double-stranded RNA-dependent protein kinase (PKR, PRKR, EIF2AK2, protein kinase I, interferon-induced double-stranded RNA-activated protein kinase, interferon-inducible RNA-dependent protein kinase, protein kinase RNA-activated, p68 kinase, P1/eIF-2A protein kinase, serine/threonine protein kinase R)

Function

• activation by
  • double-stranded RNA generated during the course of viral infection
  • heparin
• binding to dsRNA facilitates dimerization, autophosphorylation, activation
• autophosphorylation in the activation loop
• autophosphorylated on several Ser & Thr
• autophosphorylation of Thr-451 is dependent on Thr-446 & is stimulated by dsRNA binding & dimerization
• autophosphorylation apparently leads to the activation
• phosphorylation of translation initiation factor EIF2S1
  • inhibition of protein synthesis initiation
• activity is markedly stimulated by Mn+2

Pathology

• inhibited by vaccinia virus protein E3, HCV E2, HCV NS5A, influenza A NS1 probably via dsRNA sequestering

More general terms

• serine/threonine kinase
• multisubunit protein

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5610
• OMIM: https://mirror.omim.org/entry/176871
• UniProt: http://www.uniprot.org/uniprot/P19525.html