Eukaryotic translation initiation factor 2 subunit 1 (Eukaryotic translation initiation factor 2 subunit alpha) (eIF-2-alpha) (eIF-2A) (eIF-2alpha)
1_MPGLS 6_ CRFYQ 11_ HKFPE 16_ VEDVV 21_ MVNVR 26_ SIAEM 31_ GAYVS 36_ LLEYN 41_ NIEGM 46_ ILLSE 51_ LSRRR 56_ IRSIN 61_ KLIRI 66_ GRNEC 71_ VVVIR 76_ VDKEK 81_ GYIDL 86_ SKRRV 91_ SPEEA 96_ IKCED 101_ KFTKS 106_ KTVYS 111_ ILRHV 116_ AEVLE 121_ YTKDE 126_ QLESL 131_ FQRTA 136_ WVFDD 141_ KYKRP 146_ GYGAY 151_ DAFKH 156_ AVSDP 161_ SILDS 166_ LDLNE 171_ DEREV 176_ LINNI 181_ NRRLT 186_ PQAVK 191_ IRADI 196_ EVACY 201_ GYEGI 206_ DAVKE 211_ ALRAG 216_ LNCST 221_ ENMPI 226_ KINLI 231_ APPRY 236_ VMTTT 241_ TLERT 246_ EGLSV 251_ LSQAM 256_ AVIKE 261_ KIEEK 266_ RGVFN 271_ VQMEP 276_ KVVTD 281_ TDETE 286_ LARQM 291_ ERLER 296_ ENAEV 301_ DGDDD 306_AEEME
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 (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)