Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYPPL5X)

• DOT Name: Cytosolic iron-sulfur assembly component 2A (CIAO2A)
• Synonyms: MIP18 family protein FAM96A
• Gene Name: CIAO2A
• Related Disease:
  Gastrointestinal stromal tumour
  Hepatocellular carcinoma
  Neoplasm
  Colitis
• UniProt ID: CIA2A_HUMAN
• PDB ID: 2M5H; 3UX2; 3UX3
• Pfam ID: PF01883
• Sequence:
  MQRVSGLLSWTLSRVLWLSGLSEPGAARQPRIMEEKALEVYDLIRTIRDPEKPNTLEELE
  VVSESCVEVQEINEEEYLVIIRFTPTVPHCSLATLIGLCLRVKLQRCLPFKHKLEIYISE
  GTHSTEEDINKQINDKERVAAAMENPNLREIVEQCVLEPD
• 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 specifically matures ACO1 and stabilizes IREB2, connecting cytosolic iron-sulfur protein maturation with cellular iron regulation. May play a role in chromosome segregation through establishment of sister chromatid cohesion. May induce apoptosis in collaboration with APAF1.
• Tissue Specificity: Substantially enriched in macrophages.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastrointestinal stromal tumour	DIS6TJYS	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Colitis	DISAF7DD	moderate	Biomarker	[1]

8 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 Cytosolic iron-sulfur assembly component 2A (CIAO2A).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytosolic iron-sulfur assembly component 2A (CIAO2A).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cytosolic iron-sulfur assembly component 2A (CIAO2A).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cytosolic iron-sulfur assembly component 2A (CIAO2A).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cytosolic iron-sulfur assembly component 2A (CIAO2A).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cytosolic iron-sulfur assembly component 2A (CIAO2A).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cytosolic iron-sulfur assembly component 2A (CIAO2A).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cytosolic iron-sulfur assembly component 2A (CIAO2A).	[10]

References

• [1] FAM96A Protects Mice From Dextran Sulfate Sodium (DSS)-Induced Colitis by Preventing Microbial Dysbiosis.Front Cell Infect Microbiol. 2019 Nov 18;9:381. doi: 10.3389/fcimb.2019.00381. eCollection 2019.
• [2] Combination therapy of hTERTR and FAM96A for hepatocellular carcinoma through enhancing apoptosis sensitivity.Exp Ther Med. 2018 Jan;15(1):641-648. doi: 10.3892/etm.2017.5505. Epub 2017 Nov 13.
• [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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.