Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (eIF2alpha), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis (PubMed:10677345). May phosphorylate eIF2alpha during hypoxia (PubMed:20733002). Proposed to have a role in alleviating endoplasmic reticulum stress (PubMed:10677345, PubMed:11779465, PubMed:16184190). 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 (By similarity). Forms dimers with HSPA5/BIP in resting cells. Oligomerizes in ER-stressed cells (By similarity). Expressed in intestinal cells. By ER stress. The lumenal domain senses perturbations in protein folding in the ER, probably through reversible interaction with HSPA5/BIP. Autophosphorylated. N-glycosylated. After L2 growth stage movement is subdued and development is stunted. Increased sensitivity to tunicamycin which induces an unfolded protein response symptomatic of endoplasmic reticulum stress. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.