Details of Drug Off-Target (DOT)

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

• DOT Name: CD59 glycoprotein (CD59)
• Synonyms: 1F5 antigen; 20 kDa homologous restriction factor; HRF-20; HRF20; MAC-inhibitory protein; MAC-IP; MEM43 antigen; Membrane attack complex inhibition factor; MACIF; Membrane inhibitor of reactive lysis; MIRL; Protectin; CD antigen CD59
• Gene Name: CD59
• Related Disease: Primary CD59 deficiency
• UniProt ID: CD59_HUMAN
• PDB ID: 1CDQ; 1CDR; 1CDS; 1ERG; 1ERH; 2J8B; 2OFS; 2UWR; 2UX2; 4BIK; 5IMT; 5IMY; 6ZD0; 8B0F; 8B0G; 8B0H
• Pfam ID: PF00021
• Sequence:
  MGIQGGSVLFGLLLVLAVFCHSGHSLQCYNCPNPTADCKTAVNCSSDFDACLITKAGLQV
  YNKCWKFEHCNFNDVTTRLRENELTYYCCKKDLCNFNEQLENGGTSLSEKTVLLLVTPFL
  AAAWSLHP
• Function: Potent inhibitor of the complement membrane attack complex (MAC) action. Acts by binding to the C8 and/or C9 complements of the assembling MAC, thereby preventing incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore. This inhibitor appears to be species-specific. Involved in signal transduction for T-cell activation complexed to a protein tyrosine kinase.; The soluble form from urine retains its specific complement binding activity, but exhibits greatly reduced ability to inhibit MAC assembly on cell membranes.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Hematopoietic cell lineage (hsa04640)
• Reactome Pathway:
  Cargo concentration in the ER (R-HSA-5694530)
  Neutrophil degranulation (R-HSA-6798695)
  COPI-mediated anterograde transport (R-HSA-6807878)
  Regulation of Complement cascade (R-HSA-977606)
  COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Primary CD59 deficiency	DISQH167	Strong	Autosomal recessive	[1]

27 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 CD59 glycoprotein (CD59).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of CD59 glycoprotein (CD59).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of CD59 glycoprotein (CD59).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of CD59 glycoprotein (CD59).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CD59 glycoprotein (CD59).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of CD59 glycoprotein (CD59).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of CD59 glycoprotein (CD59).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of CD59 glycoprotein (CD59).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of CD59 glycoprotein (CD59).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of CD59 glycoprotein (CD59).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the mutagenesis of CD59 glycoprotein (CD59).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of CD59 glycoprotein (CD59).	[14]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of CD59 glycoprotein (CD59).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of CD59 glycoprotein (CD59).	[15]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of CD59 glycoprotein (CD59).	[16]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of CD59 glycoprotein (CD59).	[17]
Mitomycin	DMH0ZJE	Approved	Mitomycin increases the mutagenesis of CD59 glycoprotein (CD59).	[18]
Colchicine	DM2POTE	Approved	Colchicine increases the mutagenesis of CD59 glycoprotein (CD59).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of CD59 glycoprotein (CD59).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of CD59 glycoprotein (CD59).	[19]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of CD59 glycoprotein (CD59).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of CD59 glycoprotein (CD59).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of CD59 glycoprotein (CD59).	[22]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of CD59 glycoprotein (CD59).	[23]
Lead acetate	DML0GZ2	Investigative	Lead acetate increases the mutagenesis of CD59 glycoprotein (CD59).	[18]
Buthionine sulfoximine	DMJ46CB	Investigative	Buthionine sulfoximine increases the mutagenesis of CD59 glycoprotein (CD59).	[24]
Ethidium	DMMEQUR	Investigative	Ethidium increases the mutagenesis of CD59 glycoprotein (CD59).	[18]

1 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 CD59 glycoprotein (CD59).	[10]

References

• [1] Paroxysmal nocturnal hemoglobinuria due to hereditary nucleotide deletion in the HRF20 (CD59) gene. Eur J Immunol. 1992 Oct;22(10):2669-73. doi: 10.1002/eji.1830221029.
• [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] 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] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Persistence of cisplatin-induced mutagenicity in hematopoietic stem cells: implications for secondary cancer risk following chemotherapy. Toxicol Sci. 2014 Aug 1;140(2):307-14. doi: 10.1093/toxsci/kfu078. Epub 2014 May 5.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] Mechanisms of the genotoxicity of crocidolite asbestos in mammalian cells: implication from mutation patterns induced by reactive oxygen species. Environ Health Perspect. 2002 Oct;110(10):1003-8. doi: 10.1289/ehp.021101003.
• [14] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [15] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [16] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [17] Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 2008 Aug;23(4):423-34.
• [18] Comparison of the mutagenic potential of 17 physical and chemical agents analyzed by the flow cytometry mutation assay. Mutat Res. 2006 Dec 1;602(1-2):14-25. doi: 10.1016/j.mrfmmm.2006.07.009. Epub 2006 Oct 11.
• [19] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [20] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [21] 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.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [23] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [24] [CD59 mutation and DNA oxidative damage in A(L) cells induced by crocidolite fibers]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2004 Feb;22(1):43-6.