Details of Drug Off-Target (DOT)

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

• DOT Name: N-sulphoglucosamine sulphohydrolase (SGSH)
• Synonyms: EC 3.10.1.1; Sulfoglucosamine sulfamidase; Sulphamidase
• Gene Name: SGSH
• Related Disease: Mucopolysaccharidosis type 3A
• UniProt ID: SPHM_HUMAN
• PDB ID: 4MHX; 4MIV
• EC Number: 3.10.1.1
• Pfam ID: PF16347 ; PF00884
• Sequence:
  MSCPVPACCALLLVLGLCRARPRNALLLLADDGGFESGAYNNSAIATPHLDALARRSLLF
  RNAFTSVSSCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFDKVRSLPLLLSQAGVRTGI
  IGKKHVGPETVYPFDFAYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRPFFLYVAFHDP
  HRCGHSQPQYGTFCEKFGNGESGMGRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAAQY
  TTVGRMDQGVGLVLQELRDAGVLNDTLVIFTSDNGIPFPSGRTNLYWPGTAEPLLVSSPE
  HPKRWGQVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKTIHLTGRSLLPALEAEPLWAT
  VFGSQSHHEVTMSYPMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTFQDLLNRTTAGQP
  TGWYKDLRHYYYRARWELYDRSRDPHETQNLATDPRFAQLLEMLRDQLAKWQWETHDPWV
  CAPDGVLEEKLSPQCQPLHNEL
• Function: Catalyzes a step in lysosomal heparan sulfate degradation.
• KEGG Pathway:
  Glycosaminoglycan degradation (hsa00531)
  Metabolic pathways (hsa01100)
  Lysosome (hsa04142)
• Reactome Pathway:
  MPS IIIA - Sanfilippo syndrome A (R-HSA-2206307)
  HS-GAG degradation (R-HSA-2024096)

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 3A	DIS2TLNF	Definitive	Autosomal recessive	[1]

9 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 N-sulphoglucosamine sulphohydrolase (SGSH).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of N-sulphoglucosamine sulphohydrolase (SGSH).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of N-sulphoglucosamine sulphohydrolase (SGSH).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of N-sulphoglucosamine sulphohydrolase (SGSH).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of N-sulphoglucosamine sulphohydrolase (SGSH).	[6]
Selenium	DM25CGV	Approved	Selenium increases the expression of N-sulphoglucosamine sulphohydrolase (SGSH).	[8]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of N-sulphoglucosamine sulphohydrolase (SGSH).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of N-sulphoglucosamine sulphohydrolase (SGSH).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of N-sulphoglucosamine sulphohydrolase (SGSH).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of N-sulphoglucosamine sulphohydrolase (SGSH).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of N-sulphoglucosamine sulphohydrolase (SGSH).	[12]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] 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.
• [10] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [11] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [12] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.