Eukaryotic initiation factor 4A-II (EIF4A2)
The protein contains 407 amino acids for an estimated molecular weight of 46402 Da.
ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon. (updated: March 4, 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.
- 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.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs11538616 | |
| a breast cancer sample; somatic mutation |
Biological Process
Cellular protein metabolic process
Cellular response to leukemia inhibitory factor
Cytokine-mediated signaling pathway
Cytoplasmic translational initiation
Gene expression
Negative regulation of RNA-directed 5'-3' RNA polymerase activity
Nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
Nuclear-transcribed mRNA poly(A) tail shortening
Regulation of translational initiation
RNA secondary structure unwinding
Translation
Translational initiation
Viral process
The reference OMIM entry for this protein is 601102
Eukaryotic translation initiation factor 4a, isoform 2; eif4a2
Ddx2b
Eukaryotic initiation factor 4A plays an important role in the binding of mRNA to the 43S preinitiation complex when protein synthesis begins. Two highly homologous forms of functional EIF4A genes, Eif4a1 (602641) and Eif4a2, have been isolated in mice (Nielsen and Trachsel, 1988); yeast cells also possess 2 EIF4A genes, TIF1 and TIF2 (601993). The murine Eif4a and yeast TIF genes appear to belong to a DEAD-box gene family, whose members exhibit extensive amino acid similarity and contain the asp-glu-ala-asp (DEAD) sequence. DEAD-box genes have been identified in species ranging from E-coli to humans. Their function appears to be related to transcriptional/translational regulation.
CLONING
Sudo et al. (1995) isolated human cDNA highly homologous to murine Eif4a2, which encodes one of the protein-synthesis initiation factors involved in the binding of mRNA to the ribosome. The human homolog was expressed in all normal tissues examined, but in variable amounts, being highly expressed in skeletal muscle and ovary, and less abundantly in liver, kidney, and pancreas.GENE FUNCTION
Meijer et al. (2013) demonstrated that translational inhibition is the primary event required for mRNA degradation. Translational inhibition depends on miRNAs impairing the function of the eIF4F initiation complex. Meijer et al. (2013) defined the RNA helicase eIF4A2 as the key factor of eIF4F through which microRNAs function. They uncovered a correlation between the presence of miRNA target sites in the 3-prime untranslated region (UTR) of mRNAs and secondary structure in the 5-prime UTR, and showed that mRNAs with unstructured 5-prime UTRs are refractory to miRNA repression. Meijer et al. (2013) concluded that their data supported a linear model for miRNA-mediated gene regulation in which translational repression via eIF4A2 is required first, followed by mRNA destabilization.MAPPING
Nielsen et al. (1993) mapped the mouse Eif4a2 gene to chromosome 16. By fluorescence in situ hybridization, Sudo et al. (1995) mapped the EIF4A2 gene to 18p11.2. The International Radiation Hybrid Mapping Consortium mapped the EIF4A2 gene to chromosome 3 (TMAP WI-30529) in a region of conserved synteny with mouse chromosome 16. ... More on the omim web site
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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601102 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed