General Information of Drug Off-Target (DOT) (ID: OTFABY9G)

DOT Name Eukaryotic translation initiation factor 3 subunit A (EIF3A)
Synonyms eIF3a; Eukaryotic translation initiation factor 3 subunit 10; eIF-3-theta; eIF3 p167; eIF3 p180; eIF3 p185
Gene Name EIF3A
Related Disease
Acute myelogenous leukaemia ( )
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive ( )
Lung adenocarcinoma ( )
Prostate cancer ( )
Adenocarcinoma ( )
Adult glioblastoma ( )
Amyloidosis ( )
Astrocytoma ( )
Bone osteosarcoma ( )
Brain neoplasm ( )
Breast neoplasm ( )
Carcinoma ( )
Chronic hepatitis B virus infection ( )
Colorectal carcinoma ( )
Epithelial ovarian cancer ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
leukaemia ( )
Leukemia ( )
Lung cancer ( )
Lung carcinoma ( )
Metastatic malignant neoplasm ( )
Myopathy ( )
Nasopharyngeal carcinoma ( )
Osteosarcoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Pulmonary fibrosis ( )
Renal fibrosis ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
Autism ( )
Bladder cancer ( )
Cervical carcinoma ( )
Head-neck squamous cell carcinoma ( )
Intellectual disability ( )
Neurodevelopmental disorder ( )
Urinary bladder cancer ( )
Acute lymphocytic leukaemia ( )
Invasive ductal breast carcinoma ( )
Non-small-cell lung cancer ( )
Parkinson disease ( )
UniProt ID
EIF3A_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
3J8B; 3J8C; 6YBD; 6YBT; 6ZMW; 6ZON; 6ZP4; 6ZVJ; 7A09; 7QP6; 7QP7; 8PPL
Pfam ID
PF01399
Sequence
MPAYFQRPENALKRANEFLEVGKKQPALDVLYDVMKSKKHRTWQKIHEPIMLKYLELCVD
LRKSHLAKEGLYQYKNICQQVNIKSLEDVVRAYLKMAEEKTEAAKEESQQMVLDIEDLDN
IQTPESVLLSAVSGEDTQDRTDRLLLTPWVKFLWESYRQCLDLLRNNSRVERLYHDIAQQ
AFKFCLQYTRKAEFRKLCDNLRMHLSQIQRHHNQSTAINLNNPESQSMHLETRLVQLDSA
ISMELWQEAFKAVEDIHGLFSLSKKPPKPQLMANYYNKVSTVFWKSGNALFHASTLHRLY
HLSREMRKNLTQDEMQRMSTRVLLATLSIPITPERTDIARLLDMDGIIVEKQRRLATLLG
LQAPPTRIGLINDMVRFNVLQYVVPEVKDLYNWLEVEFNPLKLCERVTKVLNWVREQPEK
EPELQQYVPQLQNNTILRLLQQVSQIYQSIEFSRLTSLVPFVDAFQLERAIVDAARHCDL
QVRIDHTSRTLSFGSDLNYATREDAPIGPHLQSMPSEQIRNQLTAMSSVLAKALEVIKPA
HILQEKEEQHQLAVTAYLKNSRKEHQRILARRQTIEERKERLESLNIQREKEELEQREAE
LQKVRKAEEERLRQEAKEREKERILQEHEQIKKKTVRERLEQIKKTELGAKAFKDIDIED
LEELDPDFIMAKQVEQLEKEKKELQERLKNQEKKIDYFERAKRLEEIPLIKSAYEEQRIK
DMDLWEQQEEERITTMQLEREKALEHKNRMSRMLEDRDLFVMRLKAARQSVYEEKLKQFE
ERLAEERHNRLEERKRQRKEERRITYYREKEEEEQRRAEEQMLKEREERERAERAKREEE
LREYQERVKKLEEVERKKRQRELEIEERERRREEERRLGDSSLSRKDSRWGDRDSEGTWR
KGPEADSEWRRGPPEKEWRRGEGRDEDRSHRRDEERPRRLGDDEDREPSLRPDDDRVPRR
GMDDDRGPRRGPEEDRFSRRGADDDRPSWRNTDDDRPPRRIADEDRGNWRHADDDRPPRR
GLDEDRGSWRTADEDRGPRRGMDDDRGPRRGGADDERSSWRNADDDRGPRRGLDDDRGPR
RGMDDDRGPRRGMDDDRGPRRGMDDDRGPRRGLDDDRGPWRNADDDRIPRRGAEDDRGPW
RNMDDDRLSRRADDDRFPRRGDDSRPGPWRPLVKPGGWREKEKAREESWGPPRESRPSEE
REWDREKERDRDNQDREENDKDPERERDRERDVDREDRFRRPRDEGGWRRGPAEESSSWR
DSSRRDDRDRDDRRRERDDRRDLRERRDLRDDRDRRGPPLRSEREEVSSWRRADDRKDDR
VEERDPPRRVPPPALSRDRERDRDREREGEKEKASWRAEKDRESLRRTKNETDEDGWTTV
RR
Function
RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. 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 ; (Microbial infection) Essential for the initiation of translation on type-1 viral ribosomal entry sites (IRESs), like for HCV, PV, EV71 or BEV translation ; (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

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Definitive Altered Expression [1]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive DIS3KLUX Definitive Altered Expression [1]
Lung adenocarcinoma DISD51WR Definitive Biomarker [2]
Prostate cancer DISF190Y Definitive Biomarker [3]
Adenocarcinoma DIS3IHTY Strong Biomarker [4]
Adult glioblastoma DISVP4LU Strong Altered Expression [5]
Amyloidosis DISHTAI2 Strong Biomarker [6]
Astrocytoma DISL3V18 Strong Altered Expression [5]
Bone osteosarcoma DIST1004 Strong Biomarker [7]
Brain neoplasm DISY3EKS Strong Altered Expression [8]
Breast neoplasm DISNGJLM Strong Altered Expression [9]
Carcinoma DISH9F1N Strong Altered Expression [10]
Chronic hepatitis B virus infection DISHL4NT Strong Altered Expression [11]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [12]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [13]
Glioblastoma multiforme DISK8246 Strong Altered Expression [5]
Glioma DIS5RPEH Strong Altered Expression [14]
Hepatitis B virus infection DISLQ2XY Strong Altered Expression [11]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [15]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [16]
leukaemia DISS7D1V Strong Biomarker [17]
Leukemia DISNAKFL Strong Biomarker [17]
Lung cancer DISCM4YA Strong Biomarker [18]
Lung carcinoma DISTR26C Strong Biomarker [18]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [9]
Myopathy DISOWG27 Strong Biomarker [19]
Nasopharyngeal carcinoma DISAOTQ0 Strong Biomarker [20]
Osteosarcoma DISLQ7E2 Strong Biomarker [7]
Ovarian cancer DISZJHAP Strong Biomarker [21]
Ovarian neoplasm DISEAFTY Strong Biomarker [21]
Prostate carcinoma DISMJPLE Strong Biomarker [3]
Prostate neoplasm DISHDKGQ Strong Biomarker [22]
Pulmonary fibrosis DISQKVLA Strong Biomarker [23]
Renal fibrosis DISMHI3I Strong Biomarker [24]
Squamous cell carcinoma DISQVIFL Strong Biomarker [25]
Stomach cancer DISKIJSX Strong Biomarker [26]
Autism DISV4V1Z moderate Biomarker [27]
Bladder cancer DISUHNM0 moderate Altered Expression [28]
Cervical carcinoma DIST4S00 moderate Genetic Variation [29]
Head-neck squamous cell carcinoma DISF7P24 moderate Biomarker [30]
Intellectual disability DISMBNXP moderate Biomarker [27]
Neurodevelopmental disorder DIS372XH moderate Biomarker [27]
Urinary bladder cancer DISDV4T7 moderate Altered Expression [28]
Acute lymphocytic leukaemia DISPX75S Disputed Biomarker [31]
Invasive ductal breast carcinoma DIS43J58 Limited Biomarker [32]
Non-small-cell lung cancer DIS5Y6R9 Limited Biomarker [33]
Parkinson disease DISQVHKL Limited Altered Expression [34]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Etoposide DMNH3PG Approved Eukaryotic translation initiation factor 3 subunit A (EIF3A) increases the response to substance of Etoposide. [54]
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19 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [35]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [36]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [37]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [38]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [39]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [40]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [41]
Quercetin DM3NC4M Approved Quercetin affects the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [42]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [43]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [44]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [45]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [44]
Vitamin C DMXJ7O8 Approved Vitamin C decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [46]
Tamibarotene DM3G74J Phase 3 Tamibarotene decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [36]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [47]
PMID28870136-Compound-48 DMPIM9L Patented PMID28870136-Compound-48 increases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [50]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [51]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [52]
Phencyclidine DMQBEYX Investigative Phencyclidine decreases the expression of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [53]
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⏷ Show the Full List of 19 Drug(s)
2 Drug(s) Affected the Biochemical Pathways of This DOT
Drug Name Drug ID Highest Status Interaction REF
DNCB DMDTVYC Phase 2 DNCB increases the metabolism of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [48]
cinnamaldehyde DMZDUXG Investigative cinnamaldehyde increases the metabolism of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [48]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [49]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Eukaryotic translation initiation factor 3 subunit A (EIF3A). [49]
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References

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10 Carcinoma-associated eIF3i overexpression facilitates mTOR-dependent growth transformation.Mol Carcinog. 2006 Dec;45(12):957-67. doi: 10.1002/mc.20269.
11 New liver cancer biomarkers: PI3K/AKT/mTOR pathway members and eukaryotic translation initiation factors.Eur J Cancer. 2017 Sep;83:56-70. doi: 10.1016/j.ejca.2017.06.003. Epub 2017 Jul 14.
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19 Deficiency of a 180-kDa extracellular matrix protein in Fukuyama type congenital muscular dystrophy skeletal muscle.Neuromuscul Disord. 2002 Feb;12(2):117-20. doi: 10.1016/s0960-8966(01)00251-6.
20 Overexpression of asparagine synthetase and matrix metalloproteinase 19 confers cisplatin sensitivity in nasopharyngeal carcinoma cells.Mol Cancer Ther. 2013 Oct;12(10):2157-66. doi: 10.1158/1535-7163.MCT-12-1190. Epub 2013 Aug 16.
21 eIF3a improve cisplatin sensitivity in ovarian cancer by regulating XPC and p27Kip1 translation.Oncotarget. 2015 Sep 22;6(28):25441-51. doi: 10.18632/oncotarget.4555.
22 Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
23 Inhibitory effect of l-mimosine on bleomycin-induced pulmonary fibrosis in rats: Role of eIF3a and p27.Int Immunopharmacol. 2015 Jul;27(1):53-64. doi: 10.1016/j.intimp.2015.04.048. Epub 2015 May 5.
24 Knockdown of elF3a inhibits collagen synthesis in renal fibroblasts via Inhibition of transforming growth factor-1/Smad signaling pathway.Int J Clin Exp Pathol. 2015 Aug 1;8(8):8983-9. eCollection 2015.
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27 Collybistin binds and inhibits mTORC1 signaling: a potential novel mechanism contributing to intellectual disability and autism.Eur J Hum Genet. 2016 Jan;24(1):59-65. doi: 10.1038/ejhg.2015.69. Epub 2015 Apr 22.
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29 The eIF3a Arg803Lys genetic polymorphism is associated with susceptibility to and chemoradiotherapy efficacy in cervical carcinoma.Kaohsiung J Med Sci. 2017 Apr;33(4):187-194. doi: 10.1016/j.kjms.2017.01.008. Epub 2017 Mar 13.
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34 Altered machinery of protein synthesis is region- and stage-dependent and is associated with -synuclein oligomers in Parkinson's disease.Acta Neuropathol Commun. 2015 Dec 1;3:76. doi: 10.1186/s40478-015-0257-4.
35 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
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