EIF2S1

Eukaryotic translation initiation factor 2 subunit 1 is a protein that in humans is encoded by the EIF2S1 gene.

Function

The protein encoded by this gene is the alpha subunit of the translation initiation factor eIF2 complex which catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, eIF2, and GTP. eIF2 is composed of 3 nonidentical subunits, alpha (36 kD, this article), beta (38 kD), and gamma (52 kD). The rate of formation of the ternary complex is modulated by the phosphorylation state of eIF2-alpha.

Clinical significance

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