EIF2S1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1KL9, 1Q8K
Identifiers
Aliases	EIF2S1, EIF-2, EIF-2A, EIF-2alpha, EIF2, EIF2A, eukaryotic translation initiation factor 2 subunit alpha
External IDs	OMIM: 603907 MGI: 95299 HomoloGene: 3020 GeneCards: EIF2S1
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q23.3 Start 67,360,328 bp[1] End 67,386,516 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12|12 C3 Start 78,908,593 bp[2] End 78,933,784 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in islet of Langerhans monocyte gastrocnemius muscle ganglionic eminence stromal cell of endometrium right ventricle appendix body of pancreas rectum popliteal artery Top expressed in morula corneal stroma yolk sac spermatocyte lens spermatid neural tube superior surface of tongue plantaris muscle extensor digitorum longus muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function translation initiation factor activity ribosome binding protein binding nucleic acid binding RNA binding Cellular component cytoplasm eukaryotic 48S preinitiation complex polysome cytosol ribosome membrane multi-eIF complex eukaryotic translation initiation factor 2B complex glial limiting end-foot translation initiation ternary complex cytoplasmic stress granule extracellular exosome nucleus eukaryotic translation initiation factor 2 complex synapse Biological process cellular response to heat positive regulation of type B pancreatic cell apoptotic process negative regulation of translational initiation in response to stress cellular response to UV cellular response to amino acid starvation human ageing response to endoplasmic reticulum stress PERK-mediated unfolded protein response response to manganese-induced endoplasmic reticulum stress transmembrane transport translational initiation protein autophosphorylation regulation of translation regulation of translational initiation in response to stress negative regulation of guanyl-nucleotide exchange factor activity positive regulation of neuron death protein biosynthesis stress granule assembly cellular response to oxidative stress Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1965 13665 Ensembl ENSG00000134001 ENSMUSG00000021116 UniProt P05198 Q6ZWX6 RefSeq (mRNA) NM_004094 NM_026114 RefSeq (protein) NP_004085 NP_080390 Location (UCSC) Chr 14: 67.36 – 67.39 Mb Chr 12: 78.91 – 78.93 Mb PubMed search [3] [4]
Wikidata
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Eukaryotic translation initiation factor 2 subunit 1 (eIF2α) is a protein that in humans is encoded by the EIF2S1 gene.^[5][6]

Function

The protein encoded by this gene is the alpha (α) subunit of the translation initiation factor eIF2 protein complex which catalyzes an early regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA (Met-tRNA_i^Met) to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, eIF2, and GTP. eIF2 is composed of 3 nonidentical subunits, alpha (α, 36 kD, this article), beta (β, 38 kD), and gamma (γ, 52 kD). The rate of formation of the ternary complex is modulated by the phosphorylation state of eIF2α.^[6] Phosphorylation of eIF2α by EIF-2 kinases plays a key role in regulating the integrated stress response.^[7]

Clinical significance

After reperfusion following brain ischemia, there is inhibition of neuron protein synthesis due to phosphorylation of eIF2α. There is colocalization between phosphorylated eIF2α and cytosolic cytochrome c, which is released from mitochondria in apoptosis. Phosphorylated Eif2-alpha appeared before cytochrome c release, suggesting that phosphorylation of eIF2α triggers cytochrome c release during apoptotic cell death.^[8]

Mice heterozygous for the S51A mutation become obese and diabetic on a high-fat diet. Glucose intolerance resulted from reduced insulin secretion, defective transport of proinsulin, and a reduced number of insulin granules in beta cells. Hence proper functioning of eIF2α appears essential for preventing diet-induced type II diabetes.^[9]

Dephosphorylation inhibitors

Salubrinal is a selective inhibitor of enzymes that dephosphorylate eIF2α.^[10] Salubrinal also blocks eIF2α dephosphorylation by a herpes simplex virus protein and inhibits viral replication. eIF2α phosphorylation is cytoprotective during endoplasmic reticulum stress.^[11][12]