| Function | Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex (43S PIC). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF2B. EIF2S1/eIF2-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/eIF2-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. EIF2S1/eIF2-alpha also acts as an activator of mitophagy in response to mitochondrial damage: phosphorylation by EIF2AK1/HRI promotes relocalization to the mitochondrial surface, thereby triggering PRKN-independent mitophagy. |
| Protein Name | Eukaryotic Translation Initiation Factor 2 Subunit 1Eukaryotic Translation Initiation Factor 2 Subunit AlphaEif-2-AlphaEif-2aEif-2alphaEif2-Alpha |
| Database Links | Reactome: R-HSA-156827Reactome: R-HSA-381042Reactome: R-HSA-382556Reactome: R-HSA-72649Reactome: R-HSA-72695Reactome: R-HSA-72702Reactome: R-HSA-72706Reactome: R-HSA-72731Reactome: R-HSA-9633012Reactome: R-HSA-9648895Reactome: R-HSA-9833482Reactome: R-HSA-9840373 |
| Cellular Localisation | CytoplasmStress GranuleCytosolMitochondrionColocalizes With Nanos3 In The Stress GranulesRelocalizes To The Surface Of Mitochondria In Response To Mitochondrial Damage And Phosphorylation By Eif2ak1/Hri |
| Alternative Protein Names | Eukaryotic Translation Initiation Factor 2 Subunit 1 proteinEukaryotic Translation Initiation Factor 2 Subunit Alpha proteinEif-2-Alpha proteinEif-2a proteinEif-2alpha proteinEif2-Alpha proteinEIF2S1 proteinEIF2A protein |
Information sourced from Uniprot.org
