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Eukaryotic translation initiation factor 2 subunit 1

Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA^1,2. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex (43S PIC)³. 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 complex⁴. 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 eIF2B⁵. 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^6,7,8. 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 mitophagy⁹.

AlphaFold DB , UniProt , Accession P05198, Species HUMAN (Homo sapiens, Human), Gene EIF2S1, Length 315 aa.