Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Perturbation in protein folding in the endoplasmic reticulum (ER) promotes reversible dissociation from HSPA5/BIP and oligomerization, resulting in transautophosphorylation and kinase activity induction. Forms dimers with HSPA5/BIP in resting cells. Oligomerizes in ER-stressed cells (By similarity). By ER stress. The lumenal domain senses perturbations in protein folding in the ER, probably through reversible interaction with HSPA5/BIP. Autophosphorylated. N-glycosylated. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.