cancer
  Lung carcinoma
  Pneumonitis
  Colorectal carcinoma
• UniProt ID: CHST7_HUMAN
• EC Number: 2.8.2.-; 2.8.2.17
• Pfam ID: PF00685
• Sequence:
  MKGRRRRRREYCKFALLLVLYTLVLLLVPSVLDGGRDGDKGAEHCPGLQRSLGVWSLEAA
  AAGEREQGAEARAAEEGGANQSPRFPSNLSGAVGEAVSREKQHIYVHATWRTGSSFLGEL
  FNQHPDVFYLYEPMWHLWQALYPGDAESLQGALRDMLRSLFRCDFSVLRLYAPPGDPAAR
  APDTANLTTAALFRWRTNKVICSPPLCPGAPRARAEVGLVEDTACERSCPPVAIRALEAE
  CRKYPVVVIKDVRLLDLGVLVPLLRDPGLNLKVVQLFRDPRAVHNSRLKSRQGLLRESIQ
  VLRTRQRGDRFHRVLLAHGVGARPGGQSRALPAAPRADFFLTGALEVICEAWLRDLLFAR
  GAPAWLRRRYLRLRYEDLVRQPRAQLRRLLRFSGLRALAALDAFALNMTRGAAYGADRPF
  HLSARDAREAVHAWRERLSREQVRQVEAACAPAMRLLAYPRSGEEGDAEQPREGETPLEM
  DADGAT
• 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. Preferentially acts on mannose-linked GlcNAc. Also able to catalyze the transfer of sulfate to position 6 of the N-acetylgalactosamine (GalNAc) residue of chondroitin. Also acts on core 2 mucin-type oligosaccharide and N-acetyllactosamine oligomer with a lower efficiency. Has weak or no activity toward keratan sulfate and oligosaccharides containing the Galbeta1-4GlcNAc. Catalyzes 6-O-sulfation of beta-benzyl GlcNAc but not alpha- or beta-benzyl GalNAc.
• Tissue Specificity: Widely expressed. Highly expressed in heart, spleen, liver and ovary. Expressed at lower level in brain, placenta, thyroid, spinal cord and peripheral blood leukocytes. Not expressed in adult skin.
• KEGG Pathway: Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate (hsa00532)
• Reactome Pathway: Chondroitin sulfate biosynthesis (R-HSA-2022870)
• BioCyc Pathway: MetaCyc:HS07394-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Pneumonitis	DIS88E0K	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	moderate	Posttranslational Modification	[2]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Carbohydrate sulfotransferase 7 (CHST7) affects the response to substance of Fluorouracil.	[13]

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 Carbohydrate sulfotransferase 7 (CHST7).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Carbohydrate sulfotransferase 7 (CHST7).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Carbohydrate sulfotransferase 7 (CHST7).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Carbohydrate sulfotransferase 7 (CHST7).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Carbohydrate sulfotransferase 7 (CHST7).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Carbohydrate sulfotransferase 7 (CHST7).	[7]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Carbohydrate sulfotransferase 7 (CHST7).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Carbohydrate sulfotransferase 7 (CHST7).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Carbohydrate sulfotransferase 7 (CHST7).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Carbohydrate sulfotransferase 7 (CHST7).	[12]

References

• [1] Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary inflammations.Clin Chem Lab Med. 2018 Jul 26;56(8):1328-1335. doi: 10.1515/cclm-2017-1157.
• [2] CHST7 Gene Methylation and Sex-Specific Effects on Colorectal Cancer Risk.Dig Dis Sci. 2019 Aug;64(8):2158-2166. doi: 10.1007/s10620-019-05530-9. Epub 2019 Feb 28.
• [3] 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.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Human drug metabolism genes in parathion-and estrogen-treated breast cells. Int J Mol Med. 2007 Dec;20(6):875-81.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [8] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.