GCN2: Proteins and Enzymes

GCN2, also known as EIF2AK4, is a widely expressed 190 kDa ribosome-associated Ser/Thr kinase that plays an important role in the control of protein translation. In response to amino acid deprivation or UV irradiation, GCN2 phosphorylates the alpha subunit of eukaryotic initiation factor 2 (eIF2 alpha) at Ser51 and induces a delay in entry to S phase of the cell cycle. Increased GCN2 activity in solid tumors enhances the production of amino acids and contributes to tumor cell survival in conditions of nutrient deprivation. GCN2 contains an RWD domain (aa 21-134), a pseudo-kinase domain (aa 296-539), a catalytic domain (aa 590-1001), and a histidyl tRNA synthase-like domain (aa 1022-1493) followed by a C-terminal ribosome interacting region. Alternate splicing generates an isoform with a short deletion in the kinase domain and an isoform that is truncated at the N-terminal end of the kinase domain.