Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT21PY3J)

DOT Name Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2 (NDST2)
Synonyms EC 2.8.2.8; Glucosaminyl N-deacetylase/N-sulfotransferase 2; NDST-2; N-heparan sulfate sulfotransferase 2; N-HSST 2
Gene Name NDST2
Related Disease
Prostate cancer ( )
Prostate neoplasm ( )
Schizophrenia ( )
UniProt ID
NDST2_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.-; 2.8.2.8; 3.-.-.-
Pfam ID
PF12062 ; PF00685
Sequence
MLQLWKVVRPARQLELHRLILLLIAFSLGSMGFLAYYVSTSPKAKEPLPLPLGDCSSGGA
AGPGPARPPVPPRPPRPPETARTEPVVLVFVESAYSQLGQEIVAILESSRFRYSTELAPG
RGDMPTLTDNTHGRYVLVIYENLLKYVNLDAWSRELLDRYCVEYGVGIIGFFRAHEHSLL
SAQLKGFPLFLHSNLGLRDYQVNPSAPLLHLTRPSRLEPGPLPGDDWTIFQSNHSTYEPV
LLASLRPAEPAVPGPVLRRARLPTVVQDLGLHDGIQRVLFGHGLSFWLHKLIFVDAVAYL
TGKRLCLDLDRYILVDIDDIFVGKEGTRMKVADVEALLTTQNKLRTLVPNFTFNLGFSGK
FYHTGTEEEDAGDDMLLKHRKEFWWFPHMWSHMQPHLFHNRSVLADQMRLNKQFALEHGI
PTDLGYAVAPHHSGVYPIHTQLYEAWKSVWGIQVTSTEEYPHLRPARYRRGFIHNGIMVL
PRQTCGLFTHTIFYNEYPGGSRELDRSIRGGELFLTVLLNPISIFMTHLSNYGNDRLGLY
TFESLVRFLQCWTRLRLQTLPPVPLAQKYFELFPQERSPLWQNPCDDKRHKDIWSKEKTC
DRLPKFLIVGPQKTGTTAIHFFLSLHPAVTSSFPSPSTFEEIQFFNSPNYHKGIDWYMDF
FPVPSNASTDFLFEKSATYFDSEVVPRRGAALLPRAKIITVLTNPADRAYSWYQHQRAHG
DPVALNYTFYQVISASSQTPLALRSLQNRCLVPGYYSTHLQRWLTYYPSGQLLIVDGQEL
RTNPAASMESIQKFLGITPFLNYTRTLRFDDDKGFWCQGLEGGKTRCLGRSKGRRYPDMD
TESRLFLTDFFRNHNLELSKLLSRLGQPVPSWLREELQHSSLG
Function
Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan, a prerequisite substrate for later modifications in heparin biosynthesis. Plays a role in determining the extent and pattern of sulfation of heparan sulfate. Required for the exosomal release of SDCBP, CD63 and syndecan.
KEGG Pathway
Glycosaminoglycan biosynthesis - heparan sulfate / heparin (hsa00534 )
Metabolic pathways (hsa01100 )
Reactome Pathway
HS-GAG biosynthesis (R-HSA-2022928 )
BioCyc Pathway
MetaCyc:HS09410-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
Prostate cancer DISF190Y Strong Biomarker [1]
Prostate neoplasm DISHDKGQ Strong Biomarker [1]
Schizophrenia DISSRV2N No Known Unknown [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2 (NDST2). [3]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen affects the expression of Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2 (NDST2). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2 (NDST2). [5]
Aspirin DM672AH Approved Aspirin increases the expression of Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2 (NDST2). [6]
Sulindac DM2QHZU Approved Sulindac decreases the expression of Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2 (NDST2). [6]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2 (NDST2). [7]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 2 (NDST2). [8]
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⏷ Show the Full List of 6 Drug(s)

References

1 The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
2 Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia. Nat Neurosci. 2016 Nov;19(11):1433-1441. doi: 10.1038/nn.4402. Epub 2016 Oct 3.
3 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.
4 Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors. Toxicol In Vitro. 2015 Sep;29(6):1231-9. doi: 10.1016/j.tiv.2014.10.012. Epub 2014 Oct 24.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
7 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.
8 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.