EEF1B2 (eukaryotic translation elongation factor 1 beta 2) was identified for the first time by Sanders and colleagues in 1991 (Sanders et al, 1991) and afterwards, its gene location was described by Pizzuti and colleagues in 1993 (Pizzuti et al, 1993). EEF1B2 is a protein-coding gene that starts at 206,159,594 nt and ends at 206,162,929 nt from pter. It has a length of 3,336 bp and the current reference sequence is NC_000002.12. It is proximal to SNORA41 (small nucleolar RNA, H/ACA box 41) gene, SNORD51 (small nucleolar RNA, C/D box 51) gene and NDUFS1 (NADH:ubiquinone oxidoreductase core subunit S1) gene. Near to the genomic sequence of EEF1B2 there is a strong promoter transcriptional element that is located at -0.2 kb.

Three main alternative splicing transcript variants for EEF1B2 were detected although several others were reported. The three main transcript variants differ from each other only in the 5 UTR. In addition, it was speculated the presence of four protein isoforms, one main isoform of 225 amino acids and other three minor isoforms of 123 residues, 68 residues and 29 residues respectively. However, only the protein with the highest number of amino acids was detected. The main characteristics of the alternative splicing transcript variants are reported in Table.1.
>

Name	Variant	RefSeq (1)	Transcript ID	Exons	Type	Lenght (bp)	Isoform	Alias	RefSeq (2)	Lenght (aa)	MW (kDa)	pI
EEF1B2-201  (EEF1B2-001)	Var.2	NM_021121.3	ENST00000236957.9	7	protein coding	844 (854)	-	P24534	NP_066944.1	225	24.76	4.50
EEF1B2-202  (EEF1B2-201)	Var.3	NM_001037663.1	ENST00000392221.5	7	protein coding	880 (900)	-	P24534	NP_001032752.1	225	24.76	4.50
EEF1B2-203  (EEF1B2-003)	Var.1	NM_001959.4	ENST00000392222.7	6	protein coding	808	-	P24534	NP_001950.1	225	24.76	4.50
EEF1B2-204  (EEF1B2-005)	-	-	ENST00000415904.1	4	nonsense md	649	-	-	-	68	-	-
EEF1B2-205  (EEF1B2-007)	-	-	ENST00000429769.5	8	nonsense md	912	-	-	-	68	-	-
EEF1B2-206 (EEF1B2-009)	-	-	ENST00000435123.1	3	nonsense md	389	-	-	-	29	-	-
EEF1B2-207 (EEF1B2-004)	-	-	ENST00000445505.5	5	protein coding	515	-	-	-	123	-	-
EEF1B2-208 (EEF1B2-010)	-	-	ENST00000455150.1	6	nonsense md	670	-	-	-	68	-	-
EEF1B2-209  (EEF1B2-008)	-	-	ENST00000460760.1	2	retained intron	1025	-	-	-	-	-	-
EEF1B2-210  (EEF1B2-006)	-	-	ENST00000479587.1	3	retained intron	701	-	-	-	-	-	-
EEF1B2-211 (EEF1B2-002)	-	-	ENST00000482103.1	2	retained intron	587	-	-	-	-	-	-

Table.1 Alterative splicing variants and isoforms of EEF1B2.(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
The main mRNA reference sequence is NM_001959.4 and it is 808 bp long. The 5UTR counts 85 nt, the CDS is extended from 86 to 763 nt, while the 3UTR covers the last 45 nt.

According to Entrez Gene, the analysis of the human genome revealed the presence of several pseudogenes for EEF1B2 (Table.2), which are perhaps related to recent retrotransposition events (Chambers et al, 2001). The alternative forms EEF1B3 and EEF1B4 previously designated for EEF1B2 (Pizzuti et al, 1993) have instead proved to be pseudogenes: i.e. EEF1B2P2 and EEF1B2P3 respectively.
If these elements have 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 these pseudogenes in human cancers or in other diseases.

Gene	Gene  name	Gene ID	RefSeq	Locus	Location	Start	End	Lenght (nt)	Main diseases	Reference
EEF1B2P1	EEF1B2 pseudogene 1	1932	NC_000015.10	Chromosome 15	15q21.2	52505029	52505908	880	-	-
EEF1B2P2	EEF1B2 pseudogene 2	1934	NC_000005.10	Chromosome 5	5q13.1	68159175	68159977	803	-	-
EEF1B2P3	EEF1B2 pseudogene 3	644820	NC_000023.11	Chromosome X	Xp22.11	24788347	24789110	764	-	-
EEF1B2P4	EEF1B2 pseudogene 4	100130631	NC_000012.12	Chromosome 12	12q23.3	106901238	106902398	1161	-	-
EEF1B2P5	EEF1B2 pseudogene 5	442227	NC_000006.12	Chromosome 6	6q12	63480050	63481926	1877	-	-
EEF1B2P6	EEF1B2 pseudogene 6	647030	NC_000007.14	Chromosome 7	7q32.3	131661900	131662665	766	-	-
EEF1B2P7	EEF1B2 pseudogene 7	100421756	NC_000002.12	Chromosome 2	2q37.1	232729478	232730276	799	-	-
EEF1B2P8	EEF1B2 pseudogene 8	100421774	NC_000003.12	Chromosome 3	3q26.31	175059315	175060110	796	-	-

Table.2 EEF1B2 pseudogenes (reworked from https://www.ncbi.nlm.nih.gov/gene/1933; https://www.targetvalidation.org; https://www.ncbi.nlm.nih.gov/geoprofiles/)
[ (?) ] uncertain; [ - ] no reference

The eukaryotic translation elongation factor 1 beta 2 (alias eEF1B2, eEF1β, eEF1Bα) is the smallest subunit of the macromolecular eukaryotic translation elongation factor-1 complex (alias eEF1, also called eEF1H)(Cao et al, 2014), a high-molecular-weight form made up of an aggregation of different protein subunits: EEF1A1 (alias eEF1α), EEF1B2, EEF1G (alias eEF1γ, heEF1γ, eEF1Bγ), EEF1D (alias eEF1δ, eEF1Bδ) and VARS2 (valyl t-RNA synthetase val-RS). eEF1H protein complex plays a central role in peptide elongation during eukaryotic protein biosynthesis, in particular for the delivery of aminoacyl-tRNAs to the ribosome mediated by the hydrolysis of GTP. In fact, during the translation elongation step, the inactive GDP-bound form of eEF1A (eEF1A-GDP) is converted to its active GTP-bound form (eEF1A-GTP) by eEF1BGD-complex through GTP hydrolysis. Thus eEF1BGD-complex acts as a guanine nucleotide exchange factor (GEF) for the regeneration of eEF1A-GTP for the next elongation cycle. The physiological role of eEF1B2 in the translation is fundamental to permit the conversion of the inactive form eEF1A-GDP into its corresponding active form eEF1A-GTP. In particular, eEF1B2 strictly collaborate with eEF1D and eEF1G in the conversion of eEF1A from its inactive GDP-bound form to its active GTP-bound form and so it covers a role as a guanine nucleotide exchange factor (GEF) for eEF1A (Le Sourd et al., 2006; Browne and Proud, 2002).
It was shown that the nucleotide exchange reaction by eEF1B2 is inhibited by Mg2+ that binds on K205 residue. Only after the displacing of Mg2+ from its binding site eEF1B2 can function correctly (Pittmann et al, 2006).
In prokaryotes, the homolog of eEF1B2 is known as EF-Ts, while in eukaryotes it is known only one functional protein form with the reference sequence NP_001950.1 by 225 residues. It is found in the eEF1H protein complex and it shows many domains: in the carboxyl half terminal there is an EF-1 guanine nucleotide exchange domain (EF1-GNE domain / GEF) while in the amino half terminal there is a region called GST-C-eEF1b-like domain (Glutathione S-transferase C-terminal-like domain)(see figure.2).
The fold of the C-terminal domain of eEF1B2 is found very similar to that many ribosomal proteins, i.e. it shows two so-called split b-a-b motifs (Andersen et al, 2003). This region possesses nucleotide exchange activity and interacts with eEF1A (Le Sourd et al., 2006).
The non-catalytic N-terminal domain of eEF1B2, that interacts with the N-terminal domain of eEF1G (Le Sourd et al., 2006; van Damme et al, 1991), has a regulatory role on the eEF1B2 itself because it can interfere with the guanine nucleotide exchange activity located on the C-terminal domain. In fact, the non-catalytic N-terminal domain of eEF1B2 brings to the reduction in the overall rate of the guanine nucleotide exchange reaction mediated by eEF1B2. It is only thanks to the bond of eEF1B2 with eEF1G that this inhibitory effect is abolished (Trosiuk et al, 2016).
EEF1B2 interacts primarily with eEF1A1/ EEF1A2 and eEF1G but also with valyl -tRNA synthetase (Val-RS)(Le Sourd et al., 2006; Bec et al., 1994). Seems that there are no direct interactions between eEF1B2 and eEF1D (Cao et al, 2014; Sheu and Traugh, 1997), although different interactional models were proposed (Le Sourd et al., 2006; Jiang et al.,2005; Sheu and Traugh, 1999; Minella et al., 1998).
In addition, eEF1B2 interact with translationally controlled tumor protein (TCTP) but the nature of this interaction is still poorly understood (Wu et al, 2015).
Post-translational modifications. Some post-translational modifications are observed, such as phosphorylation and acetylation (https://www.ncbi.nlm.nih.gov). Phosphorylations of eEF1B2 are made by some protein kinases, including casein kinase 2 (CK2) (Browne and Proud, 2002).

eEF1B2 is expressed widely in human tissues (https://www.genecards.org) although its expression is not uniform in either tissues or cell lines (Cao et al, 2014).

eEF1B2 is located mostly in the cytoplasm but it was also found in the nucleus (https://www.genecards.org/cgi-bin/carddisp.pl?gene=EEF1B2). It shows a perinuclear distribution (Sanders et al, 1996) and it is found on the endoplasmic reticulum (Cho et al, 2003; Sanders et al, 1996).

eEF1B2 plays a fundamental role in the cell, in particular in the translation elongation step. In fact, eEF1B2 shows canonical functions and multiple non-canonical roles (moonlighting roles) inside the cell.
Canonical function: eEF1B2 binds to eEF1D and eEF1G in the eEF1B2DG macromolecular complex and contributes to catalyze the exchange of GDP/GTP for eEF1A during the translation elongation cycle. It was shown that eEF1B2 has the ability to disrupt eEF1A-induced actin organization and so engage eEF1A for protein synthesis (Pittman et al, 2009).
Non-canonical roles: eEF1B2 seems to have other functions inside the cell besides its involvement in translation. Together with eEF1D and eEF1G, it controls the translation fidelity (Le Sourd et al, 2006) and in response to stressors such as heat shock, oxidative stress, and toxins, it mediates the inhibition of protein synthesis. In addition, it seems to have interaction with the cytoskeleton (Khudhair et al., 2014), but the effect of eEF1B2 on actin filaments is still poorly understood (Sasikumar et al, 2012).

eEF1B2 is highly conserved and its homology between the species is reported in Table.3

Organism	Species	Symbol	DNA Identity (%)	PROT Identity (%)
Human	H.sapiens	EEF1B2	100	100
Chimpanzee	P.troglodytes	EEF1B2	99.9	100
Macaco	M.mulatta	EEF1B2	97.6	99.6
Wolf	C.lupus	EEF1B2	93.0	98.2
Cattle	B.taurus	EEF1B2	91.1	97.8
Mouse	M.musculus	Eef1b2	89.2	95.6
Rat	R.norvegicus	Eef1b2	89.2	94.7
Chicken	G.gallus	EEF1B2	82.0	93.3
Xenopus tropicalis	X.tropicalis	eef1b2	78.1	85.3
Zebrafish	D.rerio	eef1b2	73.8	82.6
Fruit fly	D.melanogaster	Ef1beta	58.7	58.8
Mosquito (Anopheles)	A.gambiae	AgaP_AGAP010612	60.2	62.0
Caenorhabditis	C.elegans	eef-1B.1	55.1	53.1

Table.3 EEF1B2 homology (reworked from htpps://www.ncbi.nlm.nih.gov/homologene)

A great number of mutations in the genomic sequence and in the amino acid sequence for EEF1B2 were discovered in cancer cells that are obviously genetically more unstable respect normal ones. The genomic alterations observed include the formation of novel fusion genes. However, there are no sufficient experimental data yet to understand the repercussions on cellular behaviour and so the implications in cancer of these alterations.