Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0MM1MW)

• DOT Name: CDGSH iron-sulfur domain-containing protein 3, mitochondrial (CISD3)
• Synonyms: MitoNEET-related protein 2; Miner2; Mitochondrial inner NEET protein; MiNT
• Gene Name: CISD3
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Colonic neoplasm
  Colorectal carcinoma
  Cryohydrocytosis
  Familial adenomatous polyposis
  Hepatocellular carcinoma
  Hereditary nonpolyposis colon cancer
  Melanoma
  Neoplasm
  Renal cell carcinoma
  Non-insulin dependent diabetes
  Wolfram syndrome 2
  Non-small-cell lung cancer
  Urinary bladder cancer
• UniProt ID: CISD3_HUMAN
• PDB ID: 6AVJ
• Pfam ID: PF09360
• Sequence:
  MRGAGAILRPAARGARDLNPRRDISSWLAQWFPRTPARSVVALKTPIKVELVAGKTYRWC
  VCGRSKKQPFCDGSHFFQRTGLSPLKFKAQETRMVALCTCKATQRPPYCDGTHRSERVQK
  AEVGSPL
• Function: Can transfer its iron-sulfur clusters to the apoferrodoxins FDX1 and FDX2. Contributes to mitochondrial iron homeostasis and in maintaining normal levels of free iron and reactive oxygen species, and thereby contributes to normal mitochondrial function.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Cryohydrocytosis	DISMQHL3	Strong	Genetic Variation	[5]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[5]
Hereditary nonpolyposis colon cancer	DISPA49R	Strong	Posttranslational Modification	[7]
Melanoma	DIS1RRCY	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[9]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[9]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Biomarker	[10]
Wolfram syndrome 2	DISEO4HZ	moderate	Biomarker	[10]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Genetic Variation	[11]
Urinary bladder cancer	DISDV4T7	Disputed	Genetic Variation	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of CDGSH iron-sulfur domain-containing protein 3, mitochondrial (CISD3).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of CDGSH iron-sulfur domain-containing protein 3, mitochondrial (CISD3).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of CDGSH iron-sulfur domain-containing protein 3, mitochondrial (CISD3).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of CDGSH iron-sulfur domain-containing protein 3, mitochondrial (CISD3).	[15]

References

• [1] Structure of the human monomeric NEET protein MiNT and its role in regulating iron and reactive oxygen species in cancer cells.Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):272-277. doi: 10.1073/pnas.1715842115. Epub 2017 Dec 19.
• [2] Open-closed motion of Mint2 regulates APP metabolism.J Mol Cell Biol. 2013 Feb;5(1):48-56. doi: 10.1093/jmcb/mjs033. Epub 2012 Jun 21.
• [3] Oncogenetic tree model of somatic mutations and DNA methylation in colon tumors.Genes Chromosomes Cancer. 2009 Jan;48(1):1-9. doi: 10.1002/gcc.20614.
• [4] 18q loss of heterozygosity in microsatellite stable colorectal cancer is correlated with CpG island methylator phenotype-negative (CIMP-0) and inversely with CIMP-low and CIMP-high.BMC Cancer. 2007 May 2;7:72. doi: 10.1186/1471-2407-7-72.
• [5] Characteristic patterns of altered DNA methylation predict emergence of human hepatocellular carcinoma.Hepatology. 2012 Sep;56(3):994-1003. doi: 10.1002/hep.25706. Epub 2012 Aug 2.
• [6] Epigenetic-genetic interactions in the APC/WNT, RAS/RAF, and P53 pathways in colorectal carcinoma.Clin Cancer Res. 2008 May 1;14(9):2560-9. doi: 10.1158/1078-0432.CCR-07-1802.
• [7] Promoter hypermethylation frequency and BRAF mutations distinguish hereditary non-polyposis colon cancer from sporadic MSI-H colon cancer.Fam Cancer. 2004;3(2):101-7. doi: 10.1023/B:FAME.0000039861.30651.c8.
• [8] Downregulation of microRNA-29c is associated with hypermethylation of tumor-related genes and disease outcome in cutaneous melanoma.Epigenetics. 2011 Mar;6(3):388-94. doi: 10.4161/epi.6.3.14056. Epub 2011 Mar 1.
• [9] Genetic clustering of clear cell renal cell carcinoma based on array-comparative genomic hybridization: its association with DNA methylation alteration and patient outcome.Clin Cancer Res. 2008 Sep 1;14(17):5531-9. doi: 10.1158/1078-0432.CCR-08-0443.
• [10] Binding of Nitric Oxide in CDGSH-type [2Fe-2S] Clusters of the Human Mitochondrial Protein Miner2.J Biol Chem. 2017 Feb 24;292(8):3146-3153. doi: 10.1074/jbc.M116.766774. Epub 2017 Jan 12.
• [11] Examination of a CpG island methylator phenotype and implications of methylation profiles in solid tumors.Cancer Res. 2006 Nov 1;66(21):10621-9. doi: 10.1158/0008-5472.CAN-06-1687.
• [12] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [13] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.