Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHOU8I2)

• DOT Name: Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1)
• Synonyms: 2-O-sulfotransferase; 2OST; EC 2.8.2.-
• Gene Name: HS2ST1
• Related Disease:
  Mast cell neoplasm
  Melanoma
  Neurofacioskeletal syndrome with or without renal agenesis
• UniProt ID: HS2ST_HUMAN
• EC Number: 2.8.2.-
• Pfam ID: PF03567
• Sequence:
  MGLLRIMMPPKLQLLAVVAFAVAMLFLENQIQKLEESRSKLERAIARHEVREIEQRHTMD
  GPRQDATLDEEEDMVIIYNRVPKTASTSFTNIAYDLCAKNKYHVLHINTTKNNPVMSLQD
  QVRFVKNITSWKEMKPGFYHGHVSYLDFAKFGVKKKPIYINVIRDPIERLVSYYYFLRFG
  DDYRPGLRRRKQGDKKTFDECVAEGGSDCAPEKLWLQIPFFCGHSSECWNVGSRWAMDQA
  KYNLINEYFLVGVTEELEDFIMLLEAALPRFFRGATELYRTGKKSHLRKTTEKKLPTKQT
  IAKLQQSDIWKMENEFYEFALEQFQFIRAHAVREKDGDLYILAQNFFYEKIYPKSN
• Function: Catalyzes the transfer of sulfate to the C2-position of selected hexuronic acid residues within the maturing heparan sulfate (HS). 2-O-sulfation within HS, particularly of iduronate residues, is essential for HS to participate in a variety of high-affinity ligand-binding interactions and signaling processes. Mediates 2-O-sulfation of both L-iduronyl and D-glucuronyl residues.
• KEGG Pathway: Glycosaminoglycan biosynthesis - heparan sulfate / heparin (hsa00534)
• Reactome Pathway: HS-GAG biosynthesis (R-HSA-2022928)
• BioCyc Pathway: MetaCyc:ENSG00000153936-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mast cell neoplasm	DIS6NFMB	Definitive	Biomarker	[1]
Melanoma	DIS1RRCY	Limited	Biomarker	[2]
Neurofacioskeletal syndrome with or without renal agenesis	DIS8KFBJ	Limited	Unknown	[3]

14 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 Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[11]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[12]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[12]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid decreases the expression of Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1).	[16]

References

• [1] Substrate specificity of the heparan sulfate hexuronic acid 2-O-sulfotransferase.Biochemistry. 2001 May 8;40(18):5548-55. doi: 10.1021/bi002926p.
• [2] Melanoma Cell Adhesion and Migration Is Modulated by the Uronyl 2-O Sulfotransferase.PLoS One. 2017 Jan 20;12(1):e0170054. doi: 10.1371/journal.pone.0170054. eCollection 2017.
• [3] Investigating the genetic basis of fever-associated syndromic epilepsies using copy number variation analysis. Epilepsia. 2015 Mar;56(3):e26-32. doi: 10.1111/epi.12920. Epub 2015 Feb 17.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 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.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [14] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [15] 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.
• [16] Arachidonic acid-induced gene expression in colon cancer cells. Carcinogenesis. 2006 Oct;27(10):1950-60.