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eIF2-alpha a translation initiation factor 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 preinitiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B. Phosphorylated by at least 4 kinases: PERK, GCN2, HRI and PKR. Phosphorylation stabilizes the eIF-2/GDP/eIF-2B 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. Upregulated in some thyroid cancers and bronchiolo-alveolar adenocarcinomas; aberrant phosphorylation correlates with Alzheimer disease and Epstein-Barr virus infections. Note: This description may include information from UniProtKB.
Protein type: RNA-binding; Translation; Translation initiation
Chromosomal Location of Human Ortholog: 14q23.3
Cellular Component: cytosol; eukaryotic translation initiation factor 2 complex; eukaryotic translation initiation factor 2B complex; extracellular exosome; membrane; nucleus; polysome; ribosome; stress granule; translation initiation ternary complex
Molecular Function: protein binding; ribosome binding; RNA binding; translation initiation factor activity
Biological Process: aging; cellular response to amino acid starvation; cellular response to heat; cellular response to UV; negative regulation of guanyl-nucleotide exchange factor activity; negative regulation of translational initiation in response to stress; PERK-mediated unfolded protein response; positive regulation of neuron death; positive regulation of type B pancreatic cell apoptotic process; protein autophosphorylation; response to manganese-induced endoplasmic reticulum stress; translational initiation; transmembrane transport
Reference #:  P05198 (UniProtKB)
Alt. Names/Synonyms: EIF-2; eIF-2-alpha; eIF-2A; eIF-2alpha; EIF2; EIF2A; EIF2S1; Eukaryotic translation initiation factor 2 subunit 1; Eukaryotic translation initiation factor 2 subunit alpha; eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa; IF2A
Gene Symbols: EIF2S1
Molecular weight: 36,112 Da
Basal Isoelectric point: 5.02  Predict pI for various phosphorylation states
CST Pathways:  Translation: eIF2  |  Translational Control
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