Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEJQ9FC)

• DOT Name: Sulfite oxidase, mitochondrial (SUOX)
• Synonyms: EC 1.8.3.1
• Gene Name: SUOX
• Related Disease:
  Isolated sulfite oxidase deficiency
  Alzheimer disease
  Encephalomalacia
  Inborn error of metabolism
  Molybdenum cofactor deficiency
  Prostate cancer
  Prostate carcinoma
  Rheumatoid arthritis
  Type-1 diabetes
  Ankylosing spondylitis
  Autoimmune disease
  Autoimmune disease, susceptibility to, 6
  Autoimmune thyroid disease
  Coeliac disease
  Common variable immunodeficiency
  Crohn disease
  Juvenile idiopathic arthritis
  Psoriasis
  STAT3-related early-onset multisystem autoimmune disease
  Systemic lupus erythematosus
  Ulcerative colitis
  Intellectual disability
• UniProt ID: SUOX_HUMAN
• PDB ID: 1MJ4
• EC Number: 1.8.3.1
• Pfam ID: PF00173 ; PF03404 ; PF00174
• Sequence:
  MLLLHRAVVLRLQQACRLKSIPSRICIQACSTNDSFQPQRPSLTFSGDNSSTQGWRVMGT
  LLGLGAVLAYQDHRCRAAQESTHIYTKEEVSSHTSPETGIWVTLGSEVFDVTEFVDLHPG
  GPSKLMLAAGGPLEPFWALYAVHNQSHVRELLAQYKIGELNPEDKVAPTVETSDPYADDP
  VRHPALKVNSQRPFNAEPPPELLTENYITPNPIFFTRNHLPVPNLDPDTYRLHVVGAPGG
  QSLSLSLDDLHNFPRYEITVTLQCAGNRRSEMTQVKEVKGLEWRTGAISTARWAGARLCD
  VLAQAGHQLCETEAHVCFEGLDSDPTGTAYGASIPLARAMDPEAEVLLAYEMNGQPLPRD
  HGFPVRVVVPGVVGARHVKWLGRVSVQPEESYSHWQRRDYKGFSPSVDWETVDFDSAPSI
  QELPVQSAITEPRDGETVESGEVTIKGYAWSGGGRAVIRVDVSLDGGLTWQVAKLDGEEQ
  RPRKAWAWRLWQLKAPVPAGQKELNIVCKAVDDGYNVQPDTVAPIWNLRGVLSNAWHRVH
  VYVSP
• Function: Catalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.
• KEGG Pathway:
  Sulfur metabolism (hsa00920)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Sulfide oxidation to sulfate (R-HSA-1614517)
• BioCyc Pathway: MetaCyc:HS06627-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

22 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Isolated sulfite oxidase deficiency	DISQ9TGT	Definitive	Autosomal recessive	[1]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[2]
Encephalomalacia	DISDJXKJ	Strong	Biomarker	[3]
Inborn error of metabolism	DISO5FAY	Strong	Genetic Variation	[4]
Molybdenum cofactor deficiency	DISKS8QN	Strong	Biomarker	[5]
Prostate cancer	DISF190Y	Strong	Altered Expression	[6]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[6]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[7]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[8]
Ankylosing spondylitis	DISRC6IR	moderate	Genetic Variation	[8]
Autoimmune disease	DISORMTM	moderate	Genetic Variation	[8]
Autoimmune disease, susceptibility to, 6	DISHNUXI	moderate	Genetic Variation	[8]
Autoimmune thyroid disease	DISIHC6A	moderate	Genetic Variation	[8]
Coeliac disease	DISIY60C	moderate	Genetic Variation	[8]
Common variable immunodeficiency	DISHE7JQ	moderate	Genetic Variation	[8]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[8]
Juvenile idiopathic arthritis	DISQZGBV	moderate	Genetic Variation	[8]
Psoriasis	DIS59VMN	moderate	Genetic Variation	[8]
STAT3-related early-onset multisystem autoimmune disease	DISAXTN7	moderate	Genetic Variation	[8]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[8]
Ulcerative colitis	DIS8K27O	moderate	Genetic Variation	[8]
Intellectual disability	DISMBNXP	Disputed	Altered Expression	[9]

13 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Sulfite oxidase, mitochondrial (SUOX).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Sulfite oxidase, mitochondrial (SUOX).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sulfite oxidase, mitochondrial (SUOX).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sulfite oxidase, mitochondrial (SUOX).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sulfite oxidase, mitochondrial (SUOX).	[14]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Sulfite oxidase, mitochondrial (SUOX).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Sulfite oxidase, mitochondrial (SUOX).	[16]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sulfite oxidase, mitochondrial (SUOX).	[17]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Sulfite oxidase, mitochondrial (SUOX).	[18]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Sulfite oxidase, mitochondrial (SUOX).	[18]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Sulfite oxidase, mitochondrial (SUOX).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Sulfite oxidase, mitochondrial (SUOX).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Sulfite oxidase, mitochondrial (SUOX).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Sulfite oxidase, mitochondrial (SUOX).	[20]

References

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• [2] A disease-modifying treatment for Alzheimer's disease: focus on the trans-sulfuration pathway.Rev Neurosci. 2020 Apr 28;31(3):319-334. doi: 10.1515/revneuro-2019-0076.
• [3] Functional deficiencies of sulfite oxidase: Differential diagnoses in neonates presenting with intractable seizures and cystic encephalomalacia.Brain Dev. 2010 Aug;32(7):544-9. doi: 10.1016/j.braindev.2009.09.005. Epub 2009 Sep 29.
• [4] Prenatal diagnosis of molybdenum cofactor deficiency and isolated sulfite oxidase deficiency.Prenat Diagn. 2003 Jan;23(1):6-8. doi: 10.1002/pd.505.
• [5] Antenatal manifestations of inborn errors of metabolism: autopsy findings suggestive of a metabolic disorder.J Inherit Metab Dis. 2016 Sep;39(5):597-610. doi: 10.1007/s10545-016-9937-x. Epub 2016 Apr 22.
• [6] High sulfite oxidase expression could predict postoperative biochemical recurrence in patients with prostate cancer.Med Mol Morphol. 2019 Sep;52(3):164-172. doi: 10.1007/s00795-018-00214-1. Epub 2019 Jan 10.
• [7] Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.Hum Mol Genet. 2019 Mar 1;28(5):858-874. doi: 10.1093/hmg/ddy395.
• [8] Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.Nat Med. 2015 Sep;21(9):1018-27. doi: 10.1038/nm.3933. Epub 2015 Aug 24.
• [9] Molybdenum cofactor deficiency: Identification of a patient with homozygote mutation in the MOCS3 gene.Am J Med Genet A. 2017 Jun;173(6):1601-1606. doi: 10.1002/ajmg.a.38240.
• [10] 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.
• [11] 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.
• [12] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [13] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [16] 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.
• [17] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [18] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [19] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [20] 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.
• [21] 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.
• [22] 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.