Recombinant Human EIF2S1 Protein Standard (His tag)

Specifications

Form

Liquid

General info

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 (PubMed : 16289705, PubMed : 38340717). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex (43S PIC) (PubMed : 16289705). 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 (PubMed : 16289705). 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 (PubMed : 16289705). 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 (PubMed : 19131336, PubMed : 33384352, PubMed : 38340717). 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 (PubMed : 38340717).

Sequence similarities

Belongs to the eIF-2-alpha family.

Post-translational modifications

Phosphorylation at Ser-49 and Ser-52 stabilizes the eIF-2/GDP/eIF2B complex and prevents GDP/GTP exchange reaction, thus impairing the recycling of eIF-2 between successive rounds of initiation and leading to global inhibition of translation, while concomitantly initiating the preferential translation of integrated stress response (ISR)-specific mRNAs (PubMed:10026192, PubMed:15207627, PubMed:18032499, PubMed:19131336, PubMed:31048492). Substrate for at least 4 kinases: EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2 (PubMed:15489334, PubMed:38340717). Phosphorylation on Ser-52 by the EIF2AK4/GCN2 protein kinase occurs in response to amino acid starvation and UV irradiation (By similarity). Phosphorylation at Ser-52 by the EIF2AK3/PERK protein kinase occurs in response to the unfolded protein response (PubMed:10026192). Phosphorylation at Ser-52 by EIF2AK1/HRI in response to mitochondrial damage promotes relocalization to the mitochondrial surface (PubMed:38340717).. (Microbial infection) Phosphorylation by vaccinia virus protein E3 and rotavirus A stabilizes the eIF-2/GDP/eIF2B complex and prevents GDP/GTP exchange reaction, thus impairing the recycling of eIF-2 between successive rounds of initiation and leading to global inhibition of translation.