EEF1D (eukaryotic translation elongation factor 1 delta)

2019-05-01   Luigi Cristiano, MSc 

Aesthetic and medical biotechnologies research unit, Prestige, Terranuova Bracciolini, Italy; prestige.infomed@gmail.com; luigicristiano@libero.it

Identity

HGNC
EEF1D
LOCATION
8q24.3
LOCUSID
1936
ALIAS
EF-1D,EF1D,FP1047

Abstract

Eukaryotic translation elongation factor 1 delta, alias EEF1D, is a protein-coding gene that plays a role in the elongation step of translation and considering its importance it is found frequently overexpressed in human cancer cells. This review collects the data on DNA\/RNA, on the protein encoded and on the diseases where EEF1D is involved.

DNA/RNA

Atlas Image
Figure. 1. EEF1D gene and splicing variants/isoforms. The figure shows the locus on chromosome 8 of the EEF1D gene (reworked from https://www.ncbi.nlm.nih.gov/gene; http://grch37.ensembl.org; www.genecards.org)

Description

EEF1D (Eukaryotic Translation Elongation Factor 1 delta) is a protein-coding gene that starts at 143,579,722 nt and ends at 143,597,675 nt from pter. It has a length of 17,954 bp and the current reference sequence is NC_000008.11. It is proximal to the NAPRT (nicotinate phospho-ribosyl-transferase domain containing 1) gene and TIGD5 (tigger transposable element derived 5) gene. Around the genomic locus of EEF1D there are different promoter or enhancer transcriptional elements. Two strong of these elements are closer to the sequence of EEF1D gene and are located at +1.6 kb and at -1.2 kb respectively.

Transcription

Several alternative splicing transcript variants for EEF1D were observed and they encode multiple eEF1D isoforms. Their main characteristics are reported in Table.1 . The main reference sequence is NM_032378.5 that corresponds to the variant 1 of EEF1D mRNA, alias EEF1D-205 or EEF1D-001, and it is 2,473 bp long. The 5UTR counts 459 nt, the CDS is extended from 460 to 2,403 nt, while the 3UTR covers the last 70 nt.
NameVariantRefSeq (1)Transcript IDExonsTypeLenght (bp)IsoformAliasRefSeq (2)Lenght (aa)MW (kDa)pI
EEF1D-204Var.3NM_001130053ENST00000423316.69protein coding2356Isoform 1-NP_00112352564771.426.02
EEF1D-205 (EEF1D-001)Var.1NM_032378ENST00000442189.610protein coding2473Isoform 1-NP_11575464771.426.02
EEF1D-201Var.6NM_001130057ENST00000317198.108protein coding1458Isoform 2-NP_00112352928131.124.90
EEF1D-203Var.5NM_001130055ENST00000419152.6 9protein coding1427Isoform 2-NP_00112352728131.124.90
EEF1D-225  (EEF1D-006)--ENST00000529272.58protein coding1311---281--
EEF1D-202  (EEF1D-002)Var.9NM_001289950ENST00000395119.78protein coding1428Isoform 2-NP_00127687928131.124.90
Var.2NM_0019601251Isoform 2-NP_00195128131.124.90
EEF1D-207 (EEF1D-053)--ENST00000524624.58protein coding1084---257--
EEF1D-218  (EEF1D-005)Var.8NM_001195203ENST00000526838.58protein coding1194Isoform 5-NP_00118213226229.074.91
EEF1D-223  (EEF1D-004)Var.7NM_001130056 ENST00000528610.57protein coding1179Isoform 4-NP_00112352825728.564.81
Var.10NM_0013177431176Isoform 4-NP_00130467225728.564.81
Var.11NM_0013306461386Isoform 4-NP_00131757525728.564.81
EEF1D-246 (EEF1D-007)--ENST00000532741.58protein coding2387---697--
EEF1D-256--ENST00000618139.210protein coding2238---631--
EEF1D-232 (EEF1D-017)--ENST00000530445.55protein coding1217---166--
EEF1D-253 (EEF1D-048)--ENST00000534380.58protein coding1001---261--
EEF1D-216 (EEF1D-040)--ENST00000526710.11protein coding996---300--
EEF1D-239 (EEF1D-034)--ENST00000531670.53protein coding926---179--
EEF1D-230 (EEF1D-032)--ENST00000530191.55protein coding853---204--
EEF1D-247 (EEF1D-047)--ENST00000533204.57protein coding842---204--
EEF1D-238 (EEF1D-020)--ENST00000531621.57protein coding840---238--
EEF1D-208 (EEF1D-037)--ENST00000524883.12protein coding828---180--
EEF1D-237 (EEF1D-035)--ENST00000531281.12protein coding813---257--
EEF1D-244 (EEF1D-033)--ENST00000532543.12protein coding791---39--
EEF1D-236 (EEF1D-046)--ENST00000531218.57protein coding787---198--
EEF1D-215 (EEF1D-039)--ENST00000526340.56protein coding770---63--
EEF1D-245 (EEF1D-042)--ENST00000532596.53protein coding761---190--
EEF1D-248 (EEF1D-045)--ENST00000533494.57protein coding758---168--
EEF1D-234 (EEF1D-011)--ENST00000530616.56protein coding749---210--
EEF1D-249 (EEF1D-052)--ENST00000533749.55protein coding633---137--
EEF1D-252 (EEF1D-049)--ENST00000534377.55protein coding617---187--
EEF1D-233 (EEF1D-027)--ENST00000530545.53protein coding616---84--
EEF1D-241 (EEF1D-024)--ENST00000531931.12protein coding614---35--
EEF1D-210 (EEF1D-050)--ENST00000525223.12protein coding610---39--
EEF1D-228 (EEF1D-043)--ENST00000529832.53protein coding600---146--
EEF1D-231 (EEF1D-041)--ENST00000530306.53protein coding583---129--
EEF1D-211 (EEF1D-031)--ENST00000525261.53protein coding559---81--
EEF1D-220 (EEF1D-026)--ENST00000528303.54protein coding558---21--
EEF1D-255 (EEF1D-029)--ENST00000534804.54protein coding555---68--
EEF1D-222 (EEF1D-036)--ENST00000528519.12protein coding553---157--
EEF1D-254 (EEF1D-030)--ENST00000534475.54protein coding538---31--
EEF1D-214 (EEF1D-038)--ENST00000526135.53protein coding535---53--
EEF1D-229 (EEF1D-014)--ENST00000530109.53protein coding533---156--
EEF1D-242 (EEF1D-021)--ENST00000531953.53protein coding506---49--
EEF1D-226 (EEF1D-019)--ENST00000529516.56protein coding473---139--
EEF1D-227 (EEF1D-015)--ENST00000529576.53protein coding424---119--
EEF1D-243 (EEF1D-016)--ENST00000532400.14protein coding419---99--
EEF1D-213 (EEF1D-022)--ENST00000526133.12protein coding367---36--
EEF1D-209 (EEF1D-044)--ENST00000524900.13protein coding343---62--
EEF1D-221 (EEF1D-013)--ENST00000528382.13protein coding308---36--
EEF1D-206--ENST00000524397.58nonsense md957------
EEF1D-224--ENST00000529007.58nonsense md861------
EEF1D-250--ENST00000533833.57nonsense md831------
EEF1D-240--ENST00000531770.54processed transcript589------
EEF1D-219--ENST00000527741.54retained intron3718------
EEF1D-217 --ENST00000526786.56retained intron1246------
EEF1D-212 --ENST00000525695.53retained intron907------
EEF1D-251 --ENST00000534232.56retained intron817------
EEF1D-235--ENST00000530848.55retained intron688------

Table.1 Alterative splicing variants and isoforms of EEF1D.  (reworked from http://grch37.ensembl.org; ttps://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

Pseudogene

According to Entrez Gene, the analysis of the human genome revealed the presence of several pseudogenes for EEF1D (Table.2) classified as processed pseudogenes and probably originated by retrotransposition. 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.
Little more characterized are EEF1DP3 and EEF1DP4 pseudogenes respect the others. What is known is that these two pseudogenes are probably involved in human cancers or in other diseases. Especially EEF1DP3 was found in some genomic rearrangements with the formation of hybrid genes among which the most studied is EEF1DP3/FRY (Kim et al., 2015).
GeneGene  nameGene IDRefSeqLocusLocationStartEndLenght (nt)Main diseases/td>Reference
EEF1DP1EEF1D pseudogene 1126037NC_000019.10 Chromosome 1919p13.121407032514071304980Large B-cell lymphoma (?)-
Myeloid leukemia (?)-
EEF1DP2EEF1D pseudogene 2442429NC_000009.12 Chromosome 99q22.319283676692837741976Melanoma (?)-
EEF1DP3EEF1D pseudogene 3196549NC_000013.11 Chromosome 1313q13.13184678331959584112802Prostate carcinomaErho et al., 2012
 Breast carcinomaKim et al., 2015
Ankylosing spondylitisShahba et al., 2018
Melanoma (?)-
Non-small cell lung cancer (?)-
Multiple sclerosis (?)-
Large B-cell lymphoma cell lines (SUDHL4, Toledo, OCI-Ly3)(?)-
Lung adenocarcinoma (?)-
Epidermolysis Bullosa Simplex (?) 
EEF1DP4EEF1D pseudogene 4442325NC_000007.14 Chromosome 77q11.2164862951648644501500Glioma (?)-
Breast carcinoma (?)-
Primary myelofibrosis (?)-
Osteosarcoma (?)-
EEF1DP5EEF1D pseudogene 5442258NC_000006.12 Chromosome 66q22.33128580065128580952888 Breast carcinomaStefansson et al., 2011
EEF1DP6EEF1D pseudogene 6644357NC_000001.11 Chromosome 11p36.3241754634175899437--
EEF1DP7EEF1D pseudogene 7100422656NC_000017.11 Chromosome 1717q23.36363660163637110510--
EEF1DP8EEF1D pseudogene 8283236NC_000011.10 Chromosome 1111q12.36216921962169827609--

Table.2 EEF1D pseudogenes (reworked from https://www.ncbi.nlm.nih.gov/gene/1937; https://www.targetvalidation.org; https://www.ncbi.nlm.nih.gov/geoprofiles/) [ (?) ] uncertain;  [ - ] no reference

Proteins

Atlas Image
Figure.2 eEF1D protein isoforms. Graphical representation of eEF1D protein isoforms with the highlight of the main verified post-translational modifications (reworked from Kaitsuka et al., 2015; Kaitsuka et al., 2011; http://grch37.ensembl.org; https://www.ncbi.nlm.nih.gov; https://www.uniprot.org/uniprot/P29692; http://bioinf.umbc.edu/dmdm/gene_prot_page.php).

Description

The eukaryotic translation elongation factor 1 delta (alias eEF1D, eEF1delta;, eEF1Bdelta;) is a subunit of the macromolecular eukaryotic translation elongation factor-1 complex (alias eEF1, also called eEF1H), a high-molecular-weight form made up of an aggregation of different protein subunits: EEF1A (alias eEF1α), EEF1B2 (alias eEF1Β, eEF1Bα, eEF1B2), EEF1G (alias eEF1γ, heEF1γ, eEF1Bγ), EEF1D and valyl t-RNA synthetase ( VARS). 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 mediated the GTP hydrolysis. Thus eEF1BGD-complex acts as a guanine nucleotide exchange factor (GEF) regenerating eEF1A-GTP for the successive elongation cycle. The physiological role of eEF1D in the translation context is still not well defined, however eEF1D seems to strictly collaborate with eEF1B 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).
There are known four isoforms produced by alternative splicing: the isoform 1 (RefSeq NP_001123525 or NP_115754), also called eEF1DL or eEF1Bdelta;L, is the longest isoform that also has been chosen as the canonical sequence and it is formed by 647 residues. It is found in the eEF1H protein complex and it shows many domains: in the carboxyl half terminal there are an acidic region and an EF-1 guanine nucleotide exchange domain (EF1-GNE domain / GEF) while in the amino half terminal there are a highly-conserved leucine-rich zipper-like region (aa 184-225), a basic region (aa 272-294) and a nuclear localization signal (NLS)(Kaitsuka et al., 2015; Kaitsuka et al., 2011; Sanders et al., 1993). The basic region seems to be involved in DNA binding while the leucine zipper region may be a protein interaction domain. However, the exact functional role of these regions is unclear (Kaitsuka et al., 2015). The N-terminal domain of eEF1D interacts with the NT-eEF1G domain of eEF1G (Cao et al., 2014; Mansilla et al., 2002; Janssen et al., 1994) but there are no interactions between eEF1D and eEF1B (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).
The long isoform of eEF1D (eEF1DL) interacts with HSF1 and NFE2L2 (NRF2) proteins into the nucleus (Kaitsuka et al., 2011; https://www.genecards.org) and regulates induction of heat-shock-responsive genes, such as HSPA6, CRYAB, DNAJB1 and HO-1, through the association with the heat shock transcription factors and with a direct DNA-binding at heat shock promoter elements (HSE) (Kaitsuka et al., 2015; Kaitsuka et al., 2011; https://www.uniprot.org/uniprot/P29692).
The isoform 2, with 281 amino acids, is smaller and, as the isoform 1, it is a multi-domain protein which consists of three main domains: from the amino to carboxyl half terminal there are an N-terminal leucine zipper domain, a C-terminal acidic region and a C-terminal domain that shows GDP/GTP exchange activity (GEF)( Kaitsuka et al., 2015; Kaitsuka et al., 2011). The roles of the isoform 4 and isoform 5 are still undefined.
All isoforms have many interaction surface points with the eukaryotic translation elongation factor 1 alpha (eEF1A) protein (https://www.ncbi.nlm.nih.gov/protein/ NP_001123525) and interact with the valyl -tRNA synthetase (Val-RS)(Le Sourd et al., 2006; Bec et al., 1994).
EEF1D interacts with SIAH1, an E3 ubiquitin protein ligase involved in the regulation of cell cycle, tumorigenesis and also in the initiation of neurodegenerative diseases. Is reported that the overexpression of EEF1D is linked with an increase in SIAH-1 levels due to the inhibition of its autoubiquitination and thus of its degradation (Wu et al., 2011). In addition, EEF1D is an interaction partner of kinectin that function as the membrane anchor for EEF1D on the endoplasmic reticulum (Ong et al., 2003)
Post-translational modifications. Some post-translational modifications are observed, such as phosphorylation, acetylation and succinylation (https://www.ncbi.nlm.nih.gov). eEF1D can be hyperphosphorylated and the phosphorylations are made by some protein kinases, including casein kinase 2 (Gyenis et al., 2011; Browne and Proud, 2002) and cyclin-dependent kinase 1 ( CDK1) (Kawaguchi et al., 2003). In particular, CDK1 phosphorylates EEF1D at Ser-133 (Kawaguchi et al., 2003).
In addition, eEF1D can be found hyperphosphorylated by viral protein kinases after alpha-, beta-, and gammaherpesviruses infections (Kawaguchi et al., 2003).
Atlas Image
Figure 3. The translation elongation mechanism. The active form of eukaryotic translation elongation factor 1 alpha (eEF1A) in complex with GTP delivers an aminoacylated tRNA to the A site of the ribosome. Following the proper codon-anticodon recognition the GTP is hydrolyzed and the inactive eEF1A-GDP is released from the ribosome and then it is bound by eEF1B2GD complex forming the macromolecular protein aggregate eEF1H. eEF1H is formed previously by the binding of three subunits: eEF1B2, eEF1G and eEF1D. This complex promotes the exchange between GDP and GTP to regenerate active form of eEF1A (reworked from Dongsheng et al., 2013; Ejiri, 2002; Riis et al, 1990; https://reactome.org)

Expression

eEF1D is expressed widely in human tissues and high levels of protein are reported in bone marrow stromal cells (https://www.genecards.org). The long form of eEF1D (eEF1DL) is found to be highly expressed in brain and testis (Kaitsuka et al., 2011).

Localisation

eEF1D is located mostly in the cytoplasm but it is also found in the nucleus, especially its long form (Kaitsuka et al., 2011), and also in relation with the endoplasmic reticulum (Sanders et al., 1996).
Atlas Image
Figure 4. Subcellular localization of eEF1D. Cytoplasmic and nuclear localizations for eEF1D were determined by transfection experiments with GFP-eEF1D fusion proteins for both isoforms (GFP-eEF1D and GFP-eEF1DL) in HeLa cells. The tests were made by confocal microscopy with a scale bar of 20 m. eEF1D was found also in relation to the endoplasmic reticulum (ER) in primary fibroblasts VH25 cells. The long form of EEF1D (EF1DL) is the only isoform that is found also in nucleus, while in the cytoplasm and on ER co-localize both long and short isoforms (reworked from Kaitsuka et al., 2011; Sanders et al., 1996. Note: some picture elements were obtained from using BioRender illustration tool).

Function

eEF1D has shown to cover an important role in normal brain functioning and development and some experiments on KO mice lacking the expression of its long isoform (eEF1DL) have done emerging its implication for normal physiology of the brain. In fact, in these KO mice were observed severe seizures in response to loud sounds and also significant brain structure alterations such as a decrease in brain weight, atrophy of the hippocampus and midbrain and a reduction of cortical layer thickness (Kaitsuka et al., 2018).
eEF1D shows canonical functions and multiple non-canonical roles (moonlighting roles) inside the cell.
Canonical function: eEF1D binds to eEF1B and eEF1G in the eEF1BDG macromolecular complex and contributes to catalyze the exchange of GDP/GTP for eEF1A during the translation elongation cycle.
Non-canonical roles: eEF1D seems to have other functions inside the cell besides its involvement in translation. At least two other non-canonical roles have been detected, i.e. its role as a transcriptional factor and its involvement in the stress response. These roles are closely connected to each other. In fact, it was demonstrated that heat shock induces the splicing-dependent expression change from the short eEF1D isoform (isoform 2) to the eEF1DL long isoform (isoform 1)(Kaitsuka et al., 2015). The silencing of eEF1DL inhibits the stress responses suggesting its role in the modulation of stress response in the cell (Hensen et al., 2013). In fact, EEF1D is a heat shock transcription factor that can bind to the heat shock element (HSE) in the promoter of the HSPA6 and HO-1 genes and activate their transcription (Kaitsuka et al., 2011).

Homology

eEF1D is highly conserved and its homology between the species is reported in Table.3
OrganismSpeciesSymbol DNA Identity (%)PROT Identity (%)
HumanH.sapiensEEF1D100100
ChimpanzeeP.troglodytesEEF1D99.699.3
MacacoM.mulattaEEF1D95.795.7
WolfC.lupus LOC47511585.285.5
CattleB.taurusEEF1D92.188.3
Mouse M.musculusEef1d85.284.3
RatR.norvegicusEef1d86.884.5
ChickenG.gallusEEF1D57.761.6
Xenopus tropicalisX.tropicaliseef1d67.869.7
Zebrafish D.rerioeef1db65.866.3
Fruit flyD.melanogastereEF1delta55.657.0
Mosquito (Anopheles)A.gambiaeAgaP_AGAP00423548.557.0
 Caenorhabditis C.eleganseef-1B.253.857.6

Table.3 EEF1D homology (reworked from ps://www.ncbi.nlm.nih.gov/homologene)

Mutations

Note

A great number of mutations in the genomic sequence and in the amino acid sequence for EEF1D 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 fusion genes.
Atlas Image
Figure 5. Circos plot for fusion events involving eEF1D. The picture summarizes all fusion events concerning eEF1D and its fusion partners (from https://fusionhub.persistent.co.in/search_genewise.html).

Implicated in

Top note
EEF1D is a cellular proto-oncogene (Joseph et al., 2002) and it is involved in many and heterogeneous genomic translocations in different kind of tumors with also the creation of numerous fusion gene (Table.4). An increase of its expression level has an oncogenic potential with resulting in cell transformation (Lei et al., 2002) and this was observed in many cancer types (Hassan et al., 2018). In addition, the use of antisense mRNA to block EEF1D translation can revert its oncogenic potential (Lei et al., 2002). These data could suggest its role as a potential diagnostic indicator and prognostic marker in tumors (Joseph et al., 2002). EEF1D/SDC4EEF1DSDC48q24.3 20q13.12t(8;20)(q24;q13)TranslocationAdenocarcinomaProstatePRADWu et al., 2012
TATDN1/EEF1DTATDN1EEF1D8q24.138q24.3t(8;8)(q24;q24)Fusion geneAdenocarcinoma BreastBRCA- Laryngeal cancerHead and Neck HNSCTao et al., 2018 Cell lineCa SkiKlijn et al., 2015 EEF1D/KRT6AEEF1DKRT6A8q24.3 12q13.13t(8;12)(q24;q13)TranslocationSquamous Cell CarcinomaHead and Neck HNSCKlijn et al., 2015 EEF1D/KRT14EEF1DKRT148q24.3 17q21.2t(8;17)(q24;q21)TranslocationSquamous Cell CarcinomaUterine cervixCESCAlaei-Mahabadi et al., 2016 EEF1D/NAPRTEEF1DNAPRT8q24.38q24.3Readthrough transcriptionFusion gene-Cell lineESCBabiceanu et al.,2016 SCRIB/EEF1DSCRIBEEF1D8q24.38q24.3t(8;8)(q24;q24)Fusion geneSerous CystadenocarcinomaOvaryOVSC- EEF1D/TSTA3 EEF1DTSTA3 8q24.38q24.3t(8;8)(q24;q24)Fusion geneAdenocarcinomaLungLUAD Yoshihara et al 2015 PMF1/EEF1DPMF1EEF1D1q228q24.3t(1;8)(q22;q24)Translocation-Cell lineRT4Klijn et al., 2015 IGLL5/EEF1DIGLL5EEF1D22q11.228q24.3t(8;22)(q24;q11)Translocation-Cell lineMOLP-8Klijn et al., 2015 ZC3H3/EEF1DZC3H3EEF1D8q24.38q24.3t(8;8)(q24;q24)Fusion gene-Bone marrow-Babiceanu et al.,2016 Table.4 EEF1D rearrangements: translocations and fusion genes (reworked from ps://www.ncbi.nlm.nih.gov/homologene; http://www.tumorfusions.org; https://cgap.nci.nih.gov/Chromosomes; http://quiver.archerdx.com; http://atlasgeneticsoncology.org//Bands/8q24.html#REFERENCES; https://fusionhub.persistent.co.in/home.html; https://ccsm.uth.edu/FusionGDB/index.html) [ (?) ] unknown;  [ - ] no reference
Entity name
Amyotrophic lateral sclerosis (ALS)
Note
EEF1D is a potential candidate gene associated with ALS (Wain et al., 2009) but more studies are needed to clarify its effective contribution.
Entity name
Bladder cancer
Note
There are no data about EEF1D expression alterations in bladder cancer. However, it was reported the translocation t(1;8)(q22;q24) PMF1/EEF1D (Klijn et al., 2015).
Hybrid gene
The t(1;8)(q22;q24) PMF1/EEF1D was detected in bladder transitional-cell carcinoma RT4 cell line (Klijn et al., 2015). This rearrangement is originated by the fusion of "polyamine modulated factor 1" ( PMF1) gene at 5-end with EEF1D gene at 3 end. There are no data about its chimeric transcript or protein and the role of this genomic alteration is poorly understood.
Entity name
Brain and central nervous system (CNS) cancers
Note
EEF1D is found to be overexpressed in astrocytoma and in glioblastoma samples and also in low-risk patients. This may associate its expression to favourable survival outcome (Hassan et al., 2018).
Entity name
Breast cancer
Note
EEF1D is involved in breast cancer (Jurca et al., 2016). In fact, was detected an EEF1D gene copy number gain in BT483, EFM19, HCC1143, HCC1395, HCC1569, HCC1806, HCC1937, HCC2157, HCC2218, HDQP1, MDAMB436 and UACC893 breast cancer cell lines and in about 10% of breast invasive carcinoma donor samples (http://www.oasis-genomics.org/). EEF1D was found overexpressed in T-47, MCF-7, MDA-MB-361 and MDA-MB-453 breast cancer cell lines (Joseph et al., 2004). It is also overexpressed in breast cancer samples and this predicted worse relapse-free survival (RFS) in luminal A subtype patients and poor overall survival (OS) and RFS in basal subtype (Hassan et al., 2018).
Some authors have found an EEF1D downregulation in ER+/ER- cancer cell lines and in human breast cancer samples when high levels of bone morphogenetic protein-6 ( BMP6) are expressed (Yang et al., 2007). This seems to be linked with the prevention of eEF1D-induced breast cancer metastasis. In fact, EEF1D is a candidate protein marker of human brain metastasis in primary breast tumors (Sanz-Pamplona et al., 2011; vant Veer et al., 2002). In addition, some fusion genes and genomic translocations were reported (https://fusionhub.persistent.co.in/home.html).
Hybrid gene
The translocation t(8;22)(q24;q13) PLA2G6/EEF1D was found in breast carcinoma (BRCA) and consists by the fusion of phospholipase A2 group VI (< CC: TXT: PLA2G6 ID: 45836>) gene at 5-end with EEF1D gene at 3 end. In addition, other uncharacterized and rare rearrangements due to the translocation t(8;8)(q24;q24) are reported, i.e. the RPL30 /EEF1D and TATDN1/EEF1D fusion genes (https://fusionhub.persistent.co.in/home.html). In particular, the t(8;8)(q24;q24) RPL30 /EEF1D brings to the formation of a transcript composed by the exons 1 to 3 of RPL30 joined with exons 2 to 7 of EEF1D (http://203.255.191.229:8080/chimerdbv31/chimerseq_link.cdb?gene_pair=RPL30_EEF1D), while the t(8;8)(q24;q24) TATDN1/EEF1D brings to the formation of a transcript composed by the exon 1 of TATDN1 joined with exons 2 to 7 of EEF1D (http://203.255.191.229:8080/chimerdbv31/chimerseq_link.cdb?gene_pair=TATDN1_EEF1D). Despite what has just been said, these genomic alterations are still poorly understood.
Entity name
Chondrosarcoma
Note
The human chondrosarcoma cells are able to respond to mechanical stimuli, like cellular stretching, with different phosphorylation events. Increase of phosphorylations impacts also on the EEF1D protein. It is unclearly the significance or the effect on the cell of these phosphorylations as also if these changes may affect the level or speed of protein synthesis (Pitti et al., 2008).
Entity name
Colorectal cancer
Note
It was detected an EEF1D gene copy number gain in LS123 and RKO colorectal cancer cell lines and in about 5% of colon adenocarcinoma donor samples (http://www.oasis-genomics.org/). In addition, EEF1D transcript is found to be significantly overexpressed (Hassan et al., 2018), especially in the right-sided colon cancer (RSCC) respect left-sided colon cancer (LSCC) samples (Shen et al., 2013). It was reported the translocation t(8;13)(q24;q13) UFM1/EEF1D (https://fusionhub.persistent.co.in/home.html).
Hybrid gene
The t(8;13)(q24;q13) UFM1/EEF1D was found in colon adenocarcinoma. This rearrangement is originated by the fusion of ubiquitin fold modifier 1 ( UFM1) gene at 5-end with EEF1D gene at 3 end. There are no data about the respective chimeric transcript or protein and the role of this genomic alteration is unknown.
Entity name
Gastric cancer
Note
It was detected an EEF1D gene copy number gain in 2313287, LMSU, MKN1, SNU5, SNU216, SNU601 and SNU668 gastric cancer cell lines (http://www.oasis-genomics.org/) but it was found down-expressed in gastric cancer samples (Hassan et al., 2018). Some fusion genes and genomic translocation are reported (Klijn et al., 2015; https://fusionhub.persistent.co.in/home.html).
Hybrid gene
The t(8;22)(q24;q11) IGLL5/EEF1D was found in gastric adenocarcinoma samples (Klijn et al., 2015) and consists by the fusion of immunoglobulin lambda-like polypeptide 5 ( IGLL5) gene at 5-end with EEF1D gene at 3 end. In addition, other uncharacterized and rare rearrangements are reported, i.e. OPLAH/EEF1D fusion gene and t(8;9)(q24;q22) EEF1D/ANKRD19P (https://fusionhub.persistent.co.in/home.html). In particular, the t(8;9)(q24;q22) EEF1D/ANKRD19P brings to the formation of a new chimeric gene with a transcript formed by the exons 1 to 5 of EEF1D joined with exon 10 of ankyrin repeat domain 19 pseudogene ( ANKRD19P). The protein resulting from this rearrangement lacks the GEF domain in the C-terminal (http://203.255.191.229:8080/chimerdbv31/chimerseq_link.cdb?gene_pair=EEF1D_ANKRD19P). Despite what has just been said, these genomic alterations are still poorly understood.
Entity name
Head and neck squamous cell carcinoma (HNSC)
Note
EEF1D gene was found up-regulated in head and neck squamous cell carcinoma (HNSC) (Hassan et al., 2018; Han et al., 2009). In particular, Flores and colleagues (Flores et al., 2016) detected its overexpression in oral squamous cell carcinoma (OSCC) respect to oral healthy mucosa. It could have a critical role both in cell proliferation and in epithelial-mesenchymal transition (EMT). In fact, EEF1D knockdown shown a decrease in cell cycle rate and proliferation. Some fusion genes and genomic translocation are reported (Klijn et al., 2015).
In addition, EEF1D was found up-regulated in human laryngeal cancer (Peyvandi et al., 2018) and was found an intrachromosomal translocation with the formation of a chimeric fusion gene between EEF1D and NAPRT1 genes in laryngeal cancer (Tao et al., 2018).
Hybrid gene
The t(8;12)(q24;q13) EEF1D/KRT5 and the t(8;12)(q24;q13) EEF1D/KRT6A were found in head and neck squamous cell carcinoma (HNSC) samples with the production of chimeric genes originated by the fusion of EEF1D at 5-end with keratin 5 ( KRT5) or keratin 6A ( KRT6A) genes at 3 end (Klijn et al., 2015). In addition, it was detected in laryngeal cancer the fusion gene 5 EEF1D - 3 NAPRT (Tao et al., 2018) that is probably originated by readthrough transcription, a known mechanism into the cell (He et al., 2018). In fact, EEF1D and NAPRT1 are two neighboring genes on the same chromosome.
The roles of all these genomic alterations are unknown.
Entity name
Kidney cancer
Note
High EEF1D mRNA levels were found in renal Wilms tumor and in clear cell carcinoma (Hassan et al., 2018). Some authors have detected missense mutations of EEF1D in papillary renal cell carcinoma (PRCC)(Liu et al., 2015). These mutations could contribute to the pathogenic mechanism for PRCC but more studies are necessary.
Entity name
Liver cancer
Note
EEF1D was found overexpressed in moderately to poorly differentiated (M/P-) primary human hepatocellular carcinoma (HCC) tissues (Hassan et al., 2018; Shuda et al., 2000). In addition, it was found the EEF1D/NAPRT fusion gene (https://fusionhub.persistent.co.in/home.html; https://ccsm.uth.edu/FusionGDB/index.html).
Hybrid gene
The EEF1D/NAPRT fusion gene was found in hepatocellular carcinoma (LIHC). This rearrangement is originated by the fusion of EEF1D gene at 5-end with nicotinate phosphoribosyltransferase domain containing 1 (NAPRT) gene at 3 end and it is probably due to readthrough transcription. In fact, EEF1D and NAPRT1 are two neighboring genes on the same chromosome. There are no data about the respective chimeric transcript or protein and the role of this genomic alteration is unknown.
Entity name
Lung cancer
Note
EEF1D was found to be down-expressed in lung carcinoid tumor and not shows any correlation with survival parameters (Hassan et al., 2018). It was also found down-expressed in adriamycin-resistant variants of DLKP squamous lung cancer cell line (Keenan et al., 2009). On the contrary, other authors found overexpression of EEF1D mRNA in some adenocarcinoma of the lung and squamous lung cell carcinoma tissue samples (Varemieva et al., 2014). In addition, eEF1D was found both in the cytoplasm and in the nucleus of lung adenocarcinoma A549 cell line (Varemieva et al., 2014) and the EEF1D/TSTA3 fusion gene was reported for lung adenocarcinoma (LUAD)(Yoshihara et al 2015).
Hybrid gene
The EEF1D/TSTA3 fusion gene was found in lung adenocarcinoma (LUAD) samples (Yoshihara et al 2015). This rearrangement is originated by t(8;8)(q24;q24) i.e. from the fusion of EEF1D gene at 5-end with tissue specific transplantation antigen P35B ( TSTA3) gene at 3 end. In particular, this rearrangement brings to the formation of a transcript composed by the exon 1 of EEF1D joined with exons 4 to 11 of TSTA3 (http://203.255.191.229:8080/chimerdbv31/chimerseq_link.cdb?gene_pair=EEF1D_TSTA3). Despite what has just been said, this genomic alteration is still poorly understood.
Entity name
Lymphoma and other blood cancers
Note
EEF1D is significantly overexpressed in different lymphoma subtypes, i.e. ALK-negative/ ALK positive anaplastic large cell lymphomas, Hodgkins lymphoma, acute adult T-cell leukaemia/lymphoma, Burkitts lymphoma, follicular lymphoma and diffuse large B-cell lymphoma (Hassan et al., 2018). Some fusion genes and genomic translocation were reported (Klijn et al., 2015; https://fusionhub.persistent.co.in/home.html; https://ccsm.uth.edu/FusionGDB/index.html).
Cytogenetics
The t(8;19)(q24;q13) EEF1D/ SPIB, t(8;17)(q24;q21) HDAC5/EEF1D, t(8;19)(q24;q13) RPS9/EEF1D, t(7;8)(q22;q24) SH2B2/EEF1D, t(8;19)(q24;q13) SPIB/EEF1D translocations and EEF1D/NAPRT fusion gene were reported for Burkitts lymphoma (BL). In addition, the t(8;22)(q24;q11) IGLL5/EEF1D was observed in multiple myeloma MOLP-8 cell line (Klijn et al., 2015). There are no data about the respective chimeric transcripts or proteins and the role of these genomic alterations is unknown.
Entity name
Medulloblastoma / Ependymoma
Note
EEF1D is overexpressed in medulloblastoma samples and it is adversely associated with overall and progression-free survival regardless of cytogenetic profile (De Bortoli et al., 2006). In addition, EEF1D was found highly expressed in ependymoma and this is related to poor outcome (de Bont et al., 2008).
Entity name
Melanoma
Note
EEF1D was found overexpressed in human chemoresistant melanoma cell lines (Sinha et al., 2000) and it was reported the translocation t(8;17)(q24;q25) FAM104A/EEF1D (Klijn et al., 2015).
Hybrid gene
The t(8;17)(q24;q25) FAM104A/EEF1D was reported in COLO794 cell line (Klijn et al., 2015). This rearrangement is originated by the fusion of "family with sequence similarity 104 member A" ( FAM104A) gene at 5-end with EEF1D gene at 3 end. There are no data about the respective chimeric transcript or protein and the role of this genomic alteration is unknown.
Entity name
Neurological and neurodevelopmental disorders
Note
Mutations of EEF1D are involved in neurodevelopmental abnormalities, severe intellectual disability (ID) and microcephaly (McLachlan et al., 2018; Reuter et al., 2017). In particular, some authors identified a pathogenic variant of EEF1DL that could be a candidate for the autosomal recessive ID (ARID) due to its loss of function (Ugur Iseri et al., 2019). In addition, also the interaction between eEF1D and SIAH1 could impact on the initiation of neurodegenerative diseases when eEF1D is over-expressed (Wu et al., 2011).
Entity name
Oesophageal carcinoma
Note
It was detected an EEF1D gene copy number gain in TE8, TE10 and TE11 oesophageal cancer cell lines (http://www.oasis-genomics.org/) and an EEF1D overexpression in oesophageal carcinoma and cardioesophageal carcinoma samples respect noncancerous ones (Veremieva et al., 2011; Ogawa et al., 2004). In addition, it was found a significant correlation between EEF1D overexpression and advanced disease stages and also lymph node metastasis and this correlates with poor prognosis (Ogawa et al., 2004). Some fusion genes and genomic translocation are reported (Babiceanu et al.,2016; https://fusionhub.persistent.co.in/home.html; https://ccsm.uth.edu/FusionGDB/index.html).
Hybrid gene
The t(3;8)(p25;q24) TTLL3/EEF1D, t(8;17)(q24;q21) KRT13/EEF1D, t(8;12)(q24;q13) EEF1D/KRT4 translocations and ZC3H3/EEF1D fusion gene were reported in oesophageal carcinoma (ESCA).
In particular, the t(3;8)(p25;q24) TTLL3/EEF1D brings to the formation of a transcript composed by the exons 1 to 3 of "tubulin tyrosine ligase like 3" ( TTLL3) joined with exons 2 to 7 of EEF1D (http://203.255.191.229:8080/chimerdbv31/chimerseq_link.cdb?gene_pair=TTLL3_EEF1D), while the t(8;8)(q24;q24) ZC3H3/EEF1D brings to the formation of a transcript composed by the exon 1 of "zinc finger CCCH-type containing 3" ( ZC3H3) joined with exons 4 to 7 of EEF1D (http://203.255.191.229:8080/chimerdbv31/chimerseq_link.cdb?gene_pair=ZC3H3_EEF1D). Despite what has just been said, these genomic alterations are still poorly understood.
Entity name
Osteosarcoma
Note
EEF1D may play an important role in osteosarcoma tumorigenesis because it is overexpressed in osteosarcoma tissues samples respect to adjacent non-tumor tissues and this enhances the Akt-mTOR and Akt-Bad signalling pathways. In fact, knockdown of EEF1D in MNNG/HOS and U2OS cells (both osteosarcoma cell lines) shows a slight decrease in the phosphorylation of Akt, MTOR and BAD. In addition, the high expression of EEF1D has a positive correlation with recurrences and its expression levels are higher in patients in advanced Enneking stage than in the early stage ones (Cheng et al., 2018). It was reported the translocation t(3;8)(p25;q24) OGG1/EEF1D (Klijn et al., 2015).
Hybrid gene
The t(3;8)(p25;q24) OGG1/EEF1D was detected in sarcoma ES2-TO cell line (Klijn et al., 2015). This rearrangement is originated by the fusion of "8-oxoguanine DNA glycosylase" ( OGG1) gene at 5-end with EEF1D gene at 3 end. There are no data about the respective chimeric transcript or protein and so this genomic alteration is still poorly understood.
Entity name
Ovarian cancer
Note
It was detected an EEF1D gene copy number gain in COV362, KURAMOCHI, OVCAR4, OVCAR8 and SNU119 ovarian cancer cell lines, in about 26% of ovarian serous cystadenocarcinoma donor samples (http://www.oasis-genomics.org/) and also in ovarian clear cell adenocarcinomas and other ovarian cancer samples (Zhang et al., 2015; Sung et al., 2013). Some fusion genes and genomic translocation are reported (Klijn et al., 2015; https://fusionhub.persistent.co.in/home.html; https://ccsm.uth.edu/FusionGDB/index.html).
Hybrid gene
The EEF1D/ PUF60, EEF1D/ TSNARE1 and SCRIB/EEF1D fusion genes originated by t(8;8)(q24;q24) were found in ovarian serous cystadenocarcinoma (OVSC) samples. In addition, the t(8;14)(q24;q23) HIF1A/EEF1D was reported for ovarian clear cell adenocarcinoma OVTOKO cell line (Klijn et al., 2015). This rearrangement is originated by the fusion of "hypoxia inducible factor 1 subunit alpha" ( HIF1A) gene at 5-end with EEF1D gene at 3 end. The roles of these genomic alterations are still unknown.
Entity name
Pancreatic cancer
Note
EEF1D mRNA is found to be down-regulated in pancreatic cancer tissue samples (Hassan et al., 2018).
Entity name
Parkinsons disease
Note
Some rare mutated variants of eEF1D are considered potential candidates in Parkinsons disease. These mutated variants differ from the amino acid sequence of EEF1D for some amino acids substitutions, i.e. in position 290 (Gly/Arg), 325 (Ala/Thr), 549 (Ala/Val) and 601 (Pro/Ser) (Schulte et al., 2014).
Entity name
Prostate cancer
Note
EEF1D mRNA is found to be up-regulated in prostate cancer tissue samples (Hassan et al., 2018). In addition, it was found the translocation t(8;20)(q24;q13) EEF1D/SDC4 (Wu et al., 2012).
Hybrid gene
The t(8;20)(q24;q13) EEF1D/SDC4 was found in prostate adenocarcinoma (PRAD). This rearrangement is originated by the fusion of EEF1D gene at 5-end with "syndecan 4" ( SDC4) gene at 3 end. There are no data about the respective chimeric transcript or protein and the role of this genomic alteration in prostate cancer is unknown.
Entity name
Thyroid cancer
Note
There are no data about EEF1D expression alterations in thyroid cancers. However, it was reported the EEF1D/TG fusion gene (https://fusionhub.persistent.co.in/home.html; https://ccsm.uth.edu/FusionGDB/index.html).
Hybrid gene
The EEF1D/TG fusion gene was reported in thyroid Carcinoma (THCA). This rearrangement is originated by the fusion of EEF1D gene at 5-end with "thyroglobulin" ( TG) gene at 3 end due to the translocation t(8;8)(q24;q24). There are no data about its chimeric transcript or protein and the role of this genomic alteration is unknown.
Entity name
Uterine cancer
Note
It was detected an EEF1D gene copy number gain in about 14% of uterine carcinosarcoma donor samples (http://www.oasis-genomics.org/). It was found the translocation t(8;17)(q24;q21) EEF1D/KRT14 (Alaei-Mahabadi et al., 2016).
Hybrid gene
The t(8;17)(q24;q21) EEF1D/KRT14 was found in cervical squamous cell carcinoma (CESC). This rearrangement is originated by the fusion of EEF1D gene at 5-end with "keratin 14" ( KRT14) gene at 3 end. There are no data about the respective chimeric transcript or protein and the role of this genomic alteration is unknown.

Article Bibliography

Pubmed IDLast YearTitleAuthors
278567562016Global analysis of somatic structural genomic alterations and their impact on gene expression in diverse human cancers.Alaei-Mahabadi B et al
268375762016Recurrent chimeric fusion RNAs in non-cancer tissues and cells.Babiceanu M et al
82944611994Reconstitution in vitro of the valyl-tRNA synthetase-elongation factor (EF) 1 beta gamma delta complex. Essential roles of the NH2-terminal extension of valyl-tRNA synthetase and of the EF-1 delta subunit in complex formation.Bec G et al
124233342002Regulation of peptide-chain elongation in mammalian cells.Browne GJ et al
254366082014Characterisation of translation elongation factor eEF1B subunit expression in mammalian cells and tissues and co-localisation with eEF1A2.Cao Y et al
295107272018EEF1D overexpression promotes osteosarcoma cell proliferation by facilitating Akt-mTOR and Akt-bad signaling.Cheng DD et al
169685462006Medulloblastoma outcome is adversely associated with overexpression of EEF1D, RPL30, and RPS20 on the long arm of chromosome 8.De Bortoli M et al
229569522012Transcriptome-wide detection of differentially expressed coding and non-coding transcripts and their clinical significance in prostate cancer.Erho N et al
268235602016EEF1D modulates proliferation and epithelial-mesenchymal transition in oral squamous cell carcinoma.Flores IL et al
219365672011Unbiased functional proteomics strategy for protein kinase inhibitor validation and identification of bona fide protein kinase substrates: application to identification of EEF1D as a substrate for CK2.Gyenis L et al
196022322009Identification of potential therapeutic targets in human head & neck squamous cell carcinoma.Han J et al
293422192018The expression profile and prognostic significance of eukaryotic translation elongation factors in different cancers.Hassan MK et al
293379012018Transcriptional-Readthrough RNAs Reflect the Phenomenon of "A Gene Contains Gene(s)" or "Gene(s) within a Gene" in the Human Genome, and Thus Are Not Chimeric RNAs.He Y et al
233219182013A delayed antioxidant response in heat-stressed cells expressing a non-DNA binding HSF1 mutant.Hensen SM et al
127216312003An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene.Hirotsune S et al
79893071994The subunit structure of elongation factor 1 from Artemia. Why two alpha-chains in this complex?Janssen GM et al
162298382005Three-dimensional reconstruction of the valyl-tRNA synthetase/elongation factor-1H complex and localization of the delta subunit.Jiang S et al
117115422002Oncogenic potential of mouse translation elongation factor-1 delta, a novel cadmium-responsive proto-oncogene.Joseph P et al
152243492004Expression profile of eukaryotic translation factors in human cancer tissues and cell lines.Joseph P et al
271122112016Integrating text mining, data mining, and network analysis for identifying genetic breast cancer trends.Jurca G et al
215974682011Transformation of eEF1Bδ into heat-shock response transcription factor by alternative splicing.Kaitsuka T et al
125519732003Conserved protein kinases encoded by herpesviruses and cellular protein kinase cdc2 target the same phosphorylation site in eukaryotic elongation factor 1delta.Kawaguchi Y et al
192429322009Proteomic analysis of multidrug-resistance mechanisms in adriamycin-resistant variants of DLKP, a squamous lung cancer cell line.Keenan J et al
262271782015Recurrent fusion transcripts detected by whole-transcriptome sequencing of 120 primary breast cancer samples.Kim J et al
254856192015A comprehensive transcriptional portrait of human cancer cell lines.Klijn C et al
166244252006eEF1B: At the dawn of the 21st century.Le Sourd F et al
122105012002Blocking the translation elongation factor-1 delta with its antisense mRNA results in a significant reversal of its oncogenic potential.Lei YX et al
263394022015Papillary renal cell carcinoma: a clinicopathological and whole-genome exon sequencing study.Liu K et al
119854942002Mapping the human translation elongation factor eEF1H complex using the yeast two-hybrid system.Mansilla F et al
303709942019The role of translation elongation factor eEF1 subunits in neurodevelopmental disorders.McLachlan F et al
231258412012Characterization of staufen1 ribonucleoproteins by mass spectrometry and biochemical analyses reveal the presence of diverse host proteins associated with human immunodeficiency virus type 1.Milev MP et al
97987841998Multiple phosphorylation sites and quaternary organization of guanine-nucleotide exchange complex of elongation factor-1 (EF-1betagammadelta/ValRS) control the various functions of EF-1alpha.Minella O et al
151993882004Clinical significance of elongation factor-1 delta mRNA expression in oesophageal carcinoma.Ogawa K et al
127735472003Kinectin anchors the translation elongation factor-1 delta to the endoplasmic reticulum.Ong LL et al
297555722018Introducing Potential Key Proteins and Pathways in Human Laryngeal Cancer: A System Biology Approach.Peyvandi H et al
188362332008Proteomics of chondrocytes with special reference to phosphorylation changes of proteins in stretched human chondrosarcoma cells.Piltti J et al
280973212017Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.Reuter MS et al
87439581996Immunofluorescence studies of human fibroblasts demonstrate the presence of the complex of elongation factor-1 beta gamma delta in the endoplasmic reticulum.Sanders J et al
83341681993The human leucine zipper-containing guanine-nucleotide exchange protein elongation factor-1 delta.Sanders J et al
217081172011Expression of endoplasmic reticulum stress proteins is a candidate marker of brain metastasis in both ErbB-2+ and ErbB-2- primary breast tumors.Sanz-Pamplona R et al
242415072014Rare variants in LRRK1 and Parkinson's disease.Schulte EC et al
230046782013Comparative proteomic study for profiling differentially expressed proteins between Chinese left- and right-sided colon cancers.Shen H et al
94071201997Recombinant subunits of mammalian elongation factor 1 expressed in Escherichia coli. Subunit interactions, elongation activity, and phosphorylation by protein kinase CKII.Sheu GT et al
109533162000Enhanced expression of translation factor mRNAs in hepatocellular carcinoma.Shuda M et al
110013222000Identification of novel proteins associated with the development of chemoresistance in malignant melanoma using two-dimensional electrophoresis.Sinha P et al
219584272011Genomic and phenotypic analysis of BRCA2 mutated breast cancers reveals co-occurring changes linked to progression.Stefansson OA et al
237261442013Integrative analysis of copy number alteration and gene expression profiling in ovarian clear cell adenocarcinoma.Sung CO et al
294996552018Identification of novel enriched recurrent chimeric COL7A1-UCN2 in human laryngeal cancer samples using deep sequencing.Tao Y et al
307874222019Biallelic loss of EEF1D function links heat shock response pathway to autosomal recessive intellectual disability.Ugur Iseri SA et al
209646812011Unbalanced expression of the translation complex eEF1 subunits in human cardioesophageal carcinoma.Veremieva M et al
199976362009The role of copy number variation in susceptibility to amyotrophic lateral sclerosis: genome-wide association study and comparison with published loci.Wain LV et al
229273082012Poly-gene fusion transcripts and chromothripsis in prostate cancer.Wu C et al
216339002011Eukaryotic translation elongation factor 1 delta inhibits the ubiquitin ligase activity of SIAH-1.Wu H et al
179978622007BMP-6 promotes E-cadherin expression through repressing deltaEF1 in breast cancer cells.Yang S et al
255005442015The landscape and therapeutic relevance of cancer-associated transcript fusions.Yoshihara K et al
267358892016Identification of ovarian cancer subtype-specific network modules and candidate drivers through an integrative genomics approach.Zhang D et al
186763562008Biological background of pediatric medulloblastoma and ependymoma: a review from a translational research perspective.de Bont JM et al
118238602002Gene expression profiling predicts clinical outcome of breast cancer.van 't Veer LJ et al

Other Information

Locus ID:

NCBI: 1936
MIM: 130592
HGNC: 3211
Ensembl: ENSG00000104529

Variants:

dbSNP: 1936
ClinVar: 1936
TCGA: ENSG00000104529
COSMIC: EEF1D

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000104529ENST00000317198P29692
ENSG00000104529ENST00000395119P29692
ENSG00000104529ENST00000419152P29692
ENSG00000104529ENST00000423316P29692
ENSG00000104529ENST00000442189P29692
ENSG00000104529ENST00000524397E9PMW7
ENSG00000104529ENST00000524624P29692
ENSG00000104529ENST00000524883E9PN56
ENSG00000104529ENST00000524900E9PLS6
ENSG00000104529ENST00000525223E9PKK3
ENSG00000104529ENST00000525261E9PLT8
ENSG00000104529ENST00000526133E9PJ84
ENSG00000104529ENST00000526135E9PI93
ENSG00000104529ENST00000526340E9PK72
ENSG00000104529ENST00000526710E9PQR8
ENSG00000104529ENST00000526838P29692
ENSG00000104529ENST00000528303E9PLL8
ENSG00000104529ENST00000528382E9PQC9
ENSG00000104529ENST00000528519E9PPY1
ENSG00000104529ENST00000528610P29692
ENSG00000104529ENST00000529007E9PMW7
ENSG00000104529ENST00000529272P29692
ENSG00000104529ENST00000529516E9PK06
ENSG00000104529ENST00000529576H0YE58
ENSG00000104529ENST00000529832E9PNC8
ENSG00000104529ENST00000530109H0YE72
ENSG00000104529ENST00000530191E9PI39
ENSG00000104529ENST00000530306E9PKH7
ENSG00000104529ENST00000530445E9PPR1
ENSG00000104529ENST00000530545E9PLA1
ENSG00000104529ENST00000530616H0YCK7
ENSG00000104529ENST00000531218E9PQ49
ENSG00000104529ENST00000531281E9PRL0
ENSG00000104529ENST00000531621E9PQZ1
ENSG00000104529ENST00000531670E9PJV8
ENSG00000104529ENST00000531931E9PNW6
ENSG00000104529ENST00000531953E9PIP5
ENSG00000104529ENST00000532400E9PJD0
ENSG00000104529ENST00000532543E9PKK3
ENSG00000104529ENST00000532596E9PN71
ENSG00000104529ENST00000532741E9PRY8
ENSG00000104529ENST00000533204E9PI39
ENSG00000104529ENST00000533494E9PL12
ENSG00000104529ENST00000533749E9PIZ1
ENSG00000104529ENST00000533833E9PN91
ENSG00000104529ENST00000534377E9PL71
ENSG00000104529ENST00000534380E9PK01
ENSG00000104529ENST00000534475E9PL21
ENSG00000104529ENST00000534804E9PM66
ENSG00000104529ENST00000618139A0A087X1X7

Expression (GTEx)

0
50
100
150
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Herpes simplex infectionKEGGko05168
Herpes simplex infectionKEGGhsa05168
Metabolism of proteinsREACTOMER-HSA-392499
TranslationREACTOMER-HSA-72766
Eukaryotic Translation ElongationREACTOMER-HSA-156842
Gene ExpressionREACTOMER-HSA-74160

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

References

Pubmed IDYearTitleCitations
383329122023Autoantibodies against eukaryotic translation elongation factor 1 delta in two patients with autoimmune cerebellar ataxia.0
383329122023Autoantibodies against eukaryotic translation elongation factor 1 delta in two patients with autoimmune cerebellar ataxia.0
330295232020EEF1D Promotes Glioma Proliferation, Migration, and Invasion through EMT and PI3K/Akt Pathway.10
330874622020Eukaryotic Translation Elongation Factor 1 Delta Inhibits the Nuclear Import of the Nucleoprotein and PA-PB1 Heterodimer of Influenza A Virus.16
330295232020EEF1D Promotes Glioma Proliferation, Migration, and Invasion through EMT and PI3K/Akt Pathway.10
330874622020Eukaryotic Translation Elongation Factor 1 Delta Inhibits the Nuclear Import of the Nucleoprotein and PA-PB1 Heterodimer of Influenza A Virus.16
307874222019Biallelic loss of EEF1D function links heat shock response pathway to autosomal recessive intellectual disability.6
307874222019Biallelic loss of EEF1D function links heat shock response pathway to autosomal recessive intellectual disability.6
295107272018EEF1D overexpression promotes osteosarcoma cell proliferation by facilitating Akt-mTOR and Akt-bad signaling.19
295107272018EEF1D overexpression promotes osteosarcoma cell proliferation by facilitating Akt-mTOR and Akt-bad signaling.19
268235602016EEF1D modulates proliferation and epithelial-mesenchymal transition in oral squamous cell carcinoma.19
268235602016EEF1D modulates proliferation and epithelial-mesenchymal transition in oral squamous cell carcinoma.19
216339002011Eukaryotic translation elongation factor 1 delta inhibits the ubiquitin ligase activity of SIAH-1.9
219365672011Unbiased functional proteomics strategy for protein kinase inhibitor validation and identification of bona fide protein kinase substrates: application to identification of EEF1D as a substrate for CK2.18
216339002011Eukaryotic translation elongation factor 1 delta inhibits the ubiquitin ligase activity of SIAH-1.9

Citation

Luigi Cristiano

EEF1D (eukaryotic translation elongation factor 1 delta)

Atlas Genet Cytogenet Oncol Haematol. 2019-05-01

Online version: http://atlasgeneticsoncology.org/gene/43240/eef1d-%28eukaryotic-translation-elongation-factor-1-delta%29