Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTICRN6N)

• DOT Name: Cytosolic iron-sulfur assembly component 2B (CIAO2B)
• Synonyms: MSS19-interacting protein of 18 kDa; Mitotic spindle-associated MMXD complex subunit MIP18; Protein FAM96B
• Gene Name: CIAO2B
• Related Disease: Xeroderma pigmentosum group D
• UniProt ID: CIA2B_HUMAN
• Pfam ID: PF01883
• Sequence:
  MVGGGGVGGGLLENANPLIYQRSGERPVTAGEEDEQVPDSIDAREIFDLIRSINDPEHPL
  TLEELNVVEQVRVQVSDPESTVAVAFTPTIPHCSMATLIGLSIKVKLLRSLPQRFKMDVH
  ITPGTHASEHAVNKQLADKERVAAALENTHLLEVVNQCLSARS
• Function: 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 and in collaboration with CIAO1 and MMS19, binds to and facilitates the assembly of most cytosolic-nuclear Fe/S proteins. As part of the mitotic spindle-associated MMXD complex it plays a role in chromosome segregation, probably by facilitating iron-sulfur cluster assembly into ERCC2/XPD. Together with MMS19, facilitates the transfer of Fe-S clusters to the motor protein KIF4A, which ensures proper localization of KIF4A to mitotic machinery components to promote the progression of mitosis.
• Reactome Pathway: Cytosolic iron-sulfur cluster assembly (R-HSA-2564830)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Xeroderma pigmentosum group D	DISFFE93	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Cytosolic iron-sulfur assembly component 2B (CIAO2B).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cytosolic iron-sulfur assembly component 2B (CIAO2B).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cytosolic iron-sulfur assembly component 2B (CIAO2B).	[4]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Cytosolic iron-sulfur assembly component 2B (CIAO2B).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cytosolic iron-sulfur assembly component 2B (CIAO2B).	[6]

References

• [1] MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome segregation.Mol Cell. 2010 Aug 27;39(4):632-40. doi: 10.1016/j.molcel.2010.07.029.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] 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.
• [5] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [6] 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.