IFN-induced dsRNA-dependent serine/threonine-protein kinasethat phosphorylates the alpha subunit of eukaryotic translationinitiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in theinnate immune response to viral infection . Inhibits viralreplication via the integrated stress response (ISR) : EIF2S1/eIF-2-alpha phosphorylation in response to viral infection convertsEIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resultingto a shutdown of cellular and viral protein synthesis, whileconcomitantly initiating the preferential translation of ISR-specificmRNAs, such as the transcriptional activator ATF4. Exerts itsantiviral activity on a wide range of DNA and RNA viruses includinghepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Also involved in the regulation of signaltransduction, apoptosis, cell proliferation and differentiation:phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity andphosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating itsubiquitination and proteosomal degradation. Either asan adapter protein and/or via its kinase activity, can regulate varioussignaling pathways (p38 MAP kinase, NF-kappa-B and insulin signalingpathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokinesand IFNs. Activatesthe NF-kappa-B pathway via interaction with IKBKB and TRAF family ofproteins and activates the p38 MAP kinase pathway via interaction withMAP2K6. Can act asboth a positive and negative regulator of the insulin signaling pathway (ISP). Negatively regulates ISP by inducing theinhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5Awhich activates FOXO1, which in turn up-regulates the expression ofinsulin receptor substrate 2 (IRS2). Can regulateNLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2and NLRC4 inflammasomes. Plays a role in theregulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin. [1-12]

MAGDLSAGFFMEELNTYRQKQGVVLKYQELPNSGPPHDRRFTFQVIIDGREFPEGEGRSKKEAKNAAAKLAVEILNKEKKAVSPLLLTTTNSSEGLSMGNYIGLINRIAQKKRLTVNYEQCASGVHGPEGFHYKCKMGQKEYSIGTGSTKQEAKQLAAKLAYLQILSEETSVKSDYLSSGSFATTCESQSNSLVTSTLASESSSEGDFSADTSEINSNSDSLNSSSLLMNGLRNNQRKAKRSLAPRFDLPDMKETKYTVDKRFGMDFKEIELIGSGGFGQVFKAKHRIDGKTYVIKRVKYNNEKAEREVKALAKLDHVNIVHYNGCWDGFDYDPETSDDSLESSDYDPENSKNSSRSKTKCLFIQMEFCDKGTLEQWIEKRRGEKLDKVLALELFEQITKGVDYIHSKKLIHRDLKPSNIFLVDTKQVKIGDFGLVTSLKNDGKRTRSKGTLRYMSPEQISSQDYGKEVDLYALGLILAELLHVCDTAFETSKFFTDLRDGIISDIFDKKEKTLLQKLLSKKPEDRPNTSEILRTLTVWKKSPEKNERHTC