Endogenous

EIF2AK2

Interferon-induced double-stranded RNA-activated protein kinase

EIF2AK2 ;
PKR ;
PRKR ;
Interferon-induced ;
double-stranded RNA-activated protein kinase ;
Eukaryotic translation initiation factor 2-alpha kinase 2 ;
eIF-2A protein kinase 2 ;
Interferon-inducible RNA-dependent protein kinase ;
P1/eIF-2A protein k

The protein encoded by this gene is a serine/threonine protein kinase that is activated by autophosphorylation after binding to dsRNA. The activated form of the encoded protein can phosphorylate translation initiation factor EIF2S1, which in turn inhibits protein synthesis. This protein is also activated by manganese ions and heparin. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2011],

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.,

Cytoplasm . Nucleus . Cytoplasm, perinuclear region . Nuclear localization is elevated in acute leukemia, myelodysplastic syndrome (MDS), melanoma, breast, colon, prostate and lung cancer patient samples or cell lines as well as neurocytes from advanced Creutzfeldt-Jakob disease patients. .

>>Cell cycle ;
>>p53 signaling pathway ;
>>Cellular senescence ;
>>Human T-cell leukemia virus 1 infection