EIF2S1
EIF2S1 (eukaryotic translation initiation factor 2 subunit 1, also known as eIF2-alpha, EIF-2alpha, EIF2A and EIF2) is the alpha subunit of the eIF2 complex, which delivers initiator tRNA to the ribosome. Its phosphorylation makes it a central regulator of the integrated stress response. Browse Assay Genie's current range of EIF2S1 research reagents below, or read on for the biology behind the target.
EIF2S1 is a member of the eIF2 complex, which acts in the early steps of protein synthesis. eIF2 forms a ternary complex with GTP and initiator methionyl-tRNA, and this complex binds a 40S ribosomal subunit. mRNA binding then yields the 43S pre-initiation complex. Before the 60S subunit joins to form the 80S initiation complex, the GTP bound to eIF2 is hydrolysed and an eIF2-GDP binary complex is released. For eIF2 to recycle and catalyse another round of initiation, its GDP must be exchanged for GTP in a reaction catalysed by eIF2B.
The eIF2 complex has three non-identical subunits: the alpha subunit encoded by the EIF2S1 gene, the beta subunit (EIF2S2) and the gamma subunit (EIF2S3). The rate of ternary complex formation is modulated by the phosphorylation state of eIF2-alpha. The protein belongs to the eIF-2-alpha family and is found in the cytosol, in stress granules and in mitochondria. The mouse and rat orthologues are both named Eif2s1.
EIF2S1 is a key component of the integrated stress response (ISR). Metabolic-stress sensing kinases, namely EIF2AK1 (HRI), EIF2AK2 (PKR), EIF2AK3 (PERK) and EIF2AK4 (GCN2), phosphorylate eIF2-alpha under stress. This turns it into a global inhibitor of protein synthesis and attenuates cap-dependent translation. At the same time it favours translation of ISR-specific mRNAs, including those for the transcriptional activators ATF4 and QRICH1, which then drive reprogramming of gene expression. eIF2-alpha also activates mitophagy after mitochondrial damage: phosphorylation by HRI promotes its relocalisation to the mitochondrial surface and triggers PRKN-independent mitophagy. Researchers studying the EIF2S1 gene and eIF2-alpha therefore often work on translational control and stress adaptation.
eIF2-alpha is part of the eIF2 complex that forms the ternary complex with GTP and initiator tRNA at the start of protein synthesis.
Phosphorylation of EIF2S1 by HRI, PKR, PERK and GCN2 attenuates cap-dependent translation and promotes translation of ATF4 and QRICH1.
EIF2S1 activates PRKN-independent mitophagy after mitochondrial damage, following phosphorylation by EIF2AK1/HRI and relocalisation to the mitochondrial surface.
EIF2S1 localises to stress granules in the cytoplasm, linking translational arrest to the cellular response to stress.
EIF2S1 is the alpha subunit of eIF2, which forms a ternary complex with GTP and initiator tRNA to start translation. When phosphorylated by stress kinases, it inhibits global protein synthesis while promoting translation of ISR mRNAs such as ATF4 and QRICH1.
EIF2S1 is also called eIF2-alpha, EIF-2alpha, EIF2A and EIF2. Earlier names include eukaryotic translation initiation factor 2, subunit 1 (alpha, 35kD). Its UniProt name is eukaryotic translation initiation factor 2 subunit 1. Note that EIF2A is also used as a separate gene symbol.
Yes. Mouse and rat both carry an orthologous gene named Eif2s1. The protein belongs to the eIF-2-alpha family. Check the datasheet of any product for its validated reactivity.
Stress-responsive eIF2 kinases, eIF2B, and other translation initiation factors with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P05198; product specifications from Assay Genie datasheets.