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: 1) activation by a) double-stranded RNA generated during the course of viral infection b) heparin 2) binding to dsRNA facilitates dimerization, autophosphorylation, activation 3) autophosphorylation in the activation loop 4) autophosphorylated on several Ser & Thr 5) autophosphorylation of Thr-451 is dependent on Thr-446 & is stimulated by dsRNA binding & dimerization 6) autophosphorylation apparently leads to the activation 4) phosphorylation of translation initiation factor EIF2S1 - inhibition of protein synthesis initiation 5) 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

General

multisubunit protein serine/threonine kinase

Properties

SIZE: entity length = 551 aa MW = 62 kD STATE: active state MOTIF: DRBM 1 {9-77} Ser phosphorylation site {S83} Thr phosphorylation site {T88} Thr phosphorylation site {T89} Thr phosphorylation site {T90} DRBM 2 {100-167} Ser phosphorylation site {S242} Thr phosphorylation site {T255} Thr phosphorylation site {T258} kinase domain SITE: 267-538 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 273-281 ATP-binding site NAME: ATP-binding site SITE: 296-296 repeat {331-357} MOTIF: consensus repeat {331-343} consensus repeat {345-357} aspartate residue {D414} Thr phosphorylation site {T446} Thr phosphorylation site {T451} MISC-INFO: RECOGNITION-MOTIF :SEQUENCE SEL[S*]RR :REF " - Kemp BE, Pearson RB. Protein kinase recognition sequence motifs. Trends Biochem Sci. 1990 Sep;15(9):342-6. Review. PMID: 2238044"

Database Correlations

OMIM 176871 UniProt P19525 PFAM correlations Kegg hsa:5610 ENZYME 2.7.11.1

References

UniProt accession P19525