EEF1E1 (eukaryotic translation elongation factor 1 epsilon 1) was identified for the first time by Mao and colleagues in 1998 (Mao et al, 1998). EEF1E1 is a protein-coding gene that starts at 8,079,395 nt and ends at 8,102,595 nt from pter. It has a length of 23,201 bp, counts 5 exons, and the current reference sequence is NC_000006.12. It is proximal to BLOC1S5 (biogenesis of lysosomal organelles complex 1 subunit 5, alias MUTED) gene. Read-through transcription exists between BLOC1S5 gene and EEF1E1 gene with forming the read-through transcript EEF1E1-BLOC1S5 (alias EEF1E1-MUTED) that is a candidate for nonsense-mediated mRNA decay (NMD) and it is unlikely to produce a protein product (He et al, 2018).
Near to the genomic sequence of EEF1E1 there is a strong promoter transcriptional element that is located at +1.0 kb. Enhancer transcriptional elements are located at +22.0 Kb and at +18.1 Kb respectively.

Alternative splicing for EEF1E1 brings to multiple transcript variants. In addition, a read-through transcription is known between EEF1E1 and the neighboring downstream MUTED (muted homolog) gene. Two main alternative splicing transcript variants for EEF1E1 were detected although several others were reported. In addition, it was speculated the presence of six protein isoforms, but only two are properly described, i.e. the isoform 1 of 174 residues and the isoform 2 that counts 139 residues.
The main characteristics of the alternative splicing transcript variants are reported in Table.1.
The transcript variant 1 mRNA has reference sequence NM_004280.5 and it is 1047 bp long. The 5UTR counts 27 nt, the CDS is extended from 28 to 552 nt, while the 3UTR covers the last 495 nt.
The transcript variant 2 mRNA has reference sequence NM_001135650.2 and it is 562 bp long. The 5UTR counts 27 nt, the CDS is extended from 28 to 447 nt, while the 3UTR covers the last 115 nt.

Name	Variant	RefSeq (1)	Transcript ID	Exons	Type	Lenght (bp)	Isoform	Alias	RefSeq (2)	Lenght (aa)	MW (kDa)	pI
EEF1E1-001	-	-	ENST00000488226.2	2	protein coding	443	-	-	-	94	(?)	(?)
EEF1E1-002	Var.1	NM_004280.5	ENST00000379715.5	4	protein coding	1077	isoform 1	O43324-1	NP_004271.1	174	19.81	8.55
EEF1E1-003	-	-	ENST00000507463.1	3	protein coding	654	-	-	-	150	16.69	(?)
EEF1E1-004	Var.2	NM_001135650.2	ENST00000429723.2	4	protein coding	562	isoform 2	O43324-2	NP_001129122.1	139	15.55	7.95
EEF1E1-005	-	-	ENST00000502429.1	4	protein coding	591	-	-	-	136	(?)	(?)
EEF1E1-006	-	-	ENST00000515633.1	3	protein coding	460	-	-	-	56	5.89	(?)

Table.1 Alterative splicing variants and isoforms of EEF1E1. (reworked from http://grch37.ensembl.org; https://www.ncbi.nlm.nih.gov; https://web.expasy.org/protparam/; https://www.uniprot.org). ncRNA = non-coding RNA; nonsense md = nonsense mediated decay; (?) = undetermined; MW = molecular weight; pI = theoretical pI.

According to Entrez Gene, the analysis of the human genome revealed the presence of an EEF1E1-related pseudogene on chromosome 2. This pseudogene was appointed as eukaryotic translation elongation factor 1 epsilon 1 pseudogene 1, alias EEF1E1P1 and it is classified as a processed pseudogene (http://www.ensembl.org/index.html). Its gene ID is 100130388, its reference is NC_000002.12, and its location is 2q13. EEF1E1P1 starts at 111,887,890 nt and ends at 111,889,485 nt with a length of 1,596 nt. It virtually encodes a non-coding transcript of 430 bp named EEF1E1P1-201 (Ensembl Ref: ENST00000446998.2). The real presence of this transcript and its possible role in the cell are totally unknown.
If EEF1E1P1 has any regulatory role in the expression of the respective gene as described for others (Hirotsune et al., 2003), is only speculation in the absence of experimental evidence. Currently, there is no evidence about the involvement of this pseudogene in human cancers or in other diseases.

The eukaryotic translation elongation factor 1 epsilon 1 (alias eEF1E1, p18, AIMP3) is the smallest component of the Multiaminoacyl-tRNA Synthetase complex (alias MARS). The exact position of EEF1E1 in the MARS complex is still unknown. However, it seems to be localized on the surface of the MARS complex and it seems to interact with the eEF1H complex (Deineko V.V., 2008).
EEF1E1 is a small globular protein with a length of 174 amino acids and a molecular weight of 19,8 kDa.
eEF1E1 shows strong sequence similarity with eukaryotic translation elongation factor 1 beta 2 ( EEF1B2) and eukaryotic translation elongation factor 1 gamma ( EEF1G) (Quevillon and Mirande, 1996) and with the N-terminal sequence of valyl-tRNA synthetase (Deineko V.V., 2008).
eEF1E1 shows many domains in both isoforms: the amino half terminal is unique for both isoforms and shows an N-terminal-like domain not well characterized followed by a linker domain, while the major differences between the two isoforms are in the carboxyl half terminal. In fact, in the carboxyl half terminal of isoform 1 there are reported two domain overlapping, i.e. a Glutathione S-transferase C-terminal-like domain (GST_C_AIMP3), folded in alpha-helical, and a more general and not well characterized C-terminal domain. In isoform 2, there is a unique region called C-terminal domain of the Glutathione S-transferase family (GST_C_family). The fold of this domain is alpha-helical (see figure.2).
EEF1E1 interacts with other members of the MARS complex and one interactional model was proposed (Mirande, 2017) although its exact interactions need to be still clarified.
Post-translational modifications. Some post-translational modifications are observed, such as phosphorylation and acetylation (https://www.ncbi.nlm.nih.gov).

eEF1E1 is expressed widely in human tissues and normal cells (https://www.genecards.org; https://www.proteinatlas.org/ENSG00000124802-EEF1E1/tissue) while its expression is altered in many cancer types. Frequently it is downregulated in various cancer tissues (Park et al, 2005).
Cells that show overexpression of eEF1E1 show an acceleration of senescence and also defects in nuclear morphology (Oh et al, 2010).

EEF1E1 is located mostly in the cytoplasm but it was also found in the nucleus.

It is well known that in eukaryotic cells the various components of translation machinery are properly organized into two main multienzyme structures: eEF1H (macromolecular eukaryotic translation elongation factor-1 complex), formed by the translation elongation factors (EEF1B2, EEF1D, EEF1G) and VARS (valyl-tRNA synthetase), and MARS (Multiaminoacyl-tRNA Synthetase complex or multi-tRNA synthetase complex, alias MSC), formed by nine aminoacyl-tRNA synthetases (AARSs) specific for amino acids Glu, Pro (EPRS1 (glutaminylprolyl-tRNA synthetase)), Ile (IARS1), Leu (LARS1), Met (MARS1, methionyl-tRNAsynthetase), Gln (QARS1), Lys (KARS1), Arg (RARS1), and Asp (DARS1) and other auxiliary non-synthetase protein components, called also aminoacyl-tRNA synthetase (ARS)-interacting multifunctional proteins (AIMPs), i.e AIMP1 (p43), AIMP2 (p38) and eEF1E1 (AIMP3, alias p18)( Cho et al, 2015; Shalak et al, 2007; Quevillon and Mirande, 1996).
It is well known that in eukaryotic cells the various components of translation machinery Therefore, the main canonical function of eEF1E1 is to play a role as an auxiliary component of the macromolecular aminoacyl-tRNA synthetases complex in the elongation step of translation, in particular, it interacts with several aminoacyl-tRNA synthetases (Tao et al, 2017) and it could contribute to the anchorage of MARS complex to EF1H complex (Quevillon and Mirande, 1996).
Other functions (non-canonical roles): in addition to what has already been said, it seems to play a role in embryonic development of the mammalian face and other structures (Fowles et al, 2003).
eEF1E1 has the ability to translocate into the nucleus in response to DNA damage where it has a role in the DNA damage response in association with serine/threonine kinases ATM / ATR and TP53. In fact, it was found a positive relationship between expression levels of eEF1E1 and TP53, i.e. high expression levels of eEF1E1 are correlated with elevated TP53 levels, while eEF1E1 depletion leads to the block of TP53 induction (Park et al, 2005). The eEF1E1 loss-of-function phenotype leads to various kinds of abnormalities: in particular, one allele inactivation increases the susceptibility to spontaneous tumors while the inactivation of both EEF1E1 alleles caused embryonic lethality (Park et al, 2005). The importance of eEF1E1 in embryogenesis is previously reported (Fowles et al, 2003) while in the context of the tumors, eEF1E1 could be a haploinsufficient tumor suppressor (Park et al, 2005) that can accelerate cellular senescence (Kang et al, 2012).
eEF1E1 in involved in the degradation of mature Lamin A ( LMNA) which is a major component of the nuclear envelope matrix (Tao et al, 2017).

eEF1E1 is highly conserved and its homology between the species is reported in Table.2

Organism	Species	Symbol	DNA Identity (%)	PROT Identity (%)
Human	H.sapiens	EEF1E1	100	100
Chimpanzee	P.troglodytes	EEF1E1	99.2	100
Macaco	M.mulatta	EEF1E1	97.5	99.4
Wolf	C.lupus	EEF1E1	92.5	96.0
Cattle	B.taurus	EEF1E1	89.8	96.5
Mouse	M.musculus	Eef1e1	86.6	88.5
Rat	R.norvegicus	Eef1e1	83.7	87.9
Chicken	G.gallus	EEF1E1	75.9	77.6
Xenopus tropicalis	X.tropicalis	Eef1e1	67.6	69.6
Zebrafish	D.rerio	Eef1e1	63.0	63.7

Table.2 EEF1E1 homology (reworked from ps://www.ncbi.nlm.nih.gov/homologene)

A great number of mutations in the genomic sequence and in the amino acid sequence for EEF1E1 were discovered in cancer cells that are obviously genetically more unstable respect normal ones. However, depletion of EEF1E1 causes itself genomic instability in cells (Kim et al, 2018) and makes the cells susceptible to transformation by single oncogenes (Park et al, 2006).
The genomic alterations observed include also the formation of novel fusion genes. However, there are no sufficient experimental data yet to understand the repercussions on cellular behavior and so the implications in cancer of these alterations.