Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGTH90I)

• DOT Name: Cytochrome b-245 chaperone 1 (CYBC1)
• Synonyms: Essential for reactive oxygen species protein; Eros
• Gene Name: CYBC1
• Related Disease:
  Attention deficit hyperactivity disorder
  Colitis
  Granulomatous disease, chronic, autosomal recessive, 5
  Neoplasm of mature B-cells
  Respiratory syncytial virus infection
  Chronic granulomatous disease
• UniProt ID: CYBC1_HUMAN
• Pfam ID: PF15169
• Sequence:
  MYLQVETRTSSRLHLKRAPGIRSWSLLVGILSIGLAAAYYSGDSLGWKLFYVTGCLFVAV
  QNLEDWEEAIFDKSTGKVVLKTFSLYKKLLTLFRAGHDQVVVLLHDVRDVSVEEEKVRYF
  GKGYMVVLRLATGFSHPLTQSAVMGHRSDVEAIAKLITSFLELHCLESPTELSQSSDSEA
  GDPASQS
• Function: Functions as a chaperone necessary for a stable expression of the CYBA and CYBB subunits of the cytochrome b-245 heterodimer. Controls the phagocyte respiratory burst and is essential for innate immunity.
• Tissue Specificity: Highly expressed in macrophages, neutrophils and monocytes.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[1]
Colitis	DISAF7DD	Strong	Biomarker	[2]
Granulomatous disease, chronic, autosomal recessive, 5	DISMSEDG	Strong	Autosomal recessive	[3]
Neoplasm of mature B-cells	DISKAXO0	Strong	Genetic Variation	[4]
Respiratory syncytial virus infection	DIS7FWHY	Strong	Genetic Variation	[5]
Chronic granulomatous disease	DIS9ZR24	Supportive	Autosomal recessive	[2]

1 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 Cytochrome b-245 chaperone 1 (CYBC1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cytochrome b-245 chaperone 1 (CYBC1).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cytochrome b-245 chaperone 1 (CYBC1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cytochrome b-245 chaperone 1 (CYBC1).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cytochrome b-245 chaperone 1 (CYBC1).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cytochrome b-245 chaperone 1 (CYBC1).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cytochrome b-245 chaperone 1 (CYBC1).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Cytochrome b-245 chaperone 1 (CYBC1).	[13]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cytochrome b-245 chaperone 1 (CYBC1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cytochrome b-245 chaperone 1 (CYBC1).	[14]

References

• [1] Early-Onset Efficacy and Safety Pilot Study of Amphetamine Extended-Release Oral Suspension in the Treatment of Children with Attention-Deficit/Hyperactivity Disorder.J Child Adolesc Psychopharmacol. 2019 Feb;29(1):2-8. doi: 10.1089/cap.2018.0078. Epub 2018 Dec 21.
• [2] A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease. Nat Commun. 2018 Oct 25;9(1):4447. doi: 10.1038/s41467-018-06964-x.
• [3] Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity. J Exp Med. 2017 Apr 3;214(4):1111-1128. doi: 10.1084/jem.20161382. Epub 2017 Mar 28.
• [4] Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region.Am J Hum Genet. 2014 Oct 2;95(4):462-71. doi: 10.1016/j.ajhg.2014.09.004.
• [5] Interaction between healthcare professionals and parents is a key determinant of parental distress during childhood hospitalisation for respiratory syncytial virus infection (European RSV Outcomes Study [EROS]).Acta Paediatr. 2018 May;107(5):854-860. doi: 10.1111/apa.14224. Epub 2018 Feb 12.
• [6] 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.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] 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.