Catalytic activity:ATP + a protein = ADP + a phosphoprotein. ,enzyme regulation:Activity is markedly stimulated by manganese ions. Besides dsRNA , heparin is a potent activator of the kinase. Binding to dsRNA is required for dimerization leading to autophosphorylation in the activation loop and stimulation of function. Inhibited by vaccinia virus protein E3 , probably via dsRNA sequestering. ,Function:Following activation by double-stranded RNA in the presence of ATP , the kinase becomes autophosphorylated and can catalyze the phosphorylation of the translation initiation factor EIF2S1 , which leads to an inhibition of the initiation of protein synthesis. Double-stranded RNA is generated during the course of a viral infection. ,induction:By interferon. ,PTM:Autophosphorylated on several Ser and Thr residues. Autophosphorylation of Thr-451 is dependent on Thr-446 and is stimulated by dsRNA binding and dimerization. Autophosphorylation apparently leads to the activation of the kinase. ,similarity:Belongs to the protein kinase superfamily. ,similarity:Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily. ,similarity:Contains 1 protein kinase domain. ,similarity:Contains 2 DRBM (double-stranded RNA-binding) domains. ,subunit:Homodimer. Interacts with STRBP (By similarity) . Interacts with DNAJC3. Inhibited by direct interaction with viral proteins such as HCV E2 , HCV NS5A and influenza A NS1. Activated by the interaction with HIV-1 Tat. ,
展开内容