Eukaryotic Translation Initiation Factor 2 Alpha Kinase 1 (EIF2aK1)

The HRI gene is localized to 7p22 where its 3""" end slightly overlaps the 3""" end of the gene JTV1. The two genes are transcribed from opposite strands. Studies in rat and rabbit suggest that the HRI gene product phosphorylates the alpha subunit of eukaryotic initiation factor 2. Its kinase activity is induced by low levels of heme and inhibited by the presence of heme. There are two mammalian eIF-2 alpha kinases, the double-stranded RNA-dependent kinase (PKR) and heme-regulated inhibitor kinase (HRI), both of which are responsible for the phosphorylation of the alpha subunit of eIF-2 at serine 51, one of the best-characterized mechanisms for down-regulating protein synthesis in higher eukaryotes in response to various stress conditions.