Eukaryotic initiation factor 4A-III (EIF4A3)
The protein contains 411 amino acids for an estimated molecular weight of 46871 Da.
ATP-dependent RNA helicase (PubMed:16170325). Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:22961380, PubMed:28502770, PubMed:28076346, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs (PubMed:16209946, PubMed:16170325, PubMed:16314458, PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275). The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Its RNA-dependent ATPase and RNA-helicase activities are induced by CASC3, but abolished in presence of the MAGOH-RBM8A heterodimer, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The inhibition of ATPase activity by the MAGOH-RBM8A heterodimer increases the RNA-binding affinity of the EJC. Involved in translational enhancement of spliced mRNAs after formation of the 80S ribosome complex. Binds spliced mRNA in sequence-indepe (updated: May 8, 2019)
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.
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.
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| Variant | Description |
|---|---|
| RCPS |
Biological Process
Associative learning
Cellular response to brain-derived neurotrophic factor stimulus
Cellular response to selenite ion
Cytokine-mediated signaling pathway
Embryonic cranial skeleton morphogenesis
Exploration behavior
Gene expression
MRNA 3'-end processing
MRNA export from nucleus
MRNA splicing, via spliceosome
MRNA transport
Negative regulation of excitatory postsynaptic potential
Negative regulation of selenocysteine incorporation
Negative regulation of selenocysteine insertion sequence binding
Negative regulation of translation
Nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
Nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
Nuclear-transcribed mRNA poly(A) tail shortening
Positive regulation of translation
Regulation of translation at postsynapse, modulating synaptic transmission
Response to organic cyclic compound
RNA export from nucleus
RNA secondary structure unwinding
RNA splicing
RRNA processing
Termination of RNA polymerase II transcription
The reference OMIM entry for this protein is 268305
Robin sequence with cleft mandible and limb anomalies
Richieri-costa-pereira syndrome; rcps
A number sign (#) is used with this entry because of evidence that Robin sequence with cleft mandible and limb anomalies is caused by homozygous or compound heterozygous mutation in the EIF4A3 gene (608546) on chromosome 17q25.
DESCRIPTION
Patients with Richieri-Costa-Pereira syndrome display a pattern of anomalies consisting of microstomia, micrognathia, abnormal fusion of the mandible, cleft palate/Robin sequence, absence of lower central incisors, minor ear anomalies, hypoplastic first ray, abnormal tibiae, hypoplastic halluces, and clubfeet. Learning disability is also a common finding (summary by Favaro et al., 2011).CLINICAL FEATURES
Richieri-Costa and Pereira (1992) described a seemingly distinct entity in 5 unrelated Brazilian patients. The features were short stature, Robin sequence, cleft mandible, and limb defects. The ears were low set and prominent. Retromicrognathia, microstomia, highly arched palate, and cleft lower alveolar ridge was accompanied by hypoplastic mandible and cleft through the midline with absence of the lower incisors by x-ray. The thumbs were hypoplastic, as was the distal part of the tibias with proximal and lateral displacement of the fibulas and clubfoot. Females had apparently normal intellect; the oldest was 6 years at the time of the report. Affected males were either stillborn or died within 1 week of birth; more severe defects, including apodia, were noted in 1. Richieri-Costa and Pereira (1993) reported 2 male patients, aged 1 year and 13 years, from 2 unrelated Brazilian families, who were no more severely affected than previously reported females. Since 6 of the 7 reported families came from the same area of Sao Paulo, Richieri-Costa and Pereira (1993) thought it likely that they had a common ancestor. Tabith and Bento-Goncalves (1996) examined 5 patients with the Richieri-Costa-Pereira syndrome, 3 of whom had previously been reported by Richieri-Costa and Pereira (1992, 1993). All patients had the same laryngeal anomalies with variable severity: small, round larynx, absent or hypoplastic epiglottis, hypertrophic aryepiglottic folds, and a fold in the posterior part of the larynx above the level of the glottis. During emission of sounds there was a medialization of the aryepiglottic folds, probably a protection mechanism of the inferior airways upon swallowing. Tabith and Bento-Goncalves (1996) concluded that these anatomic and functional abnormalities cause the voice disorder (marked hoarseness and breathiness) characteristic of the syndrome. Tabith and Bento-Goncalves (2003) examined 2 additional patients with this syndrome and found the same laryngeal alterations and voice characteristics. Walter-Nicolet et al. (1999) described this syndrome in a newborn French boy who probably represented the first non-Brazilian case. Born to consanguineous parents, he showed cleft mandible, pre/postaxial hand anomalies, and clubfoot. Ferreira de Lima et al. (2003) studied 15 families using identity by descent as a hypothesis to attempt gene localization. Fourteen families were Brazilian, suggesting a founder effect. They examined through linkage analysis 497 polymorphic markers and also performed direct sequencing of exons for 10 candidate genes selected on the basis of their expression in the developing mandible and limb. No evidence for allele sharing at any locus tested or mutations in candidate genes were found. Golbert et al. (2007) reported another Brazilian female with this di ... More on the omim web site
May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
April 12, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 268305 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed