Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDGV8X3)

• DOT Name: Translation initiation factor eIF2 assembly protein (CDC123)
• Synonyms: Cell division cycle protein 123 homolog; Protein D123; HT-1080; PZ32
• Gene Name: CDC123
• UniProt ID: CD123_HUMAN
• PDB ID: 8PHD; 8PHV
• Pfam ID: PF07065
• Sequence:
  MKKEHVLHCQFSAWYPFFRGVTIKSVILPLPQNVKDYLLDDGTLVVSGRDDPPTHSQPDS
  DDEAEEIQWSDDENTATLTAPEFPEFATKVQEAINSLGGSVFPKLNWSAPRDAYWIAMNS
  SLKCKTLSDIFLLFKSSDFITRDFTQPFIHCTDDSPDPCIEYELVLRKWCELIPGAEFRC
  FVKENKLIGISQRDYTQYYDHISKQKEEIRRCIQDFFKKHIQYKFLDEDFVFDIYRDSRG
  KVWLIDFNPFGEVTDSLLFTWEELISENNLNGDFSEVDAQEQDSPAFRCTNSEVTVQPSP
  YLSYRLPKDFVDLSTGEDAHKLIDFLKLKRNQQEDD
• Function: ATP-dependent protein-folding chaperone for the eIF2 complex. Binds to the gamma subunit of the eIF2 complex which allows the subunit to assemble with the alpha and beta subunits.
• Tissue Specificity: Widely expressed. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon and leukocytes with the highest expression in testis.

Molecular Interaction Atlas (MIA) of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Translation initiation factor eIF2 assembly protein (CDC123).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Translation initiation factor eIF2 assembly protein (CDC123).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Translation initiation factor eIF2 assembly protein (CDC123).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Translation initiation factor eIF2 assembly protein (CDC123).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Translation initiation factor eIF2 assembly protein (CDC123).	[4]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Translation initiation factor eIF2 assembly protein (CDC123).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Translation initiation factor eIF2 assembly protein (CDC123).	[7]

References

• [1] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [2] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.
• [6] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [7] 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.