8 exons, 7 introns (1^st intron within 5UTR), plus a rare optional exon within first intron as found in several ESTs (e.g. emb-CR981691.1, dbj-DC388133.1, dbj-DC406334.1).
Presumably a second promoter, about 800 nt upstream of the most common transcription start, provides an alternative first exon about 320 nt long, as deduced from some ESTs at NCBI (e.g. dbj-DC316623.1, gb-BU173251.1, dbj-DC358918.1).
Introns number 2, 3, 4, 6 are phase 0 (between codons), introns number 5, 7 are phase 1 (between 1^st and 2^nd base of codon).
A validated C-G non-synonimous polymorphism has been reported at 1^st position of codon 382 (Arg-Gly), plus a few single-hit non-synonimous and some synonymous within CDS. Several others within 3UTR and introns (SNP source).

The main processed mRNA encompasses exons 1, 2, 3, 4, 5, 6, 7, 8, this last can be in short or long form. In a few cases also exon 1 is retained. In a few cases exons 1 (and 1) are substituted by the alternative exon from a putative upstream minor promoter, as described above. Moreover, a quite high number of processed transcripts that, after exons 1 and 2, retain intron 2, which introduces a stop codon 22 residues downstream of exon 2 are found (see for instance some of the many ESTs: dbj-DC389722.1, dbj-DC341899.1, dbj-DC414491.1).

About 20 complete or approximately complete intronless pseudogenes, likely generated by retrotransposition, a few of them exempt from frameshifs and with only a few missenses, are present throughout the genome. Two of them harbour a few hundreds nt long insert each, not related to introns of the expressed gene.
All of them show a higher homology to EEF1A1 than to EEF1A2. Most of the pseudogenes find an orthologous counterpart within the chimpanzee genome.
EEF1AL3 (9q34) (highly homologous); EEF1AL4 (7p15.3) (highly homologous but with 1 frameshift); EEF1AL5-LOC390924 (19q13.12) (contains a 502 nt insert); EEF1AL6 (3q27.1); EEF1AL7 (4q24); EEF1AL8-LOC100132804 (7q35); EEF1AL9 (1p21.3); EEF1AL10-LOC644604 (2q12); EEF1AL11 (5p15.1) (rather highly homologous); EEF1AL12-LOC647167 (1q31.3); EEF1AL13-LOC100130211 (Xq21.2) (lacking about 300 initial codifying nt); LOC124199 (16p12.1) (contains a 307 nt insert); LOC387845 (12p12.3); LOC389223 (4q28.3); LOC401717 (12q12); LOC442709 (7q21.13) (harbours a 21 nt deletion); LOC645693 (15q21.2); LOC645715 (3p22.1); LOC646612 (3q22.3) (lacking about 120 initial codifying nt); LOC728672 (12p12.3); LOC100128082 (5p12).

The major form of the protein is 462 residues long, composed by three domains, as shown by the diagram, that relates also the protein domains (lower bar) with mRNA coding exons (upper bar).

462 residues, theoretical MW: 50140.8 Da, theoretical isoelectric point: 9.7. eEF1A1 is one of the alpha subunit forms of the elongation factor 1 complex, that interacts with aminoacylated tRNA and delivers it to the A site of the ribosome during the elongation phase of protein synthesis. The other form is eEF1A2, encoded by a different gene, EEF1A2, located in chromosome 20.

EEF1A1 is constitutively expressed in all tissues, with the exception of adult brain, heart and skeletal muscle, where EEF1A2 expression is found.

Mostly cytoplasmic, but also nuclear.

Canonical function: aa-tRNA delivery to ribosome in mRNA translation
The eukaryotic elongation factor 1A (eEF1A1, formerly EF-1alpha or eEF1A) protein belongs to the G-protein superfamily, is one of most abundantly expressed protein in mammalian cells and participates to mRNA translation. It carries aminoacyl-tRNA (aa-tRNA) to the A site of the ribosome as a ternary complex eEF1A1-GTP-aa-tRNA. In mammalian, it is ubiquitously expressed with exception of skeletal muscle, heart and brain where during terminal differentiation eEF1A2 is produced (Knudsen et al., 1993).
Moonlighting functions: cytoskeletal remodelling, protein folding and degradation, cell signalling modulation, control of cell growth, apoptosis and cell cycle
1) eEF1A1 and cytoskeletal remodelling. The most relevant non canonical function of eEF1A1 is the modulation of cytoskeleton organization. eEF1A has activity on microtubule severing and bundling. It has a specific site to bind actin that is different from that for the binding of aa-tRNA (Gross and Kinzy, 2005). eEF1A binding to F-actin is modulated by Rho/Rho-kinase pathway. Phosphorylation by Rho kinase decreases the binding of eEF1A1 to F-actin and F-actin bundling. Myosin phosphatase acts in antagonist fashion on eEF1A1 to modulate actin cytoskeletal organization (Izawa et al., 2000).
2) eEF1A1 and protein degradation and folding. eEF1A controls translational fidelity by binding to incorrectly folded proteins but not to correctly folded ones. The incorrectly folded proteins are then directed to degradation pathway (Hotokezaka et al., 2002). eEF1A plays a role in recognition and degradation of co-translationally damaged and ubiquitylated proteins promoting their translocation to proteasome through interaction with proteasome subunit Rpt1 (Chuang and Madura, 2005). eEF1A exhibits chaperone-like activity by promoting renaturation of enzymes such as aminoacyl-tRNA synthetases, likely contributing to maintain the efficiency of translational machinery (Lukash et al., 2004).
eEF1A1 takes part in the aggregosome formation upon proteosome failure by activating heat shock response to degrade uncorrected folded proteins, to favor clearance of protein aggregates and to protect cell from proteotoxicity by favoring autophagy (Meriin et al., 2012).
3) eEF1A1 and control of cell cycle, growth and death. eEF1A as ribonucleoprotein complex, containing a non-coding RNA, binds to and mediates activation of heat-shock transcription factor 1 (HSF1) to protect the cell from heat-shock (Shamovsky et al., 2006). Induction of the non-constitutive eEF1A1 expression in cardiomyocytes as response to lipotoxic ER-stress promotes cell death likely by activation of eEF1A1-dependent cytoskeletal modifications triggering apoptosis (Borradaile et al., 2006). eEF1A1 interacts with the HDM2 gene product at a binding site for eEF1A1 overlaps with that for p53. In normal cells eEF1A1 could promote cell apoptosis by preventing p53 sequestration by HDM2 (Frum et al., 2007). Likely both eEF1A1 and eEF1A2 interacts with the zinc finger protein ZPR1 in response to mitogenic stimuli, redistributing eEF1A1/2 and ZPR1 in the nucleus. This interaction is essential for normal cell proliferation and growth. Thus the interaction eEF1A1/2-ZPR1 is required for normal cell cycle progression (Mishra et al., 2007). eEF1A1 is an interactor of Bood POZ containing gene type 2 (BPOZ-2) that promotes eEF1A1 ubiquitylation and degradation via 26S proteasome. BPOZ-2 inhibits GTP binding to eEF1A1 thus preventing translation. BOPZ-2 is transcriptionally activated by phosphate and tensin homologue deleted on chromosome 10 (PTEN). It has been suggested that PTEN exerts growth inhibition effects in cells not only by antagonizing PI3K-Akt signalling pathway, but also inducing BPOZ-2 expression to degrade eEF1A1. In this manner, in normal cells, the transition from growing to resting phases is mediated by BPOZ-2/eEF1A1 interaction, thus leading to prevention of translation and induction of eEF1A1 degradation by 26S proteasome pathway (Koiwai et al., 2008). eEF1A1 is implicated in a novel cell cycle check-point to prevent tetraploidy in binucleated cells. In tetraploids, cell death, preventing aneuploidy malignancies, is mainly controlled in a caspase-independent manner by the down-regulation of eEF1A1 levels. eEF1A1 mRNA accumulates in specialized P bodies to reduce the expression of the proteins. The prominent signal in the eEF1A1 mRNA for its translational repression and degradation is in the 5-UTR. Exogenous expression of eEF1A1 inhibits cell death in tetraploids. Notably, exogenous expression of eEF1A2 whose mRNA 5-UTR differs from that of eEF1A1 inhibits cell death in tetraploids, thus suggesting another mechanism by which eEF1A2 could promote tumour development (Kobayashi and Yonehara, 2009).
Cell adhesion to the extracellular matrix is an essential biological event for cell survival and proliferation in multicellular organisms. Disruption of integrin-mediated cell adhesion leads to a specific type of apoptosis known as anoikis in most non-transformed cells. Recent evidences show eEF1A to act as a membrane receptor for the cryptic anti-adhesive site of fibronectin, which contributes to cell regulation, including anoikis, through negative modulation of cell anchorage. Possibly, the membrane-resident eEF1A may interact with beta1-integrins inactivating their functions in cell adhesion (Itagaki et al., 2012).
Down-regulation of eEF1A1 seems to be specific to senescence. Changes in eEF1A expression levels has been proposed also as promising marker for the detection of cellular cancer senescence induced by a variety of treatments, such as ionizing radiation (Byun et al., 2009).
4) eEF1A1 and cell signalling modulation. Besides eEF1A2, in adult mouse neurons eEF1A1 is expressed too and it is able to regulate the recycle of M4 muscarinic acetylcholine receptors (mAChR). Thus, eEF1A1 plays a role in locomotor activity of neurons (McClatchy et al., 2006). eEF1A1 modulates the activities of sphingosine kinases (SK1 and SK2). Phosphorylated and non-phosphorylated eEF1A1 forms interact with phosphorylated and non phosphorylated SK1 and SK2 and this results in an increased enzymatic activity of both SK1 and SK2. In this respect, overexpression of eEF1A1 in quiescent cells has been suggested to play a role in oncogenesis by increasing SK1 and SK2 activities (Leclercq et al., 2008). eEF1A1 is involved in the regulation of vascular function mediated by TNF-alpha. eEF1A1 binds to 3-UTR of the endothelial nitric oxide synthase (eNOS) to regulate post-translational eNOS mRNA stability. In the human endothelial cell line HUVEC, TNF-alpha-mediated eNOS mRNA destabilization involves eEF1A1 to reduce eNOS mRNA levels (Yan et al., 2008).
The different phosphorylation pattern between eEF1A1 and eEF1A2 especially at tyrosine levels has been suggested to determine structural differences of the two isoforms. In particular, eEF1A1 behaves a more extended structure with respect to the more compact one of eEF1A2 (Negrutskii et al., 2012).
Phosphorylation of eEF1A1 on serine (S21) and threonine (T88) residues by Raf kinases regulates eEF1A1 stability. The in vitro phosphorylation of S21 residue in both eEF1A1 and eEF1A2 proteins by Raf kinases is suggested to cause conformational change in the proteins thus impairing GDP/GTP exchange factor interaction and switching the proteins from the protein biosynthesis to the non-canonical functions. Although S21 phosphorylation has not been found in vivo, in eEF1A constructs transfected COS 7 cells, S21 and T88 mutants showed that these sites affect proteins stability. Interestingly, eEF1A1 has a unique phosphorylation site on threonine and tyrosine (T88 and Y86, respectively). Furthermore, phosphorylation deficiency at S21 decreased protein half-time and increased cell apoptosis. Thus modulation of eEF1A1 phosphorylation at S21 is proposed to be implicated in cell proliferation and apoptosis regulation (Sanges et al., 2012).
eEF1A1 is involved also in cytokine cell signaling. In particular, TGFβ1 signalling regulates cell proliferation by acting on TβR-I that phosphorylates eEF1A1 at the Ser300 located in the domain for aa-tRNA binding. This impairs protein synthesis and leads to a lower proliferation rate of the cells. Worth of note that this effect is exerted directly on mRNA translation without transcriptional activation (Lin and Souchelnytskyi, 2011).
eEF1A1 is also a component of the ribonucleoprotein complex in the transcript-selective translational regulatory pathway mediated by the TGFβ-activated translational element (BAT). BAT is a 33-nt structural RNA element in the 3-UTR of disabled-2 (Dab2) and interleukin like EMT inducer (ILEI). Dab2 and ILEI are two mRNAs mediating epithelial to mesenchymal transition. TGFβ-induced EMT is essential during embryonic development. In BAT element, eEF1A1 interacts with hnRNP E1 to inhibit translation, blocking the progression of the 80S ribosome by preventing eEF1A1 release from A site following hydrolysis of GTP. In this way the translation is inhibited by the stall at the eEF1A1-dependent elongation stage. Thus eEF1A1 and hnRNP E1 play a fundamental role in EMT by repressing specific gene expression (Hussey et al., 2011).
In U343 glioma cells eEF1A1 was found to be the target of heteroalkylketones, compounds that lower interleukin-6 (IL-6) activity in chronic inflammation. By this finding, eEF1A1 was shown to play a critical role in chronic inflammation sustaining IL-6 activity by forming a complex with STAT3 and PKCδ that promotes phosphorylation of STAT3 at serine 727. This in turn triggers NF-kB/STAT3 interaction enhancing IL-6 expression (Schulz et al., 2014).
In neurons, both eEF1A1 and eEF1A2 isoforms have been found to bind to gephyrin protein, a scaffold protein which is thought to anchor GABAA-receptors to the cytoskeleton. Overexpression of both eEF1A proteins in cultured hippocampal neurons has been also associated with a significant increase in number, size and density of postsynaptic gephyrin clusters. Therefore, eEF1A proteins involvement in modulating receptor cluster formation and/or maintenance in neurons and in the morphology of postsynaptic membrane specializations at inhibitory synapses, is strongly emphasize (Becker et al., 2013).

Highly homologous over the entire length to:
- EEF1A2 (92% identities).
Moderately homologous over all three domains, higher for the first one, to:
- HBS1L, a member of the GTP-binding protein family expressed in erythroid progenitor cells (39% identities),
- GSPT1, a GTP-binding protein involved in G1 to S phase transition (38% identities),
- GSPT2, a GTP-binding protein involved in G1 to S phase transition (37% identities),
- TUFM, Tu translation elongation factor, mitochondrial (31% identities).