Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO59SZQ)

• DOT Name: Carbohydrate sulfotransferase 13 (CHST13)
• Synonyms: EC 2.8.2.5; Chondroitin 4-O-sulfotransferase 3; Chondroitin 4-sulfotransferase 3; C4ST-3; C4ST3
• Gene Name: CHST13
• Related Disease:
  Pulmonary arterial hypertension
  Osteoarthritis
• UniProt ID: CHSTD_HUMAN
• EC Number: 2.8.2.5
• Pfam ID: PF03567
• Sequence:
  MGRRCCRRRVLAAACLGAALLLLCAAPRSLRPAFGNRALGSSWLGGEKRSPLQKLYDLDQ
  DPRSTLAKVHRQRRDLLNSACSRHSRRQRLLQPEDLRHVLVDDAHGLLYCYVPKVACTNW
  KRVLLALSGQARGDPRAISAQEAHAPGRLPSLADFSPAEINRRLRAYLAFLFVREPFERL
  ASAYRNKLARPYSAAFQRRYGARIVQRLRPRALPDARARGHDVRFAEFLAYLLDPRTRRE
  EPFNEHWERAHALCHPCRLRYDVVGKFETLAEDAAFVLGLAGASDLSFPGPPRPRGAAAS
  RDLAARLFRDISPFYQRRLFDLYKMDFLLFNYSAPSYLRLL
• Function: Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. Transfers sulfate to the C4 hydroxyl of beta1,4-linked GalNAc that is substituted with a beta-linked glucuronic acid at the C-3 hydroxyl. No activity toward dermatan.
• Tissue Specificity: Highly expressed in adult liver. Expressed at lower level in kidney, lymph nodes and fetal kidney.
• KEGG Pathway: Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate (hsa00532)
• Reactome Pathway: Chondroitin sulfate biosynthesis (R-HSA-2022870)
• BioCyc Pathway: MetaCyc:HS11524-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Pulmonary arterial hypertension	DISP8ZX5	Strong	Genetic Variation	[1]
Osteoarthritis	DIS05URM	moderate	Altered Expression	[2]

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 13 (CHST13).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Carbohydrate sulfotransferase 13 (CHST13).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Carbohydrate sulfotransferase 13 (CHST13).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Carbohydrate sulfotransferase 13 (CHST13).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Carbohydrate sulfotransferase 13 (CHST13).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Carbohydrate sulfotransferase 13 (CHST13).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Carbohydrate sulfotransferase 13 (CHST13).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Carbohydrate sulfotransferase 13 (CHST13).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Carbohydrate sulfotransferase 13 (CHST13).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Carbohydrate sulfotransferase 13 (CHST13).	[12]

References

• [1] CHST3 and CHST13 polymorphisms as predictors of bosentan-induced liver toxicity in Japanese patients with pulmonary arterial hypertension.Pharmacol Res. 2018 Sep;135:259-264. doi: 10.1016/j.phrs.2018.08.011. Epub 2018 Aug 15.
• [2] Altered expression of chondroitin sulfate structure modifying sulfotransferases in the articular cartilage from adult osteoarthritis and Kashin-Beck disease.Osteoarthritis Cartilage. 2017 Aug;25(8):1372-1375. doi: 10.1016/j.joca.2017.02.803. Epub 2017 Mar 6.
• [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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [10] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.