EIF2S1

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

Function
The is_associated_with::protein encoded by this gene is the alpha subunit of the translation initiation factor is_associated_with::eIF2 complex which catalyzes the first regulated step of is_associated_with::protein synthesis initiation, promoting the binding of the initiator tRNA to is_associated_with::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 is_associated_with::phosphorylation state of eIF2-alpha.

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

Mice is_associated_with::heterozygous for the S51A is_associated_with::mutation become obese and diabetic on a high-fat diet. is_associated_with::Glucose intolerance resulted from reduced is_associated_with::insulin secretion, defective transport of proinsulin, and a reduced number of insulin granules in is_associated_with::beta cells. Hence proper functioning of EIF2S1 appears essential for preventing diet-induced type II diabetes.

Dephosphorylation inhibitors
is_associated_with::Salubrinal is a selective inhibitor of enzymes that dephosphorylate EIF2-alpha. Salubrinal also blocks EIF2-alpha dephosphorylation by a is_associated_with::herpes simplex virus protein and inhibits viral replication. EIF2-alpha phosphorylation is cytoprotective during is_associated_with::endoplasmic reticulum stress.