eIF-2-alpha kinase GCN2 (Eif2ak4)

Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on'Ser-52' in response to low amino acid availability (PubMed:10504407, PubMed:10655230, PubMed:12176355, PubMed:12215525, PubMed:15213227, PubMed:16054071, PubMed:16176978, PubMed:16121183, PubMed:15774759, PubMed:16601681, PubMed:26102367). Plays a role as an activator of the integrated stress response (ISR) required for adapatation to amino acid starvation.

Converts phosphorylated eIF-2-alpha/EIF2S1 either to a competitive inhibitor of the translation initiation factor eIF-2B, leading to a global protein synthesis repression, and thus to a reduced overall use of amino acids, or into a translational initiation activation of specific mRNAs, such as the transcriptional activator ATF4, and hence enabling ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:10655230, PubMed:11106749, PubMed:12176355, PubMed:15213227, PubMed:16176978, PubMed:26102367). Binds uncharged tRNAs (By similarity).