Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDOMP80)

DOT Name	Eukaryotic translation initiation factor 3 subunit D (EIF3D)
Synonyms	eIF3d; Eukaryotic translation initiation factor 3 subunit 7; eIF-3-zeta; eIF3 p66
Gene Name	EIF3D
Related Disease	Breast cancer ( ) Breast carcinoma ( ) Acute myelogenous leukaemia ( ) Bladder cancer ( ) Clear cell renal carcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) Colorectal carcinoma ( ) Glioma ( ) HIV infectious disease ( ) Immunodeficiency ( ) leukaemia ( ) Leukemia ( ) Non-small-cell lung cancer ( ) Renal cell carcinoma ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Advanced cancer ( ) Gastric cancer ( ) Nasopharyngeal carcinoma ( ) Stomach cancer ( ) Hepatocellular carcinoma ( ) Gallbladder cancer ( ) Gallbladder carcinoma ( ) Melanoma ( ) Neoplasm ( ) Prostate cancer ( ) Prostate carcinoma ( )
UniProt ID	EIF3D_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	6YBD; 6YBS; 6ZMW; 6ZON; 6ZP4; 6ZVJ; 7A09; 7QP6; 7QP7; 8PPL
Pfam ID	PF05091
Sequence	MAKFMTPVIQDNPSGWGPCAVPEQFRDMPYQPFSKGDRLGKVADWTGATYQDKRYTNKYS SQFGGGSQYAYFHEEDESSFQLVDTARTQKTAYQRNRMRFAQRNLRRDKDRRNMLQFNLQ ILPKSAKQKERERIRLQKKFQKQFGVRQKWDQKSQKPRDSSVEVRSDWEVKEEMDFPQLM KMRYLEVSEPQDIECCGALEYYDKAFDRITTRSEKPLRSIKRIFHTVTTTDDPVIRKLAK TQGNVFATDAILATLMSCTRSVYSWDIVVQRVGSKLFFDKRDNSDFDLLTVSETANEPPQ DEGNSFNSPRNLAMEATYINHNFSQQCLRMGKERYNFPNPNPFVEDDMDKNEIASVAYRY RRWKLGDDIDLIVRCEHDGVMTGANGEVSFINIKTLNEWDSRHCNGVDWRQKLDSQRGAV IATELKNNSYKLARWTCCALLAGSEYLKLGYVSRYHVKDSSRHVILGTQQFKPNEFASQI NLSVENAWGILRCVIDICMKLEEGKYLILKDPNKQVIRVYSLPDGTFSSDEDEEEEEEEE EEEEEEET
Function	mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, a complex required for several steps in the initiation of protein synthesis of a specialized repertoire of mRNAs. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression. In the eIF-3 complex, EIF3D specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs ; (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2.
Reactome Pathway	Translation initiation complex formation (R-HSA-72649 ) Formation of a pool of free 40S subunits (R-HSA-72689 ) Formation of the ternary complex, and subsequently, the 43S complex (R-HSA-72695 ) Ribosomal scanning and start codon recognition (R-HSA-72702 ) GTP hydrolysis and joining of the 60S ribosomal subunit (R-HSA-72706 ) L13a-mediated translational silencing of Ceruloplasmin expression (R-HSA-156827 )

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Breast cancer	DIS7DPX1	Definitive	Biomarker	[1]
Breast carcinoma	DIS2UE88	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Bladder cancer	DISUHNM0	Strong	Biomarker	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[6]
Glioma	DIS5RPEH	Strong	Biomarker	[7]
HIV infectious disease	DISO97HC	Strong	Biomarker	[8]
Immunodeficiency	DIS093I0	Strong	Biomarker	[8]
leukaemia	DISS7D1V	Strong	Biomarker	[2]
Leukemia	DISNAKFL	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[9]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[4]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[3]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[10]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[11]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[12]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[11]
Hepatocellular carcinoma	DIS0J828	Disputed	Biomarker	[10]
Gallbladder cancer	DISXJUAF	Limited	Biomarker	[13]
Gallbladder carcinoma	DISD6ACL	Limited	Biomarker	[13]
Melanoma	DIS1RRCY	Limited	Biomarker	[14]
Neoplasm	DISZKGEW	Limited	Altered Expression	[4]
Prostate cancer	DISF190Y	Limited	Biomarker	[15]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[15]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Eukaryotic translation initiation factor 3 subunit D (EIF3D).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Eukaryotic translation initiation factor 3 subunit D (EIF3D).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Eukaryotic translation initiation factor 3 subunit D (EIF3D).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Eukaryotic translation initiation factor 3 subunit D (EIF3D).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Eukaryotic translation initiation factor 3 subunit D (EIF3D).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Eukaryotic translation initiation factor 3 subunit D (EIF3D).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Eukaryotic translation initiation factor 3 subunit D (EIF3D).	[23]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Eukaryotic translation initiation factor 3 subunit D (EIF3D).	[24]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Eukaryotic translation initiation factor 3 subunit D (EIF3D).	[25]
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⏷ Show the Full List of 9 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Eukaryotic translation initiation factor 3 subunit D (EIF3D).	[21]
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References

1	Knockdown of eIF3D inhibits breast cancer cell proliferation and invasion through suppressing the Wnt/-catenin signaling pathway.Int J Clin Exp Pathol. 2015 Sep 1;8(9):10420-7. eCollection 2015.
2	Knockdown of eukaryotic translation initiation factor 3 subunit D (eIF3D) inhibits proliferation of acute myeloid leukemia cells.Mol Cell Biochem. 2018 Jan;438(1-2):191-198. doi: 10.1007/s11010-017-3127-5. Epub 2017 Aug 12.
3	Proteomics analysis of bladder cancer invasion: Targeting EIF3D for therapeutic intervention.Oncotarget. 2017 Apr 20;8(41):69435-69455. doi: 10.18632/oncotarget.17279. eCollection 2017 Sep 19.
4	EIF3D promotes sunitinib resistance of renal cell carcinoma by interacting with GRP78 and inhibiting its degradation.EBioMedicine. 2019 Nov;49:189-201. doi: 10.1016/j.ebiom.2019.10.030. Epub 2019 Oct 26.
5	hmiR-34c-3p upregulation inhibits the proliferation of colon cancer cells by targeting EIF3D.Anticancer Drugs. 2018 Nov;29(10):975-982. doi: 10.1097/CAD.0000000000000674.
6	Lentivirus-mediated knockdown of eukaryotic translation initiation factor 3 subunit D inhibits proliferation of HCT116 colon cancer cells.Biosci Rep. 2014 Dec 12;34(6):e00161. doi: 10.1042/BSR20140078.
7	RNAi-Mediated Silencing of EIF3D Alleviates Proliferation and Migration of Glioma U251 and U87MG Cells.Chem Biol Drug Des. 2015 Oct;86(4):715-22. doi: 10.1111/cbdd.12542. Epub 2015 Jul 28.
8	Reduced eIF3d accelerates HIV disease progression by attenuating CD8+ T cell function.J Transl Med. 2019 May 22;17(1):167. doi: 10.1186/s12967-019-1925-0.
9	Correction to: Expression of Concern: Knockdown of eIF3d inhibits cell proliferation through G2/M phase arrest in non-small cell lung cancer.Med Oncol. 2019 May 3;36(6):53. doi: 10.1007/s12032-019-1276-y.
10	Cullin-3/KCTD10 complex is essential for K27-polyubiquitination of EIF3D in human hepatocellular carcinoma HepG2 cells.Biochem Biophys Res Commun. 2019 Sep 3;516(4):1116-1122. doi: 10.1016/j.bbrc.2019.07.010. Epub 2019 Jul 5.
11	High expression of eIF3d is associated with poor prognosis in patients with gastric cancer.Cancer Manag Res. 2017 Oct 25;9:539-544. doi: 10.2147/CMAR.S142324. eCollection 2017.
12	Selection of reliable reference genes for gene expression study in nasopharyngeal carcinoma.Acta Pharmacol Sin. 2010 Nov;31(11):1487-94. doi: 10.1038/aps.2010.115.
13	EIF3D promotes gallbladder cancer development by stabilizing GRK2 kinase and activating PI3K-AKT signaling pathway.Cell Death Dis. 2017 Jun 8;8(6):e2868. doi: 10.1038/cddis.2017.263.
14	Knockdown of EIF3D suppresses proliferation of human melanoma cells through G2/M phase arrest.Biotechnol Appl Biochem. 2015 Sep-Oct;62(5):615-20. doi: 10.1002/bab.1305. Epub 2015 Jan 12.
15	The oncogenic role of EIF3D is associated with increased cell cycle progression and motility in prostate cancer.Med Oncol. 2015 Jul;32(7):518. doi: 10.1007/s12032-015-0518-x. Epub 2015 Jun 3.
16	The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
17	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.
18	Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
19	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.
20	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.
21	Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
22	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.
23	Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
24	Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
25	ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.