Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2XKFCE)

• DOT Name: Protein-tyrosine sulfotransferase 2 (TPST2)
• Synonyms: EC 2.8.2.20; Tyrosylprotein sulfotransferase 2; TPST-2
• Gene Name: TPST2
• Related Disease: Chronic pancreatitis
• UniProt ID: TPST2_HUMAN
• PDB ID: 3AP1; 3AP2; 3AP3
• EC Number: 2.8.2.20
• Pfam ID: PF13469
• Sequence:
  MRLSVRRVLLAAGCALVLVLAVQLGQQVLECRAVLAGLRSPRGAMRPEQEELVMVGTNHV
  EYRYGKAMPLIFVGGVPRSGTTLMRAMLDAHPEVRCGEETRIIPRVLAMRQAWSKSGREK
  LRLDEAGVTDEVLDAAMQAFILEVIAKHGEPARVLCNKDPFTLKSSVYLSRLFPNSKFLL
  MVRDGRASVHSMITRKVTIAGFDLSSYRDCLTKWNKAIEVMYAQCMEVGKEKCLPVYYEQ
  LVLHPRRSLKLILDFLGIAWSDAVLHHEDLIGKPGGVSLSKIERSTDQVIKPVNLEALSK
  WTGHIPGDVVRDMAQIAPMLAQLGYDPYANPPNYGNPDPFVINNTQRVLKGDYKTPANLK
  GYFQVNQNSTSSHLGSS
• Function: Catalyzes the O-sulfation of tyrosine residues within acidic motifs of polypeptides, using 3'-phosphoadenylyl sulfate (PAPS) as cosubstrate.
• Tissue Specificity: Widely expressed.
• Reactome Pathway:
  Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation (R-HSA-163841)
  Defective F8 sulfation at Y1699 (R-HSA-9674519)
  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
Chronic pancreatitis	DISBUOMJ	Limited	Genetic Variation	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Protein-tyrosine sulfotransferase 2 (TPST2) affects the response to substance of Fluorouracil.	[12]

10 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 Protein-tyrosine sulfotransferase 2 (TPST2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein-tyrosine sulfotransferase 2 (TPST2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein-tyrosine sulfotransferase 2 (TPST2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein-tyrosine sulfotransferase 2 (TPST2).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein-tyrosine sulfotransferase 2 (TPST2).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Protein-tyrosine sulfotransferase 2 (TPST2).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Protein-tyrosine sulfotransferase 2 (TPST2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein-tyrosine sulfotransferase 2 (TPST2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein-tyrosine sulfotransferase 2 (TPST2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein-tyrosine sulfotransferase 2 (TPST2).	[11]

References

• [1] Sequence analysis of the human tyrosylprotein sulfotransferase-2 gene in subjects with chronic pancreatitis.Pancreatology. 2010;10(2-3):165-72. doi: 10.1159/000231979. Epub 2010 May 12.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] 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.
• [12] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.