Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCU8PFI)

• DOT Name: Probable cytosolic iron-sulfur protein assembly protein CIAO1 (CIAO1)
• Synonyms: WD repeat-containing protein 39
• Gene Name: CIAO1
• Related Disease:
  Rheumatoid arthritis
  Type-1/2 diabetes
• UniProt ID: CIAO1_HUMAN
• PDB ID: 3FM0
• Pfam ID: PF00400
• Sequence:
  MKDSLVLLGRVPAHPDSRCWFLAWNPAGTLLASCGGDRRIRIWGTEGDSWICKSVLSEGH
  QRTVRKVAWSPCGNYLASASFDATTCIWKKNQDDFECVTTLEGHENEVKSVAWAPSGNLL
  ATCSRDKSVWVWEVDEEDEYECVSVLNSHTQDVKHVVWHPSQELLASASYDDTVKLYREE
  EDDWVCCATLEGHESTVWSLAFDPSGQRLASCSDDRTVRIWRQYLPGNEQGVACSGSDPS
  WKCICTLSGFHSRTIYDIAWCQLTGALATACGDDAIRVFQEDPNSDPQQPTFSLTAHLHQ
  AHSQDVNCVAWNPKEPGLLASCSDDGEVAFWKYQRPEGL
• Function: Key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into extramitochondrial Fe/S proteins. As a CIA complex component, interacts specifically with CIAO2A or CIAO2B and MMS19 to assist different branches of iron-sulfur protein assembly, depending of its interactors. The complex CIAO1:CIAO2B:MMS19 binds to and facilitates the assembly of most cytosolic-nuclear Fe/S proteins. CIAO1:CIAO2A specifically matures ACO1 and stabilizes IREB2. Seems to specifically modulate the transactivation activity of WT1. As part of the mitotic spindle-associated MMXD complex it may play a role in chromosome segregation.
• Reactome Pathway: Cytosolic iron-sulfur cluster assembly (R-HSA-2564830)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[1]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Probable cytosolic iron-sulfur protein assembly protein CIAO1 (CIAO1) affects the response to substance of Fluorouracil.	[8]

5 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 Probable cytosolic iron-sulfur protein assembly protein CIAO1 (CIAO1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Probable cytosolic iron-sulfur protein assembly protein CIAO1 (CIAO1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Probable cytosolic iron-sulfur protein assembly protein CIAO1 (CIAO1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Probable cytosolic iron-sulfur protein assembly protein CIAO1 (CIAO1).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Probable cytosolic iron-sulfur protein assembly protein CIAO1 (CIAO1).	[6]

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 decreases the methylation of Probable cytosolic iron-sulfur protein assembly protein CIAO1 (CIAO1).	[7]

References

• [1] Localization of quantitative trait loci regulating adjuvant-induced arthritis in rats: evidence for genetic factors common to multiple autoimmune diseases.J Immunol. 1998 Oct 15;161(8):4411-9.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving pathways and tumor-initiating cells. Nat Commun. 2018 Aug 9;9(1):3069. doi: 10.1038/s41467-018-05402-2.
• [7] 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.
• [8] Mechanistic and predictive profiling of 5-Fluorouracil resistance in human cancer cells. Cancer Res. 2004 Nov 15;64(22):8167-76. doi: 10.1158/0008-5472.CAN-04-0970.