EIF3A (eukaryotic translation initiation factor 3, subunit A)

2010-11-01   Ji-Ye Yin , Zizheng Dong , Jian-Ting Zhang 

Department of Pharmacology, Toxicology, IU Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA





The eIF3a gene spans over a region of 46 kbp DNA including 22 coding exons and 2 non-coding exons (exon 2 and exon 10).


The eIF3a mRNA consists of about 5256 nucleotides with an open reading frame (ORF) of 4149 bases.


No pseudogene has been identified.


Atlas Image
Schematic presentation of eIF3a domain structure. Human eIF3a consists of 1382 amino acid residues with three putative domains of PCI, spectrin, and 10-amino acid repeat.


Structure: The eIF3a protein consists of 1382 amino acid residues with an apparent molecular weight of ~170 kDa as determined using SDS-PAGE (Pincheira et al., 2001b). Its primary sequence contains a PCI (Proteasome, COP9, Initiation factor 3) domain, a spectrin domain, and a 10-amino acid repeat domain (Pincheira et al., 2001b). It has phosphorylation sites at Ser-881, Ser-1198, Ser-1336 and Ser-1364 (Damoc et al., 2007). The PCI domain spans from amino acid 405 to 495, which contains purely alpha-helix (Pincheira et al., 2001b). Since most of the proteins containing this domain are part of a multi-protein complex, it is tempting to speculate that this domain may be involved in the interaction of eIF3a with other molecules in eIF3 (Hofmann and Bucher, 1998). The spectrin domain, which consists of 112 amino acids, is a sequence almost identical to spectrin, an actin-binding protein (Pascual et al., 1997). Although the exact function of this domain remains unknown, it may be responsible for the binding of eIF3a to actin filaments (Pincheira et al., 2001a). The 10-amino acid repeat domain spanning 925-1172 amino acids is the largest domain of eIF3a. It can be divided into about 25 repeats of DDDRGPRRGA (Johnson et al., 1997; Pincheira et al., 2001b). This domain has been suggested to contribute to interaction of eIF4B and eIF3a (Methot et al., 1996).
Regulatory role in gene expression: eIF3a not only functions as a regular translation initiation factor and participates in translation initiation of global mRNAs, it also regulates the translation of a subset of mRNAs which are involved in cell cycle, tumorigenesis and DNA repair (Yin et al., 2010). It has been observed that overexpression of ectopic eIF3a increases the expression of ribonucleotide reductase M2 (RRM2) and alpha-tubulin, but decreases that of p27kip without affect their mRNA levels (Dong and Zhang, 2003; Dong et al., 2004). Recently, it has also been found that eIF3a suppresses the synthesis of DNA repair proteins including: XPA, XPC, RPA 14, RPA 32 and RPA 70 KDa (Yin et al., unpublished data). Although the detailed mechanism of eIF3a regulation in translational control is yet to be determined, it is thought that eIF3a may regulate these genes at their 5- and 3-UTRs (Dong and Zhang, 2003; Dong et al., 2004).
Binding with other molecule: Since eIF3a is the largest subunit of the eIF3 complex, the interaction between eIF3a and other subunits of eIF3 were intensively studied. It can bind with eIF3b (Methot et al., 1997), eIF3c (Valasek et al., 2002), eIF3f (Asano et al., 1997), eIF3h (Asano et al., 1997), eIF3j (Valasek et al., 1999) and eIF3k (Mayeur et al., 2003). During the translation initiation, the amino terminal domain of eIF3a can bind with 40S protein RPS0A, while the C terminal domain binds with the 18S rRNA (Valasek et al., 2003). Apart from above molecule, eIF3a has also been shown to interact with eIF4B (Methot et al., 1996), actin (Pincheira et al., 2001a), and cytokeratin 7 (Lin et al., 2001).


eIF3a is ubiquitously expressed in all human tissues (Nagase et al., 1995; Scholler and Kanner, 1997; Pincheira et al., 2001b). However, its expression is higher in proliferating tissues such as bone marrow, thymus and fetal tissues (Pincheira et al., 2001b).


eIF3a has been found in both cytoplasmic and membrane fractions and the cytoplasmic eIF3a appears to be phosphorylated at its serine residues (Pincheira et al., 2001a). However, 70-80% of eIF3a is cytoplasmic.


eIF3a has been shown to play important roles in the biological processes: translational initiation (including generation of ribosomal subunit from 80S ribosomes, 43S pre-initiation complex formation and 48S pre-initiation complex formation) (Dong and Zhang, 2006), regulation of mRNA translation (Dong and Zhang, 2003; Dong et al., 2004), differentiation and development (Liu et al., 2007), apoptosis (Nakai et al., 2005), cell cycle regulation (Dong et al., 2009), oncogenesis (Dong and Zhang, 2006; Zhang et al., 2007), and drug response (unpublished observations).


Centrosomin A and B have strong homology to eIF3a. The spectrin domain is essentially identical to spectrin.



Two SNPs (rs10787899 and rs3824830) were found to be associated with higher risk of breast cancers (Olson et al., 2009).

Implicated in

Entity name
Breast cancer
eIF3a was overexpressed in breast cancer tissues.
The eIF3a was highly expressed in all tested tissues from breast cancer patients compared with normal control tissues, which indicated that it may contribute to the oncogenesis of breast cancer (Bachmann et al., 1997).
Entity name
Cervical carcinoma
eIF3a was found to be a molecular parameter of predicting cervical carcinoma progression and prognoses.
Patients with high eIF3a expression have better prognosis than those with lower ones, thus it will be useful in predicting cervical cancer prognosis (Dellas et al., 1998).
Entity name
Gastric carcinoma
eIF3a is an early tumor maker of gastric carcinoma.
eIF3a was highly expressed in well differentiated, early invasive stage and no-metastases gastric carcinoma (Chen and Burger, 2004).
Entity name
Lung cancer
eIF3a is highly expressed in lung cancer compared with normal tissues.
eIF3a expression in human lung cancers negatively correlates with patient response to platinum-based chemotherapy, suggesting that lung cancer patients with higher eIF3a expression level respond better to platinum-based chemotherapy (Yin et al., unpublished findings).
eIF3a was over-expressed in all types of human lung cancer. Furthermore, it is ubiquitously highly expressed in proliferating and developing tissues. This suggested eIF3a may be involved in oncogenesis of lung cancer (Pincheira et al., 2001b).
Entity name
Esophagus squamous-cell carcinoma
eIF3a may be a biomaker of esophagus squamous-cell carcinoma.
Patients with higher eIF3a expression have better overall survival and fewer tumor metastases than those with lower ones (Chen and Burger, 1999).


Pubmed IDLast YearTitleAuthors
93411431997Structure of cDNAs encoding human eukaryotic initiation factor 3 subunits. Possible roles in RNA binding and macromolecular assembly.Asano K et al
90412051997Cloning of a novel protein overexpressed in human mammary carcinoma.Bachmann F et al
153820632004p150 overexpression in gastric carcinoma: the association with p53, apoptosis and cell proliferation.Chen G et al
173223082007Structural characterization of the human eukaryotic initiation factor 3 protein complex by mass spectrometry.Damoc E et al
97629391998Expression of p150 in cervical neoplasia and its potential value in predicting survival.Dellas A et al
193273502009Role of eIF3a in regulating cell cycle progression.Dong Z et al
168291252006Initiation factor eIF3 and regulation of mRNA translation, cell growth, and cancer.Dong Z et al
96449721998The PCI domain: a common theme in three multiprotein complexes.Hofmann K et al
90544041997Identification of cDNA clones for the large subunit of eukaryotic translation initiation factor 3. Comparison of homologues from human, Nicotiana tabacum, Caenorhabditis elegans, and Saccharomyces cerevisiae.Johnson KR et al
111697322001Molecular interaction between human tumor marker protein p150, the largest subunit of eIF3, and intermediate filament protein K7.Lin L et al
173815442007Role of eIF3a (eIF3 p170) in intestinal cell differentiation and its association with early development.Liu Z et al
145191252003Characterization of eIF3k: a newly discovered subunit of mammalian translation initiation factor elF3.Mayeur GL et al
89954101997The human homologue of the yeast Prt1 protein is an integral part of the eukaryotic initiation factor 3 complex and interacts with p170.Méthot N et al
88164441996A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3.Méthot N et al
85902801995Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1.Nagase T et al
159790692005Externalization and recognition by macrophages of large subunit of eukaryotic translation initiation factor 3 in apoptotic cells.Nakai Y et al
193778772010Variation in genes required for normal mitosis and risk of breast cancer.Olson JE et al
92979721997Evolution of the spectrin repeat.Pascual J et al
113841032001Identification of a 170-kDa protein over-expressed in lung cancers.Pincheira R et al
91504391997The human p167 gene encodes a unique structural protein that contains centrosomin A homology and associates with a multicomponent complex.Scholler JK et al
104880931999The Saccharomyces cerevisiae HCR1 gene encoding a homologue of the p35 subunit of human translation initiation factor 3 (eIF3) is a high copy suppressor of a temperature-sensitive mutation in the Rpg1p subunit of yeast eIF3.Valásek L et al
126518962003The yeast eIF3 subunits TIF32/a, NIP1/c, and eIF5 make critical connections with the 40S ribosome in vivo.Valásek L et al
124115062002Direct eIF2-eIF3 contact in the multifactor complex is important for translation initiation in vivo.Valásek L et al
209646252011Translational control gone awry: a new mechanism of tumorigenesis and novel targets of cancer treatments.Yin JY et al
171701152007Individual overexpression of five subunits of human translation initiation factor eIF3 promotes malignant transformation of immortal fibroblast cells.Zhang L et al

Other Information

Locus ID:

NCBI: 8661
MIM: 602039
HGNC: 3271
Ensembl: ENSG00000107581


dbSNP: 8661
ClinVar: 8661
TCGA: ENSG00000107581


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
RNA transportKEGGko03013
RNA transportKEGGhsa03013
Metabolism of proteinsREACTOMER-HSA-392499
Eukaryotic Translation InitiationREACTOMER-HSA-72613
Cap-dependent Translation InitiationREACTOMER-HSA-72737
Formation of a pool of free 40S subunitsREACTOMER-HSA-72689
Formation of the ternary complex, and subsequently, the 43S complexREACTOMER-HSA-72695
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43SREACTOMER-HSA-72662
Translation initiation complex formationREACTOMER-HSA-72649
Ribosomal scanning and start codon recognitionREACTOMER-HSA-72702
GTP hydrolysis and joining of the 60S ribosomal subunitREACTOMER-HSA-72706
L13a-mediated translational silencing of Ceruloplasmin expressionREACTOMER-HSA-156827
Gene ExpressionREACTOMER-HSA-74160

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA164713176Platinum compoundsChemicalClinicalAnnotationassociatedPD
PA443622Carcinoma, Non-Small-Cell LungDiseaseClinicalAnnotationassociatedPD
PA444818Lung NeoplasmsDiseaseClinicalAnnotationassociatedPD23127338


Pubmed IDYearTitleCitations
185994412008Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3.112
175816322007Reconstitution reveals the functional core of mammalian eIF3.90
163854512006A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.69
168291252006Initiation factor eIF3 and regulation of mRNA translation, cell growth, and cancer.52
187254002008Poly(A)-binding protein-interacting protein 1 binds to eukaryotic translation initiation factor 3 to stimulate translation.46
216252092011Role of eIF3a in regulating cisplatin sensitivity and in translational control of nucleotide excision repair of nasopharyngeal carcinoma.37
237662932013Two RNA-binding motifs in eIF3 direct HCV IRES-dependent translation.36
249126832014Functional and biochemical characterization of human eukaryotic translation initiation factor 3 in living cells.35
203991882010Structural insights into the COP9 signalosome and its common architecture with the 26S proteasome lid and eIF3.32
236237292013Architecture of human translation initiation factor 3.32


Ji-Ye Yin ; Zizheng Dong ; Jian-Ting Zhang

EIF3A (eukaryotic translation initiation factor 3, subunit A)

Atlas Genet Cytogenet Oncol Haematol. 2010-11-01

Online version: http://atlasgeneticsoncology.org/gene/40425/eif3a