Protein-coding gene in the species Homo sapiens
Not to be confused with
EIF2A .
Eukaryotic translation initiation factor 2 subunit 1 (eIF2α) is aprotein that in humans is encoded by theEIF2S1 gene .[ 5] [ 6]
Theprotein encoded by this gene is the alpha (α) subunit of thetranslation initiation factor eIF2 protein complex which catalyzes an early regulated step ofprotein synthesis initiation, promoting the binding of the initiator tRNA (Met-tRNAi Met ) to40S ribosomal subunits. Binding occurs as a ternary complex ofmethionyl -tRNA ,eIF2 , andGTP . eIF2 is composed of 3 nonidentical subunits, alpha (α, 36 kD, this article),beta (β, 38 kD), andgamma (γ, 52 kD). The rate of formation of the ternary complex is modulated by thephosphorylation state of eIF2α.[ 6] EIF-2 kinases plays a key role in regulating theintegrated stress response .[ 7]
Clinical significance [ edit ] After reperfusion following brainischemia , there is inhibition of neuron protein synthesis due to phosphorylation of eIF2α. There is colocalization between phosphorylated eIF2α andcytosolic cytochrome c , which is released frommitochondria inapoptosis . Phosphorylated Eif2-alpha appeared before cytochrome c release, suggesting that phosphorylation of eIF2α triggers cytochrome c release during apoptotic cell death.[ 8]
Miceheterozygous for the S51Amutation become obese anddiabetic on a high-fat diet.Glucose intolerance resulted from reducedinsulin secretion, defective transport of proinsulin, and a reduced number of insulin granules inbeta cells . Hence proper functioning of eIF2α appears essential for preventing diet-inducedtype II diabetes .[ 9]
Dephosphorylation inhibitors [ edit ] Salubrinal is a selective inhibitor of enzymes that dephosphorylate eIF2α.[ 10] herpes simplex virus protein and inhibits viral replication. eIF2α phosphorylation is cytoprotective duringendoplasmic reticulum stress.[ 11] [ 12]
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