Details of Drug Off-Target (DOT)

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

• DOT Name: Carbohydrate sulfotransferase 12 (CHST12)
• Synonyms: EC 2.8.2.5; Chondroitin 4-O-sulfotransferase 2; Chondroitin 4-sulfotransferase 2; C4ST-2; C4ST2; Sulfotransferase Hlo
• Gene Name: CHST12
• Related Disease:
  Lupus
  Systemic lupus erythematosus
• UniProt ID: CHSTC_HUMAN
• EC Number: 2.8.2.5
• Pfam ID: PF03567
• Sequence:
  MTKARLFRLWLVLGSVFMILLIIVYWDSAGAAHFYLHTSFSRPHTGPPLPTPGPDRDREL
  TADSDVDEFLDKFLSAGVKQSDLPRKETEQPPAPGSMEESVRGYDWSPRDARRSPDQGRQ
  QAERRSVLRGFCANSSLAFPTKERAFDDIPNSELSHLIVDDRHGAIYCYVPKVACTNWKR
  VMIVLSGSLLHRGAPYRDPLRIPREHVHNASAHLTFNKFWRRYGKLSRHLMKVKLKKYTK
  FLFVRDPFVRLISAFRSKFELENEEFYRKFAVPMLRLYANHTSLPASAREAFRAGLKVSF
  ANFIQYLLDPHTEKLAPFNEHWRQVYRLCHPCQIDYDFVGKLETLDEDAAQLLQLLQVDR
  QLRFPPSYRNRTASSWEEDWFAKIPLAWRQQLYKLYEADFVLFGYPKPENLLRD
• Function: Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin and desulfated dermatan sulfate. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. Activity toward partially desulfated dermatan sulfate is however lower. Does not form 4, 6-di-O-sulfated GalNAc when chondroitin sulfate C is used as an acceptor.
• Tissue Specificity: Widely expressed. Expressed a high level in spinal chord, heart, spleen, thyroid, pituitary gland, adrenal gland, peripheral blood leukocytes, thymus, lung, small intestine, fetal kidney, fetal spleen and fetal lung.
• KEGG Pathway: Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate (hsa00532)
• Reactome Pathway: Chondroitin sulfate biosynthesis (R-HSA-2022870)
• BioCyc Pathway: MetaCyc:HS06130-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
Lupus	DISOKJWA	Strong	Biomarker	[1]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Carbohydrate sulfotransferase 12 (CHST12).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Carbohydrate sulfotransferase 12 (CHST12).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Carbohydrate sulfotransferase 12 (CHST12).	[4]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Carbohydrate sulfotransferase 12 (CHST12).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Carbohydrate sulfotransferase 12 (CHST12).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Carbohydrate sulfotransferase 12 (CHST12).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Carbohydrate sulfotransferase 12 (CHST12).	[7]

References

• [1] Renal involvement in lupus is characterized by unique DNA methylation changes in nave CD4+ T cells.J Autoimmun. 2015 Jul;61:29-35. doi: 10.1016/j.jaut.2015.05.003. Epub 2015 May 23.
• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.