Details of Drug Off-Target (DOT)

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

• DOT Name: Protein-tyrosine sulfotransferase 1 (TPST1)
• Synonyms: EC 2.8.2.20; Tyrosylprotein sulfotransferase 1; TPST-1
• Gene Name: TPST1
• Related Disease:
  Colorectal carcinoma
  Shwachman-Diamond syndrome
  Lung cancer
  Lung carcinoma
  Neoplasm
  Gout
• UniProt ID: TPST1_HUMAN
• PDB ID: 5WRI; 5WRJ
• EC Number: 2.8.2.20
• Pfam ID: PF13469
• Sequence:
  MVGKLKQNLLLACLVISSVTVFYLGQHAMECHHRIEERSQPVKLESTRTTVRTGLDLKAN
  KTFAYHKDMPLIFIGGVPRSGTTLMRAMLDAHPDIRCGEETRVIPRILALKQMWSRSSKE
  KIRLDEAGVTDEVLDSAMQAFLLEIIVKHGEPAPYLCNKDPFALKSLTYLSRLFPNAKFL
  LMVRDGRASVHSMISRKVTIAGFDLNSYRDCLTKWNRAIETMYNQCMEVGYKKCMLVHYE
  QLVLHPERWMRTLLKFLQIPWNHSVLHHEEMIGKAGGVSLSKVERSTDQVIKPVNVGALS
  KWVGKIPPDVLQDMAVIAPMLAKLGYDPYANPPNYGKPDPKIIENTRRVYKGEFQLPDFL
  KEKPQTEQVE
• Function: Catalyzes the O-sulfation of tyrosine residues within acidic motifs of polypeptides, using 3'-phosphoadenylyl sulfate (PAPS) as cosubstrate.
• Tissue Specificity: Ubiquitous. Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
• 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)
• BioCyc Pathway: MetaCyc:HS10030-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[1]
Shwachman-Diamond syndrome	DISW57NW	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	moderate	Biomarker	[3]
Lung carcinoma	DISTR26C	moderate	Biomarker	[3]
Neoplasm	DISZKGEW	moderate	Altered Expression	[3]
Gout	DISHC0U7	Limited	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein-tyrosine sulfotransferase 1 (TPST1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein-tyrosine sulfotransferase 1 (TPST1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein-tyrosine sulfotransferase 1 (TPST1).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein-tyrosine sulfotransferase 1 (TPST1).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Protein-tyrosine sulfotransferase 1 (TPST1).	[8]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Protein-tyrosine sulfotransferase 1 (TPST1).	[9]
Tibolone	DM78XFG	Approved	Tibolone increases the expression of Protein-tyrosine sulfotransferase 1 (TPST1).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein-tyrosine sulfotransferase 1 (TPST1).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Protein-tyrosine sulfotransferase 1 (TPST1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein-tyrosine sulfotransferase 1 (TPST1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Protein-tyrosine sulfotransferase 1 (TPST1).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein-tyrosine sulfotransferase 1 (TPST1).	[16]

References

• [1] Genetic variation in microRNA-binding site and prognosis of patients with colorectal cancer.J Cancer Res Clin Oncol. 2015 Jan;141(1):35-41. doi: 10.1007/s00432-014-1780-6. Epub 2014 Jul 31.
• [2] Fine mapping of the locus for Shwachman-Diamond syndrome at 7q11, identification of shared disease haplotypes, and exclusion of TPST1 as a candidate gene.Eur J Hum Genet. 2002 Apr;10(4):250-8. doi: 10.1038/sj.ejhg.5200798.
• [3] Tyrosylprotein sulfotransferase 1 expression is negatively correlated with cMet and lymph node metastasis in human lung cancer.Mol Med Rep. 2015 Oct;12(4):5217-22. doi: 10.3892/mmr.2015.4096. Epub 2015 Jul 20.
• [4] Gout and type 2 diabetes have a mutual inter-dependent effect on genetic risk factors and higher incidences.Rheumatology (Oxford). 2012 Apr;51(4):715-20. doi: 10.1093/rheumatology/ker373. Epub 2011 Dec 16.
• [5] 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.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [9] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [10] A microarray study on the effect of four hormone therapy regimens on gene transcription in whole blood from healthy postmenopausal women. Thromb Res. 2012 Jul;130(1):45-51. doi: 10.1016/j.thromres.2011.12.009. Epub 2012 Jan 2.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [15] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.