Eukaryotic translation initiation factor 2 subunit 1 (EIF2S1)
The protein contains 315 amino acids for an estimated molecular weight of 36112 Da.
Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA (PubMed:16289705). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex (PubMed:16289705). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex (PubMed:16289705). In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B (PubMed:16289705). EIF2S1/eIF-2-alpha is a key component of the integrated stress response (ISR), required for adaptation to various stress: phosphorylation by metabolic-stress sensing protein kinases (EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2) in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to an attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (PubMed:19131336, PubMed:33384352). (updated: June 2, 2021)
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.
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Biological Process
Aging
Cellular protein metabolic process
Cellular response to amino acid starvation
Cellular response to heat
Cellular response to oxidative stress
Cellular response to UV
Endoplasmic reticulum unfolded protein response
Gene expression
Negative regulation of guanyl-nucleotide exchange factor activity
Negative regulation of translational initiation in response to stress
Obsolete activation of signaling protein activity involved in unfolded protein response
PERK-mediated unfolded protein response
Positive regulation of neuron death
Positive regulation of type B pancreatic cell apoptotic process
Protein autophosphorylation
Regulation of translational initiation in response to stress
Response to endoplasmic reticulum stress
Response to manganese-induced endoplasmic reticulum stress
Stress granule assembly
Translation
Translational initiation
Transmembrane transport
Cellular Component
Cytoplasmic stress granule
Cytosol
Eukaryotic 48S preinitiation complex
Eukaryotic translation initiation factor 2 complex
Eukaryotic translation initiation factor 2B complex
Extracellular exosome
Glial limiting end-foot
Membrane
Multi-eIF complex
Nucleus
Polysome
Ribosome
Synapse
Translation initiation ternary complex
Molecular Function
Poly(A) RNA binding
Ribosome binding
RNA binding
Translation initiation factor activity
The reference OMIM entry for this protein is 603907
Eukaryotic translation initiation factor 2, subunit 1; eif2s1
Eukaryotic translation initiation factor 2-alpha
Eif2-alpha
DESCRIPTION
The translation initiation factor EIF2 catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, EIF2, and GTP. EIF2 is composed of 3 nonidentical subunits, the 36-kD EIF2-alpha subunit (EIF2S1), the 38-kD EIF2-beta subunit (EIF2S2; 603908), and the 52-kD EIF2-gamma subunit (EIF2S3; 300161). The rate of formation of the ternary complex is modulated by the phosphorylation state of EIF2-alpha (Ernst et al., 1987).CLONING
By screening a rat brain expression library with antibodies against human EIF2S1, which they called EIF2-alpha, Ernst et al. (1987) isolated cDNAs encoding rat Eif2-alpha. They used a rat cDNA to screen a human fibroblast library and recovered a human EIF2-alpha cDNA. The predicted 315-amino acid human and rat proteins differ at only 3 residues and are likely processed posttranslationally by removal of their N-terminal methionines. Northern blot analysis detected a 1.6-kb EIF2-alpha mRNA in HeLa cells.NOMENCLATURE
EIF2-alpha should not be confused with EIF2A (609234), a distinct translation initiation factor.GENE FUNCTION
Ernst et al. (1987) stated that protein synthesis is inhibited due to phosphorylation of Eif2-alpha in hemin-deprived rabbit reticulocyte lysates. HeLa cells subjected to heat shock, serum deprivation, or interferon treatment followed by virus infection also show a correlation between EIF2-alpha phosphorylation and translational repression. EIF2 must associate with EIF2B (see 606686) to function catalytically, and phosphorylation of EIF2-alpha results in formation of irreversible inactive complexes with EIF2B, thereby preventing mRNA translation. Ernst et al. (1987) found that the decrease of EIF2-alpha protein synthesis in serum-depleted HeLa cells appeared to be due to specific modulation of the rate of translation initiation of existing EIF2-alpha mRNA. Using site-directed mutagenesis, in vitro translation, and 2-dimensional gel electrophoresis, Pathak et al. (1988) identified ser51 in the mature human EIF2-alpha protein as the sole site of phosphorylation leading to repression of protein synthesis. Jacob et al. (1989) found that the alpha-Pal (NRF1; 600879) transcription factor bound to 2 palindromic sites within the EIF2-alpha promoter and was essential for transcription of the EIF2-alpha gene. Noguchi et al. (1994) identified an EIF2-alpha antisense transcript in vivo and found that it appeared to modulate EIF2-alpha gene expression. Upon brain reperfusion following ischemia, there is widespread inhibition of neuronal protein synthesis due to phosphorylation of Eif2-alpha, which persists in vulnerable neurons destined to undergo apoptosis. Page et al. (2003) examined rat CA1 pyramidal neurons at 4 hours of reperfusion following 10-minute cardiac arrest and found complete colocalization between phosphorylated Eif2-alpha and cytosolic cytochrome c (see 516030), which is released from mitochondria early in apoptosis. Phosphorylated Eif2-alpha appeared before cytochrome c release, suggesting that phosphorylation of Eif2-alpha is upstream of cytochrome c release during apoptotic cell death. Blais et al. (2004) determined that EIF2-alpha, PERK (EIF2AK3; 604032), ATF4 (604064), and GADD34 (PPP1R15A; 611048) are involved in an integrated adaptive response to hypoxic stress in HeLa cells. GTP hydrolysis by EIF2 is a ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603907 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed