Elongation factor 2 (EEF2)
The protein contains 858 amino acids for an estimated molecular weight of 95338 Da.
Catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| SCA26 |
Biological Process
Aging
Cellular protein metabolic process
Cellular response to brain-derived neurotrophic factor stimulus
Gene expression
Glial cell proliferation
Hematopoietic progenitor cell differentiation
Neutrophil degranulation
Pathogenesis
Peptidyl-diphthamide biosynthetic process from peptidyl-histidine
Positive regulation of cytoplasmic translation
Positive regulation of translation
Post-translational protein modification
Protein methylation
Response to drug
Response to endoplasmic reticulum stress
Response to estradiol
Response to ethanol
Response to folic acid
Response to hydrogen peroxide
Response to ischemia
Skeletal muscle cell differentiation
Skeletal muscle contraction
Translation
Translational elongation
Cellular Component
Aggresome
Cytoplasm
Cytosol
Extracellular exosome
Extracellular matrix
Extracellular region
Ficolin-1-rich granule lumen
Intracellular ribonucleoprotein complex
Membrane
Membrane raft
Nucleus
Plasma membrane
Polysomal ribosome
Polysome
Ribonucleoprotein complex
Secretory granule lumen
Synapse
The reference OMIM entry for this protein is 130610
Eukaryotic translation elongation factor 2; eef2
Elongation factor 2; ef2
Polypeptidyl-trna translocase
DESCRIPTION
The EEF2 gene encodes eukaryotic translation elongation factor-2, which is required for the translocation step in protein synthesis, where peptidyl-tRNA is moved to the next codon on mRNA from the acceptor site on the ribosome at the expense of the energy provided by hydrolysis of GTP bound to EF2 (summary by Kaneda et al., 1984 and Hekman et al., 2012).CLONING
Rapp et al. (1989) reported the complete sequence of the predicted 858-amino acid EF2 protein. Sequence comparisons revealed that the hamster, rat, and human EF2 protein sequences differ in only 8 positions.GENE FUNCTION
Diphtheria toxin and Pseudomonas exotoxin A (PA toxin) inhibit protein synthesis by catalyzing covalent binding of the ADP-ribose moiety of NAD to elongation factor-2 (EF2). Class I diphtheria toxin resistance (sensitivity) is related to binding of the toxin, a function coded by chromosome 5. Class II resistance is due to a defect in protein synthesis such that EF2 is not ADP-ribosylated by diphtheria toxin or PA toxin. In one subclass this is due to a mutation in the structural gene for EF2; in a second subclass it is due to mutation in a gene for posttranslational modification of EF2 (Kaneda et al., 1984). Davydova et al. (2014) found that FAM86A (EEF2KMT; 615263) catalyzed trimethylation of EEF2 on lys525 (K525), which lies in domain III on the outer surface of a highly conserved alpha helix.MAPPING
Kaneda et al. (1984) isolated cells with PA toxin resistance of the first class II type from primary cultures from human embryos. By analysis of hybrid cells constructed from these cells and mouse L cells, they showed that chromosome 19 carries the gene for the resistance, i.e., the EF2 structural locus. By analysis of human-mouse hybrid cells, Kaneda et al. (1987) narrowed the assignment of EF2 to chromosome 19pter-q12.MOLECULAR GENETICS
In affected members of a family of Norwegian origin with autosomal dominant late-onset spinocerebellar ataxia-26 (SCA26; 609306), previously reported by Yu et al. (2005), Hekman et al. (2012) identified a heterozygous mutation in the EEF2 gene (P596H; 130610.0001). Detailed studies of the equivalent mutation in yeast (P580Y) showed that it caused impaired translocation with an increased rate of -1 programmed ribosomal frameshift read-through during translation. Yeast carrying this mutation also showed greater susceptibility to proteostatic disruption, as evidenced by a more robust activation of a reporter gene driven by unfolded protein response activation upon challenge. The results suggested that the mutation disrupted the normal mechanical processes involved in translocation, and indicated that proteostatic disruption can cause a neurodegenerative disease. ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 130610 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed