Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZHUI9T)

• DOT Name: Arylsulfatase K (ARSK)
• Synonyms: ASK; EC 3.1.6.1; Glucuronate-2-sulfatase; EC 3.1.6.18; Telethon sulfatase
• Gene Name: ARSK
• Related Disease: Mucopolysaccharidosis, type 10
• UniProt ID: ARSK_HUMAN
• EC Number: 3.1.6.1; 3.1.6.18
• Pfam ID: PF00884
• Sequence:
  MLLLWVSVVAALALAVLAPGAGEQRRRAAKAPNVVLVVSDSFDGRLTFHPGSQVVKLPFI
  NFMKTRGTSFLNAYTNSPICCPSRAAMWSGLFTHLTESWNNFKGLDPNYTTWMDVMERHG
  YRTQKFGKLDYTSGHHSISNRVEAWTRDVAFLLRQEGRPMVNLIRNRTKVRVMERDWQNT
  DKAVNWLRKEAINYTEPFVIYLGLNLPHPYPSPSSGENFGSSTFHTSLYWLEKVSHDAIK
  IPKWSPLSEMHPVDYYSSYTKNCTGRFTKKEIKNIRAFYYAMCAETDAMLGEIILALHQL
  DLLQKTIVIYSSDHGELAMEHRQFYKMSMYEASAHVPLLMMGPGIKAGLQVSNVVSLVDI
  YPTMLDIAGIPLPQNLSGYSLLPLSSETFKNEHKVKNLHPPWILSEFHGCNVNASTYMLR
  TNHWKYIAYSDGASILPQLFDLSSDPDELTNVAVKFPEITYSLDQKLHSIINYPKVSASV
  HQYNKEQFIKWKQSIGQNYSNVIANLRWHQDWQKEPRKYENAIDQWLKTHMNPRAV
• Function: Catalyzes the hydrolysis of pseudosubstrates such as p-nitrocatechol sulfate and p-nitrophenyl sulfate. Catalyzes the hydrolysis of the 2-sulfate groups of the 2-O-sulfo-D-glucuronate residues of chondroitin sulfate, heparin and heparitin sulfate. Acts selectively on 2-sulfoglucuronate and lacks activity against 2-sulfoiduronate.
• Tissue Specificity: Expressed at high levels in the placenta and pancreas . Expressed at intermediate levels in the lung, brain, heart, liver and kidney and at low levels in the muscle .
• Reactome Pathway:
  Glycosphingolipid catabolism (R-HSA-9840310)
  The activation of arylsulfatases (R-HSA-1663150)

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 10	DISVLZ05	Strong	Autosomal recessive	[1]

10 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 Arylsulfatase K (ARSK).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Arylsulfatase K (ARSK).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Arylsulfatase K (ARSK).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Arylsulfatase K (ARSK).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Arylsulfatase K (ARSK).	[6]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Arylsulfatase K (ARSK).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Arylsulfatase K (ARSK).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Arylsulfatase K (ARSK).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Arylsulfatase K (ARSK).	[10]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Arylsulfatase K (ARSK).	[11]

References

• [1] Novel subtype of mucopolysaccharidosis caused by arylsulfatase K (ARSK) deficiency. J Med Genet. 2022 Oct;59(10):957-964. doi: 10.1136/jmedgenet-2021-108061. Epub 2021 Dec 16.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [9] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [10] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [11] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.