Details of Drug Off-Target (DOT)

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

• DOT Name: Sulfhydryl oxidase 2 (QSOX2)
• Synonyms: EC 1.8.3.2; Neuroblastoma-derived sulfhydryl oxidase; Quiescin Q6-like protein 1
• Gene Name: QSOX2
• Related Disease: Neuroblastoma
• UniProt ID: QSOX2_HUMAN
• EC Number: 1.8.3.2
• Pfam ID: PF04777 ; PF18371 ; PF18108 ; PF00085
• Sequence:
  MAAAGAAVARSPGIGAGPALRARRSPPPRAARLPRLLVLLAAAAVGPGAGGAARLYRAGE
  DAVWVLDSGSVRGATANSSAAWLVQFYSSWCGHCIGYAPTWRALAGDVRDWASAIRVAAL
  DCMEEKNQAVCHDYDIHFYPTFRYFKAFTKEFTTGENFKGPDRELRTVRQTMIDFLQNHT
  EGSRPPACPRLDPIQPSDVLSLLDNRGSHYVAIVFESNSSYLGREVILDLIPYESIVVTR
  ALDGDKAFLEKLGVSSVPSCYLIYPNGSHGLINVVKPLRAFFSSYLKSLPDVRKKSLPLP
  EKPHKEENSEIVVWREFDKSKLYTVDLESGLHYLLRVELAAHKSLAGAELKTLKDFVTVL
  AKLFPGRPPVKKLLEMLQEWLASLPLDRIPYNAVLDLVNNKMRISGIFLTNHIKWVGCQG
  SRSELRGYPCSLWKLFHTLTVEASTHPDALVGTGFEDDPQAVLQTMRRYVHTFFGCKECG
  EHFEEMAKESMDSVKTPDQAILWLWKKHNMVNGRLAGHLSEDPRFPKLQWPTPDLCPACH
  EEIKGLASWDEGHVLTFLKQHYGRDNLLDTYSADQGDSSEGGTLARGEEEEKRLTPPEVS
  HGDRDTQSVRPPGALGPRPALPESLHHSLDGKLQSLDGPGAHKEVGGAAPFLGVDFSSLD
  MSLCVVLYVASSLFLMVMYFFFRVRSRRWKVKHHHPAV
• Function: Catalyzes the oxidation of sulfhydryl groups in peptide and protein thiols to disulfides with the reduction of oxygen to hydrogen peroxide. May contribute to disulfide bond formation in a variety of secreted proteins. Also seems to play a role in regulating the sensitization of neuroblastoma cells for interferon-gamma-induced apoptosis.
• Tissue Specificity: Expressed in pancreas, brain, placenta, kidney, heart and fetal tissues. Weakly expressed in lung, liver and skeletal muscles.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	moderate	Biomarker	[1]

4 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 Sulfhydryl oxidase 2 (QSOX2).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Sulfhydryl oxidase 2 (QSOX2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sulfhydryl oxidase 2 (QSOX2).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Sulfhydryl oxidase 2 (QSOX2).	[8]

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 Sulfhydryl oxidase 2 (QSOX2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Sulfhydryl oxidase 2 (QSOX2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sulfhydryl oxidase 2 (QSOX2).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Sulfhydryl oxidase 2 (QSOX2).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sulfhydryl oxidase 2 (QSOX2).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Sulfhydryl oxidase 2 (QSOX2).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Sulfhydryl oxidase 2 (QSOX2).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Sulfhydryl oxidase 2 (QSOX2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sulfhydryl oxidase 2 (QSOX2).	[6]

References

• [1] Neuroblastoma-derived sulfhydryl oxidase, a new member of the sulfhydryl oxidase/Quiescin6 family, regulates sensitization to interferon gamma-induced cell death in human neuroblastoma cells.Cancer Res. 2003 Nov 15;63(22):7742-52.
• [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] 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.
• [6] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] 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.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [11] 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.