Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNTM2SP)

• DOT Name: Carbohydrate sulfotransferase 15 (CHST15)
• Synonyms: EC 2.8.2.33; B-cell RAG-associated gene protein; hBRAG; N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase; GalNAc4S-6ST
• Gene Name: CHST15
• UniProt ID: CHSTF_HUMAN
• EC Number: 2.8.2.33
• Pfam ID: PF00685
• Sequence:
  MRHCINCCIQLLPDGAHKQQVNCQGGPHHGHQACPTCKGENKILFRVDSKQMNLLAVLEV
  RTEGNENWGGFLRFKKGKRCSLVFGLIIMTLVMASYILSGAHQELLISSPFHYGGFPSNP
  SLMDSENPSDTKEHHHQSSVNNISYMKDYPSIKLIINSITTRIEFTTRQLPDLEDLKKQE
  LHMFSVIPNKFLPNSKSPCWYEEFSGQNTTDPYLTNSYVLYSKRFRSTFDALRKAFWGHL
  AHAHGKHFRLRCLPHFYIIGQPKCGTTDLYDRLRLHPEVKFSAIKEPHWWTRKRFGIVRL
  RDGLRDRYPVEDYLDLFDLAAHQIHQGLQASSAKEQSKMNTIIIGEASASTMWDNNAWTF
  FYDNSTDGEPPFLTQDFIHAFQPNARLIVMLRDPVERLYSDYLYFASSNKSADDFHEKVT
  EALQLFENCMLDYSLRACVYNNTLNNAMPVRLQVGLYAVYLLDWLSVFDKQQFLILRLED
  HASNVKYTMHKVFQFLNLGPLSEKQEALMTKSPASNARRPEDRNLGPMWPITQKILRDFY
  RPFNARLAQVLADEAFAWKTT
• Function: Sulfotransferase that transfers sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the C-6 hydroxyl group of the GalNAc 4-sulfate residue of chondroitin sulfate A and forms chondroitin sulfate E containing GlcA-GalNAc(4,6-SO(4)) repeating units. It also transfers sulfate to a unique non-reducing terminal sequence, GalNAc(4SO4)-GlcA(2SO4)-GalNAc(6SO4), to yield a highly sulfated structure similar to the structure found in thrombomodulin chondroitin sulfate. May also act as a B-cell receptor involved in BCR ligation-mediated early activation that mediate regulatory signals key to B-cell development and/or regulation of B-cell-specific RAG expression; however such results are unclear in vivo.
• Tissue Specificity: Expressed in B-cell-enriched tissues but not in fetal or adult thymus. Expressed in fetal and adult spleen, lymph node, tonsil, bone marrow and peripheral leukocytes. Not expressed in T-cells. In pro-B, pre-B, and mature B-cell lines, it colocalizes with RAG1.
• KEGG Pathway: Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate (hsa00532)
• Reactome Pathway: Chondroitin sulfate biosynthesis (R-HSA-2022870)
• BioCyc Pathway: MetaCyc:HS11694-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

24 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 Carbohydrate sulfotransferase 15 (CHST15).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Carbohydrate sulfotransferase 15 (CHST15).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Carbohydrate sulfotransferase 15 (CHST15).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Carbohydrate sulfotransferase 15 (CHST15).	[7]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[12]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[15]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[19]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[20]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of Carbohydrate sulfotransferase 15 (CHST15).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Carbohydrate sulfotransferase 15 (CHST15).	[17]

References

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• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
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• [11] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [17] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [19] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [20] 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.