Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8A3H9Y)

DOT Name Heparan-sulfate 6-O-sulfotransferase 2 (HS6ST2)
Synonyms HS6ST-2; EC 2.8.2.-
Gene Name HS6ST2
Related Disease
Paganini-Miozzo syndrome ( )
UniProt ID
H6ST2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.8.2.-
Pfam ID
PF03567
Sequence
MALPACAVREFEPPRQPERGAPVRTTCPRRHSRVEAELAASRPGSVAASVRAGPPRGVSH
GFHTRPLLDKPRKASSSLAGAACAPLFALLSRGRRRRMHVLRRRWDLGSLCRALLTRGLA
ALGHSLKHVLGAIFSKIFGPMASVGNMDEKSNKLLLALVMLFLFAVIVLQYVCPGTECQL
LRLQAFSSPVPDPYRSEDESSARFVPRYNFTRGDLLRKVDFDIKGDDLIVFLHIQKTGGT
TFGRHLVRNIQLEQPCECRVGQKKCTCHRPGKRETWLFSRFSTGWSCGLHADWTELTSCV
PSVVDGKRDARLRPSRNFHYITILRDPVSRYLSEWRHVQRGATWKASLHVCDGRPPTSEE
LPSCYTGDDWSGCPLKEFMDCPYNLANNRQVRMLSDLTLVGCYNLSVMPEKQRNKVLLES
AKSNLKHMAFFGLTEFQRKTQYLFEKTFNMNFISPFTQYNTTRASSVEINEEIQKRIEGL
NFLDMELYSYAKDLFLQRYQFMRQKEHQEARRKRQEQRKFLKGRLLQTHFQSQGQGQSQN
PNQNQSQNPNPNANQNLTQNLMQNLTQSLSQKENRESPKQNSGKEQNDNTSNGTNDYIGS
VEKWR
Function 6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate.
KEGG Pathway
Glycosaminoglycan biosynthesis - heparan sulfate / heparin (hsa00534 )
Reactome Pathway
HS-GAG biosynthesis (R-HSA-2022928 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Paganini-Miozzo syndrome DISOODTR Limited X-linked [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Heparan-sulfate 6-O-sulfotransferase 2 (HS6ST2). [2]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Heparan-sulfate 6-O-sulfotransferase 2 (HS6ST2). [9]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Heparan-sulfate 6-O-sulfotransferase 2 (HS6ST2). [3]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Heparan-sulfate 6-O-sulfotransferase 2 (HS6ST2). [4]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Heparan-sulfate 6-O-sulfotransferase 2 (HS6ST2). [5]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Heparan-sulfate 6-O-sulfotransferase 2 (HS6ST2). [6]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Heparan-sulfate 6-O-sulfotransferase 2 (HS6ST2). [7]
Fluorouracil DMUM7HZ Approved Fluorouracil decreases the expression of Heparan-sulfate 6-O-sulfotransferase 2 (HS6ST2). [8]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Heparan-sulfate 6-O-sulfotransferase 2 (HS6ST2). [6]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Heparan-sulfate 6-O-sulfotransferase 2 (HS6ST2). [10]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Heparan-sulfate 6-O-sulfotransferase 2 (HS6ST2). [11]
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⏷ Show the Full List of 9 Drug(s)

References

1 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
2 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.
3 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
4 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.
5 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
6 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.
7 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
8 Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
9 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.
10 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
11 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.