Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT07MMZS)

• DOT Name: Sulfotransferase 1C2 (SULT1C2)
• Synonyms: ST1C2; EC 2.8.2.1; Sulfotransferase 1C1; SULT1C#1; humSULTC2
• Gene Name: SULT1C2
• UniProt ID: ST1C2_HUMAN
• PDB ID: 3BFX
• EC Number: 2.8.2.1
• Pfam ID: PF00685
• Sequence:
  MALTSDLGKQIKLKEVEGTLLQPATVDNWSQIQSFEAKPDDLLICTYPKAGTTWIQEIVD
  MIEQNGDVEKCQRAIIQHRHPFIEWARPPQPSGVEKAKAMPSPRILKTHLSTQLLPPSFW
  ENNCKFLYVARNAKDCMVSYYHFQRMNHMLPDPGTWEEYFETFINGKVVWGSWFDHVKGW
  WEMKDRHQILFLFYEDIKRDPKHEIRKVMQFMGKKVDETVLDKIVQETSFEKMKENPMTN
  RSTVSKSILDQSISSFMRKGTVGDWKNHFTVAQNERFDEIYRRKMEGTSINFCMEL
• Function: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of phenolic compounds. Does not sulfonate steroids, dopamine, acetaminophen, or alpha-naphthol. Catalyzes the sulfonation of the carcinogenic N-Hydroxy-2-acetylaminofluorene leading to highly reactive intermediates capable of forming DNA adducts, potentially resulting in mutagenesis.
• Tissue Specificity: Found in adult stomach, kidney and thyroid gland, and in fetal kidney and liver.
• Reactome Pathway: Cytosolic sulfonation of small molecules (R-HSA-156584)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
3,4-Dihydroxycinnamic Acid	DMVZL26	Phase 4	Sulfotransferase 1C2 (SULT1C2) increases the sulfation of 3,4-Dihydroxycinnamic Acid.	[21]
Catechol	DML0YEK	Investigative	Sulfotransferase 1C2 (SULT1C2) increases the sulfation of Catechol.	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Sulfotransferase 1C2 (SULT1C2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sulfotransferase 1C2 (SULT1C2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sulfotransferase 1C2 (SULT1C2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sulfotransferase 1C2 (SULT1C2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sulfotransferase 1C2 (SULT1C2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sulfotransferase 1C2 (SULT1C2).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sulfotransferase 1C2 (SULT1C2).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Sulfotransferase 1C2 (SULT1C2).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Sulfotransferase 1C2 (SULT1C2).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Sulfotransferase 1C2 (SULT1C2).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Sulfotransferase 1C2 (SULT1C2).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Sulfotransferase 1C2 (SULT1C2).	[10]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Sulfotransferase 1C2 (SULT1C2).	[12]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Sulfotransferase 1C2 (SULT1C2).	[13]
Chenodiol	DMQ8JIK	Approved	Chenodiol increases the expression of Sulfotransferase 1C2 (SULT1C2).	[14]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Sulfotransferase 1C2 (SULT1C2).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sulfotransferase 1C2 (SULT1C2).	[10]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Sulfotransferase 1C2 (SULT1C2).	[16]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Sulfotransferase 1C2 (SULT1C2).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Sulfotransferase 1C2 (SULT1C2).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Sulfotransferase 1C2 (SULT1C2).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sulfotransferase 1C2 (SULT1C2).	[18]

References

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• [8] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [9] Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor. J Steroid Biochem Mol Biol. 2016 Oct;163:77-87.
• [10] 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.
• [11] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [12] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [13] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [14] Chenodeoxycholic acid significantly impacts the expression of miRNAs and genes involved in lipid, bile acid and drug metabolism in human hepatocytes. Life Sci. 2016 Jul 1;156:47-56.
• [15] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [16] Metabolic patterns and biotransformation activities of resveratrol in human glioblastoma cells: relevance with therapeutic efficacies. PLoS One. 2011;6(11):e27484.
• [17] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [18] 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.
• [19] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [20] 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.
• [21] Cigarette smoke toxicants as substrates and inhibitors for human cytosolic SULTs. Toxicol Appl Pharmacol. 2007 May 15;221(1):13-20. doi: 10.1016/j.taap.2007.02.013. Epub 2007 Feb 28.