Target General Infomation
Target ID
Former ID
Target Name
Interferon-induced, double-stranded RNA-activated protein kinase
Gene Name
Eukaryotic translation initiation factor 2-alpha kinase 2; Interferon-inducible RNA-dependent protein kinase; P1/eIF-2A protein kinase; PKR; Proteinkinase RNA-activated; Tyrosine-protein kinase EIF2AK2; eIF-2A protein kinase 2; p68 kinase; EIF2AK2
Target Type
IFN-induced dsRNA-dependent serine/threonine-protein kinase which plays a key role in the innate immune response to viral infection and is also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation. Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1). Inhibits viral replication via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (EIF2S1), this phosphorylation impairs the recycling of EIF2S1 between successive rounds of initiation leading to inhibition of translation which eventually results in shutdown of cellular and viral protein synthesis. Also 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 and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteosomal degradation. Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-Band insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs. Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6. Can act as both a positive and negative regulator of the insulin signaling pathway (ISP). Negatively regulates ISP by inducing the inhibitory 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 of insulin receptor substrate 2 (IRS2). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes. Can trigger apoptosis via FADD-mediated activation of CASP8. Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin.
BioChemical Class
UniProt ID
EC Number
Inhibitor ASN-11124542 Drug Info [526682]
indirubin derivative E804 Drug Info [531498]
NU6140 Drug Info [531498]
PANTHER Pathway Apoptosis signaling pathway
Pathway Interaction Database Signaling events mediated by TCPTP
Ceramide signaling pathway
PDGFR-beta signaling pathway
Reactome ISG15 antiviral mechanism
WikiPathways Type II interferon signaling (IFNG)
Host Interactions with Influenza Factors
Integrated Pancreatic Cancer Pathway
Translation Factors
Ref 526682Small molecule inhibitors of the RNA-dependent protein kinase. Biochem Biophys Res Commun. 2003 Aug 15;308(1):50-7.
Ref 531498Identification of new inhibitors of protein kinase R guided by statistical modeling. Bioorg Med Chem Lett. 2011 Jul 1;21(13):4108-14.

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