Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK53GUD)

• DOT Name: Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1)
• Synonyms: EC 2.8.2.30; Heparan sulfate D-glucosaminyl 3-O-sulfotransferase 3B1; 3-OST-3B; Heparan sulfate 3-O-sulfotransferase 3B1; h3-OST-3B
• Gene Name: HS3ST3B1
• Related Disease:
  Acute myelogenous leukaemia
  Breast cancer
  Breast carcinoma
  Hepatitis B virus infection
  Non-small-cell lung cancer
  Pancreatic cancer
  Bladder cancer
  Endometriosis
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: HS3SB_HUMAN
• EC Number: 2.8.2.30
• Pfam ID: PF00685
• Sequence:
  MGQRLSGGRSCLDVPGRLLPQPPPPPPPVRRKLALLFAMLCVWLYMFLYSCAGSCAAAPG
  LLLLGSGSRAAHDPPALATAPDGTPPRLPFRAPPATPLASGKEMAEGAASPEEQSPEVPD
  SPSPISSFFSGSGSKQLPQAIIIGVKKGGTRALLEFLRVHPDVRAVGAEPHFFDRSYDKG
  LAWYRDLMPRTLDGQITMEKTPSYFVTREAPARISAMSKDTKLIVVVRDPVTRAISDYTQ
  TLSKRPDIPTFESLTFKNRTAGLIDTSWSAIQIGIYAKHLEHWLRHFPIRQMLFVSGERL
  ISDPAGELGRVQDFLGLKRIITDKHFYFNKTKGFPCLKKAEGSSRPHCLGKTKGRTHPEI
  DREVVRRLREFYRPFNLKFYQMTGHDFGWD
• Function: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to an N-unsubstituted glucosamine linked to a 2-O-sulfo iduronic acid unit on heparan sulfate. Catalyzes the O-sulfation of glucosamine in IdoUA2S-GlcNS and also in IdoUA2S-GlcNH2. The substrate-specific O-sulfation generates an enzyme-modified heparan sulfate which acts as a binding receptor to Herpes simplex virus-1 (HSV-1) and permits its entry. Unlike HS3ST1/3-OST-1, does not convert non-anticoagulant heparan sulfate to anticoagulant heparan sulfate.
• Tissue Specificity: Ubiquitous. Most abundant in liver and placenta, followed by heart and kidney.
• KEGG Pathway: Glycosaminoglycan biosynthesis - heparan sulfate / heparin (hsa00534)
• Reactome Pathway: HS-GAG biosynthesis (R-HSA-2022928)
• BioCyc Pathway: MetaCyc:HS04884-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
Pancreatic cancer	DISJC981	Strong	Biomarker	[5]
Bladder cancer	DISUHNM0	Limited	Altered Expression	[6]
Endometriosis	DISX1AG8	Limited	Biomarker	[7]
Urinary bladder cancer	DISDV4T7	Limited	Altered Expression	[6]
Urinary bladder neoplasm	DIS7HACE	Limited	Altered Expression	[6]

18 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 Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[16]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[17]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[18]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[19]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[24]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Heparan sulfate glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1).	[20]

References

• [1] Heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3B1 (HS3ST3B1) promotes angiogenesis and proliferation by induction of VEGF in acute myeloid leukemia cells.J Cell Biochem. 2015 Jun;116(6):1101-12. doi: 10.1002/jcb.25066.
• [2] The Pro-Tumoral Activity of Heparan Sulfate 3-O-Sulfotransferase 3B (HS3ST3B) in Breast Cancer MDA-MB-231 Cells Is Dependent on the Expression of Neuropilin-1.Molecules. 2018 Oct 22;23(10):2718. doi: 10.3390/molecules23102718.
• [3] Heparin sulphate D-glucosaminyl 3-O-sulfotransferase 3B1 plays a role in HBV replication.Virology. 2010 Oct 25;406(2):280-5. doi: 10.1016/j.virol.2010.07.030. Epub 2010 Aug 11.
• [4] Heparan sulfate D-glucosamine 3-O-sulfotransferase 3B1 is a novel regulator of transforming growth factor-beta-mediated epithelial-to-mesenchymal transition and regulated by miR-218 in nonsmall cell lung cancer.J Cancer Res Ther. 2018 Jan;14(1):24-29. doi: 10.4103/jcrt.JCRT_659_17.
• [5] Heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3B1, a novel epithelial-mesenchymal transition inducer in pancreatic cancer.Cancer Biol Ther. 2011 Sep 1;12(5):388-98. doi: 10.4161/cbt.12.5.15957. Epub 2011 Sep 1.
• [6] Long Non-coding RNA DLEU1 Promotes Cell Proliferation, Invasion, and Confers Cisplatin Resistance in Bladder Cancer by Regulating the miR-99b/HS3ST3B1 Axis.Front Genet. 2019 Mar 29;10:280. doi: 10.3389/fgene.2019.00280. eCollection 2019.
• [7] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] 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.
• [10] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [11] 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.
• [12] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [13] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [14] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [15] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [16] 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.
• [17] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [18] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [20] 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.
• [21] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [22] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [23] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [25] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.