Phosphorylated EIF2AK1 phosphorylates EIF2S1 (eIF2-alpha) on serine-52 (homologous to serine-51 of the rabbit homologue) (inferred from rabbit and mouse homologs). Phosphothreonine 488 (homologous to phosphothreonine-485 of the mouse homolog) of EIF2AK1 is required for kinase activity of EIF2AK1 acting on EIF2S1 (inferred from mouse homologs). Phosphorylated EIF2S1 in the EIF2alpha complex causes the complex to bind more tightly to the GTP exchange factor EIF2B, which inhibits exchange of GDP for GTP, and hence inhibits recycling of EIF2alpha to the active (GTP-bound) state. The result is a general decrease of translation in the cell, with a few mRNAs, such as ATF4, that possess upstream ORFs exhibiting increased translation. The decrease in translation of globin mRNAs in particular helps to maintain a 1:1 balance of heme and globin in erythropoiesis during heme deficiency.