Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0QMKO3)

• DOT Name: Sulfotransferase 2B1 (SULT2B1)
• Synonyms: EC 2.8.2.2; Alcohol sulfotransferase; Hydroxysteroid sulfotransferase 2; Sulfotransferase family 2B member 1; Sulfotransferase family cytosolic 2B member 1; ST2B1
• Gene Name: SULT2B1
• Related Disease:
  Ichthyosis, congenital, autosomal recessive 14
  Lamellar ichthyosis
• UniProt ID: ST2B1_HUMAN
• PDB ID: 1Q1Q; 1Q1Z; 1Q20; 1Q22
• EC Number: 2.8.2.2
• Pfam ID: PF00685
• Sequence:
  MDGPAEPQIPGLWDTYEDDISEISQKLPGEYFRYKGVPFPVGLYSLESISLAENTQDVRD
  DDIFIITYPKSGTTWMIEIICLILKEGDPSWIRSVPIWERAPWCETIVGAFSLPDQYSPR
  LMSSHLPIQIFTKAFFSSKAKVIYMGRNPRDVVVSLYHYSKIAGQLKDPGTPDQFLRDFL
  KGEVQFGSWFDHIKGWLRMKGKDNFLFITYEELQQDLQGSVERICGFLGRPLGKEALGSV
  VAHSTFSAMKANTMSNYTLLPPSLLDHRRGAFLRKGVCGDWKNHFTVAQSEAFDRAYRKQ
  MRGMPTFPWDEDPEEDGSPDPEPSPEPEPKPSLEPNTSLEREPRPNSSPSPSPGQASETP
  HPRPS
• Function: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation. Responsible for the sulfation of cholesterol. Catalyzes sulfation of the 3beta-hydroxyl groups of steroids, such as, pregnenolone and dehydroepiandrosterone (DHEA). Preferentially sulfonates cholesterol, while it has also significant activity with pregnenolone and DHEA. Plays a role in epidermal cholesterol metabolism and in the regulation of epidermal proliferation and differentiation ; [Isoform 2]: Sulfonates pregnenolone but not cholesterol.
• Tissue Specificity: Expressed in the stratum granulosum-stratum corneum junction in the skin (at protein level) . Expressed highly in placenta, prostate and trachea and lower expression in the small intestine and lung .
• KEGG Pathway:
  Steroid hormone biosynthesis (hsa00140)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Cytosolic sulfonation of small molecules (R-HSA-156584)
• BioCyc Pathway: MetaCyc:HS01587-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
Ichthyosis, congenital, autosomal recessive 14	DISNNFS1	Strong	Autosomal recessive	[1]
Lamellar ichthyosis	DIS714UN	Supportive	Autosomal recessive	[2]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Prasterone	DM67VKL	Approved	Sulfotransferase 2B1 (SULT2B1) increases the sulfation of Prasterone.	[18]

4 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 Sulfotransferase 2B1 (SULT2B1).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Sulfotransferase 2B1 (SULT2B1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Sulfotransferase 2B1 (SULT2B1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Sulfotransferase 2B1 (SULT2B1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sulfotransferase 2B1 (SULT2B1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Sulfotransferase 2B1 (SULT2B1).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Sulfotransferase 2B1 (SULT2B1).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Sulfotransferase 2B1 (SULT2B1).	[8]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Sulfotransferase 2B1 (SULT2B1).	[9]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Sulfotransferase 2B1 (SULT2B1).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Sulfotransferase 2B1 (SULT2B1).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Sulfotransferase 2B1 (SULT2B1).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Sulfotransferase 2B1 (SULT2B1).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Sulfotransferase 2B1 (SULT2B1).	[16]
Forskolin	DM6ITNG	Investigative	Forskolin decreases the expression of Sulfotransferase 2B1 (SULT2B1).	[17]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] Mutations in SULT2B1 Cause Autosomal-Recessive Congenital Ichthyosis in Humans. Am J Hum Genet. 2017 Jun 1;100(6):926-939. doi: 10.1016/j.ajhg.2017.05.007.
• [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] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [8] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [9] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [10] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [17] Endocrine disruption potentials of organophosphate flame retardants and related mechanisms in H295R and MVLN cell lines and in zebrafish. Aquat Toxicol. 2012 Jun 15;114-115:173-81.
• [18] Human hydroxysteroid sulfotransferase SULT2B1: two enzymes encoded by a single chromosome 19 gene. Genomics. 1998 Nov 1;53(3):284-95. doi: 10.1006/geno.1998.5518.