EEF1G/PPP6R3 (11q12-13)

2019-05-01   Luigi Cristiano 

1.Aesthetic and medical biotechnologies research unit, Prestige, Terranuova Bracciolini, Italy. -

(Note: the fusion was discovered by NGS. Many chromosome rearrangement mechanisms such as translocation, inversion,deletion or complex rearrangement may lead to the same fusion)


Analysis of the EEF1G/PPP6R3 fusion involving EEF1G (alias, eukaryotic translation elongation factor 1 gamma) gene and PPP6R3 (alias, protein phosphatase 6 regulatory subunit 3) gene. It was detected in lung squamous cell carcinoma.

Clinics and Pathology


Lung squamous cell carcinoma (lung SqCC) shows very complex genomic alterations with abundant exonic mutations, genomic rearrangements and gene copy number alterations. Some authors detected the presence of the EEF1G/PPP6R3 fusion deriving by the genomic translocation of a part of EEF1G gene with a portion of PPP6R3 gene, both located on chromosome 11 (Hammerman et al., 2012). Other fusion genes or abnormal chromosomal translocations detected for PPP6R3 in this cancer type are t(7;11)(q21;q13) CCDC132/PPP6R3, t(7;11)(q34;q13) PPP6R3/MGAM, t(7;11)(q34;q13)SSBP1/PPP6R3, and fusion genes PPP6R3/ARHGAP1, PPP6R3/CNTN5, and PPP6R3/LRP5 (Yoshihara et al., 2015; Hammerman et al., 2012;


There is no evidence of the impact of the EEF1G/PPP6R3 fusion gene on the tumour behaviour and so its contribution in the prognosis of lung squamous cell carcinoma is still unknown.

Genes Involved and Proteins

Gene name





Eukaryotic translation elongation factor 1 gamma, alias eEF1G, is a protein that play a main function in the elongation step of translation process but also cover numerous moonlighting roles. It is expressed ubiquitously in human tissues and often it is found over-expressed in human cancer samples and cancer cell lines.

Dna rna description

EEF1G (Eukaryotic Translation Elongation Factor 1 Gamma) is a protein coding gene with 10 exons and a length of 14388 bp (RefSeq NC_000011.10). Its transcript is 1446 bp long (RefSeq NM_001404.5) but was observed five splice variants and nine pseudogenes probably originated by retrotransposition.

Protein description

eEF1G is formed by 437 amino acids (RefSeq NP_001395.1), it has a molecular weight of 50.12 kDa and it is a multi-domain protein which consist of three main domains: from the amino to carboxyl half terminal there are a glutathione S-transferase (GST)-like N-terminus domain (NT-eEF1G), a glutathione S-transferase (GST)-like C-terminus domain (CT-eEF1G) and a conserved C-terminal domain (CD-eEF1G)(Achilonu et al.,2014).
eEF1G is a subunit of the eukaryotic elongation factor-1 complex named eEF1H that result by the aggregation of different proteins that play a central role in peptide elongation during eukaryotic protein biosynthesis. The physiological role of eEF1G is still not well defined, however eEF1G seems to be necessary for guarantee the stability to entire eEF1H complex and to stimulate the activity of the eEF1B2 subunit during the elongation step of translation (Mansilla et al., 2002). However, are known that it has multiple non-canonical roles (moonlighting roles) inside the cell such as the interaction with cytoskeleton and binding with various mRNA and several proteins, comprise membrane-bound receptors (Coumans et al., 2014; Corbi et al., 2010; Cho et al., 2003).

Gene name




Dna rna description

PPP6R3 is a protein coding gene of 154617 nt long (RefSeq NC_000011.10) and with an abundant number of alternative splicing variants, i.e. 38 coding mRNA and 24 non-coding mRNA.

Protein description

PPP6R3 counts 24 protein isoforms and is one of the three regulatory subunits of protein phosphatase 6 (PP6) complex (York et al., 2014; Guergnon et al., 2009) and has a sit4-associated protein domain, alias SAPS domain (Stefansson and Brautigan, 2006). It plays a role, as member of PP6 holoenzyme, in the turnover of serine and threonine phosphorylation events during mitosis acting as a regulatory element of the complex.

Result of the chromosomal anomaly


The result of chromosomal anomaly is the EEF1G/PPP6R3 fusion with the formation of a novel but not still characterized fusion gene 5 EEF1G - 3 PPP6R3. Hammerman and colleagues (Hammerman et al., 2012) found it in patients with lung squamous cell carcinoma (lung SqCC), but there are no data or evidence about its mRNA and/or its protein. So, in this review, with the use of Ensembl (, will be predicted the result of this rearrangement. However, the data collected and showed are hypothesis and have to be experimentally verified.
Atlas Image
Figure 1. Schematic representation of the EEF1G gene, PPP6R3 gene and the EEF1G-PPP6R3 fusion. [A] In the upper side of the picture there are the genomic sequences of EEF1G and PPP6R3 genes with the indication of DNA breakpoints individuated by Hammerman and colleagues (Hammerman et al., 2012); [B] in the bottom side of the picture are reported the genomic rearrangement on chromosome 11 and the predicted structure of the novel EEF1G/PPP6R3 fusion after the analysis with Ensembl ( In addition, there are also indicated the promoter/enhancer elements (reworked from


From the direct analysis of the gene sequences and the respective DNA breakpoints using Ensembl (, could be advanced the hypothesis that the chromosomal rearrangement where EEF1G and PPP6R3 are involved, although it was described as an intra-chromosomal translocation, it seems more similar to an inversion. Moreover the first breakpoint is located 236,453 nt before EEF1G gene while the second breakpoint is located just before PPP6R3 gene, i.e. 92,441 nt before PPP6R3 gene (Figure.1). This chromosomal rearrangement permits to bring near EEF1G to PPP6R3, reducing the long distance between them, i.e. from 5,886,730 nt (about 5,886 kb) to only 328,894 nt (about 328 kb). The reason of this rearrangement is unknown.


There is no evidence about the mRNA of the EEF1G/PPP6R3 fusion gene or other transcript resulting from the EEF1G/PPP6R3.


There is no evidence of protein from the EEF1G/PPP6R3 fusion gene.


The role in oncogenesis of the EEF1G/PPP6R3 fusion is unclear, and there is no evidence about its effective transcription and/or translation. Hammerman and colleagues (Hammerman et al., 2012) have supposed the presence of a fusion gene 5EEF1G - 3PPP6R3 but actually there are poor data about it and thus it is unclearly the role of this fusion gene, i.e. if is effectively translated into a functional protein or instead it plays a regulatory role. What it is clear is that PPP6R3 is involved in many and heterogeneous genomic translocations in different kind of tumors as EEF1G that is involved in numerous genomic alterations such as translocations and in novel fusion genes. Both genes are important for cell biology and it is normal that they are subjected to rearrangements in cancer cells. In addition, this could happens also for the characteristics of their promoters because at least for PPP6R3 it is known that it possess a potent promoter activity (Guo et al., 2016). However, the truly oncogenic potential of EEF1G/PPP6R3 in proliferation and cancer aggressiveness needs to be better elucidated.


Pubmed IDLast YearTitleAuthors
247325822014Purification and characterisation of recombinant human eukaryotic elongation factor 1 gamma.Achilonu I et al
145194482003Direct and biochemical interaction between dopamine D3 receptor and elongation factor-1Bbetagamma.Cho DI et al
212178132010The eEF1γ subunit contacts RNA polymerase II and binds vimentin promoter region.Corbi N et al
238996272014Green fluorescent protein expression triggers proteome changes in breast cancer cells.Coumans JV et al
198356102009Mapping of protein phosphatase-6 association with its SAPS domain regulatory subunit using a model of helical repeats.Guergnon J et al
271132712016PPP6R3-USP6 amplification: Novel oncogenic mechanism in malignant nodular fasciitis.Guo R et al
229607452012Comprehensive genomic characterization of squamous cell lung cancers.
119854942002Mapping the human translation elongation factor eEF1H complex using the yeast two-hybrid system.Mansilla F et al
167697272006Protein phosphatase 6 subunit with conserved Sit4-associated protein domain targets IkappaBepsilon.Stefansson B et al
251875372014Interactome analysis of the influenza A virus transcription/replication machinery identifies protein phosphatase 6 as a cellular factor required for efficient virus replication.York A et al
255005442015The landscape and therapeutic relevance of cancer-associated transcript fusions.Yoshihara K et al


Luigi Cristiano

EEF1G/PPP6R3 (11q12-13)

Atlas Genet Cytogenet Oncol Haematol. 2019-05-01

Online version:

Historical Card

0000-00-00 t(11;11)(q12;q13) EEF1G/PPP6R3 by  Jean-Loup Huret,Philippe Dessen,Jean-Loup Huret,Philippe Dessen