Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/tif211) on 'Ser-52' in response to low amino acid availability (PubMed:15611163). Plays a role as an activator of the general amino acid control (GAAC) pathway required for adapatation to amino acid starvation (PubMed:15821139). Converts phosphorylated eIF-2-alpha/tif211 either to a competitive inhibitor of translation initiation factor eIF-2B, leading to a global protein synthesis repression, and thus to a reduced overall utilization of amino acids, or to a translational initiation activation of specific mRNAs, such as the transcriptional activator fil1, and hence allowing fil1-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:15821139). Binds uncharged tRNAs (By similarity). ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] The kinase activity is stimulated upon binding to uncharged tRNAs. Homodimer; homodimerization is important for kinase activation by uncharged tRNAs. Interacts (via N-terminal RWD domain) with gcn1 (via N- and C-terminus); this interaction stimulates gcn2 kinase activity in a gcn20-dependent manner in response to amino acid starvation. Interacts (via N-terminus) with the gcn1-gcn20 complex on translating ribosomes in amino acid-starved cells; gcn1 may bind near the ribosomal A-site and promotes the transfer of uncharged tRNAs from the A-site to the tRNA-binding domain in gcn2 for its subsequent kinase activation, and hence allowing fil1 translational activation and derepression of amino acid biosynthetic genes. Autophosphorylated. Decreases translation of transcription factor fil1 (PubMed:29432178). Decreases RNA level and translation of genes involved the response to amino acid starvation (PubMed:29432178). Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.