Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAFFAE8)

DOT Name N-acetylgalactosamine-6-sulfatase (GALNS)
Synonyms EC 3.1.6.4; Chondroitinsulfatase; Chondroitinase; Galactose-6-sulfate sulfatase; GalN6S; N-acetylgalactosamine-6-sulfate sulfatase; GalNAc6S sulfatase
Gene Name GALNS
Related Disease
Mucopolysaccharidosis type 4A ( )
UniProt ID
GALNS_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4FDI; 4FDJ
EC Number
3.1.6.4
Pfam ID
PF00884 ; PF14707
Sequence
MAAVVAATRWWQLLLVLSAAGMGASGAPQPPNILLLLMDDMGWGDLGVYGEPSRETPNLD
RMAAEGLLFPNFYSANPLCSPSRAALLTGRLPIRNGFYTTNAHARNAYTPQEIVGGIPDS
EQLLPELLKKAGYVSKIVGKWHLGHRPQFHPLKHGFDEWFGSPNCHFGPYDNKARPNIPV
YRDWEMVGRYYEEFPINLKTGEANLTQIYLQEALDFIKRQARHHPFFLYWAVDATHAPVY
ASKPFLGTSQRGRYGDAVREIDDSIGKILELLQDLHVADNTFVFFTSDNGAALISAPEQG
GSNGPFLCGKQTTFEGGMREPALAWWPGHVTAGQVSHQLGSIMDLFTTSLALAGLTPPSD
RAIDGLNLLPTLLQGRLMDRPIFYYRGDTLMAATLGQHKAHFWTWTNSWENFRQGIDFCP
GQNVSGVTTHNLEDHTKLPLIFHLGRDPGERFPLSFASAEYQEALSRITSVVQQHQEALV
PAQPQLNVCNWAVMNWAPPGCEKLGKCLTPPESIPKKCLWSH
KEGG Pathway
Glycosaminoglycan degradation (hsa00531 )
Metabolic pathways (hsa01100 )
Lysosome (hsa04142 )
Reactome Pathway
MPS IV - Morquio syndrome A (R-HSA-2206290 )
Neutrophil degranulation (R-HSA-6798695 )
Keratan sulfate degradation (R-HSA-2022857 )
BioCyc Pathway
MetaCyc:HS06790-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Mucopolysaccharidosis type 4A DISTYFQS Definitive Autosomal recessive [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 N-acetylgalactosamine-6-sulfatase (GALNS). [2]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of N-acetylgalactosamine-6-sulfatase (GALNS). [7]
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6 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 N-acetylgalactosamine-6-sulfatase (GALNS). [3]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of N-acetylgalactosamine-6-sulfatase (GALNS). [4]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of N-acetylgalactosamine-6-sulfatase (GALNS). [5]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of N-acetylgalactosamine-6-sulfatase (GALNS). [6]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of N-acetylgalactosamine-6-sulfatase (GALNS). [8]
PP-242 DM2348V Investigative PP-242 decreases the expression of N-acetylgalactosamine-6-sulfatase (GALNS). [9]
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⏷ Show the Full List of 6 Drug(s)

References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
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 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.
4 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
5 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.
6 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
7 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.
8 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.
9 Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.