Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH0RQYA)

• DOT Name: Sulfotransferase 1B1 (SULT1B1)
• Synonyms: ST1B1; EC 2.8.2.1; Sulfotransferase 1B2; Sulfotransferase family cytosolic 1B member 1; Thyroid hormone sulfotransferase
• Gene Name: SULT1B1
• Related Disease: Schizophrenia
• UniProt ID: ST1B1_HUMAN
• PDB ID: 2Z5F; 3CKL
• EC Number: 2.8.2.1
• Pfam ID: PF00685
• Sequence:
  MLSPKDILRKDLKLVHGYPMTCAFASNWEKIEQFHSRPDDIVIATYPKSGTTWVSEIIDM
  ILNDGDIEKCKRGFITEKVPMLEMTLPGLRTSGIEQLEKNPSPRIVKTHLPTDLLPKSFW
  ENNCKMIYLARNAKDVSVSYYHFDLMNNLQPFPGTWEEYLEKFLTGKVAYGSWFTHVKNW
  WKKKEEHPILFLYYEDMKENPKEEIKKIIRFLEKNLNDEILDRIIHHTSFEVMKDNPLVN
  YTHLPTTVMDHSKSPFMRKGTAGDWKNYFTVAQNEKFDAIYETEMSKTALQFRTEI
• Function: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of dopamine, small phenols such as 1-naphthol and p-nitrophenol and thyroid hormones, including 3,3'-diiodothyronine, triidothyronine (T3) and reverse triiodothyronine (rT3). May play a role in gut microbiota-host metabolic interaction. O-sulfonates 4-ethylphenol (4-EP), a dietary tyrosine-derived metabolite produced by gut bacteria. The product 4-EPS crosses the blood-brain barrier and may negatively regulate oligodendrocyte maturation and myelination, affecting the functional connectivity of different brain regions associated with the limbic system.
• Tissue Specificity: Highly expressed in the liver, peripheral blood leukocytes, colon (mucosal lining), small intestine (jejunum) and spleen. A lesser expression was observed in the lung, placenta and thymus.
• Reactome Pathway: Cytosolic sulfonation of small molecules (R-HSA-156584)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	No Known	Unknown	[1]

This DOT Affected the Biotransformations of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Sulfotransferase 1B1 (SULT1B1) increases the sulfation of Triclosan.	[12]
Lidocaine	DML4ZOT	Approved	Sulfotransferase 1B1 (SULT1B1) increases the sulfation of Lidocaine.	[14]
Benzyl alcohol	DMBVYDI	Approved	Sulfotransferase 1B1 (SULT1B1) increases the sulfation of Benzyl alcohol.	[15]

This DOT Affected the Regulation of Drug Effects of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Diethylstilbestrol	DMN3UXQ	Approved	Sulfotransferase 1B1 (SULT1B1) increases the metabolism of Diethylstilbestrol.	[13]
Ethinyl estradiol	DMODJ40	Approved	Sulfotransferase 1B1 (SULT1B1) increases the metabolism of Ethinyl estradiol.	[13]
N-nonylphenol	DMH3OUX	Investigative	Sulfotransferase 1B1 (SULT1B1) increases the metabolism of N-nonylphenol.	[13]

7 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 1B1 (SULT1B1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sulfotransferase 1B1 (SULT1B1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sulfotransferase 1B1 (SULT1B1).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Sulfotransferase 1B1 (SULT1B1).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Sulfotransferase 1B1 (SULT1B1).	[7]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of Sulfotransferase 1B1 (SULT1B1).	[8]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Sulfotransferase 1B1 (SULT1B1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Sulfotransferase 1B1 (SULT1B1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sulfotransferase 1B1 (SULT1B1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Sulfotransferase 1B1 (SULT1B1).	[10]

References

• [1] De novo mutations in schizophrenia implicate synaptic networks. Nature. 2014 Feb 13;506(7487):179-84. doi: 10.1038/nature12929. Epub 2014 Jan 22.
• [2] 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.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
• [6] Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor. J Steroid Biochem Mol Biol. 2016 Oct;163:77-87.
• [7] Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins. Cell Biol Toxicol. 2012 Apr;28(2):69-87.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Development of in vitro 3D cell model from hepatocellular carcinoma (HepG2) cell line and its application for genotoxicity testing. Arch Toxicol. 2019 Nov;93(11):3321-3333. doi: 10.1007/s00204-019-02576-6. Epub 2019 Sep 21.
• [12] Phase II metabolism of betulin by rat and human UDP-glucuronosyltransferases and sulfotransferases. Chem Biol Interact. 2019 Apr 1;302:190-195. doi: 10.1016/j.cbi.2019.02.009. Epub 2019 Feb 15.
• [13] Sulfation of environmental estrogen-like chemicals by human cytosolic sulfotransferases. Biochem Biophys Res Commun. 2000 Jan 7;267(1):80-4. doi: 10.1006/bbrc.1999.1935.
• [14] Studies on sulfation of synthesized metabolites from the local anesthetics ropivacaine and lidocaine using human cloned sulfotransferases. Drug Metab Dispos. 1999 Sep;27(9):1057-63.
• [15] Sulfation of benzyl alcohol by the human cytosolic sulfotransferases (SULTs): a systematic analysis. J Appl Toxicol. 2016 Sep;36(9):1090-4.