EIF2AK2 (PKR) review notes

Literature search (no deep-research provider available)

Sources checked: the UniProt entry P19525 (curated FUNCTION, SUBUNIT, SUBCELLULAR LOCATION
and ACTIVITY REGULATION text); every GOA-cited publication cached by
just fetch-gene-pmids human EIF2AK2 (49 papers; most are abstract-only); and the cached
Reactome reactions for the PKR pathway (R-HSA-98336xx/9835xxx/9839xxx). Context only: the integrated stress response module (module proposed in ai4curation/ai-gene-review#5904),
which models PKR as one realizer of the eIF2alpha kinase step, and GO-CAM 66b5638000001589, which is about PERK and contains no PKR activity.

Key findings

• Core activity: dsRNA-activated eIF2alpha kinase PMID:1695551.
• dsRNA binding through the N-terminal dsRBMs PMID:1351683.
• Antiviral role through translational control PMID:19189853.
• IFN-beta amplification through eIF2alpha phosphorylation, not direct signalling PMID:22948139.
• Dual specificity: tyrosine autophosphorylation PMID:16373505 and CDK1 Tyr4 PMID:20395957.
• Secondary substrates and signalling (non-core): MKK6 and p38 PMID:15229216, TRAF-NF-kappaB PMID:15121867, PPP2R5A PMID:10866685, NFAR/ILF3 PMID:21123651, and the NLRP3 inflammasome PMID:22801494, whose role has been questioned by later mouse studies (not cached here).
• Location: mainly cytoplasmic/cytosolic, with a minor active nuclear pool PMID:21072047.

Curation decisions

• The 58 bare protein-binding IPI rows are REMOVEd under the protein-binding policy. Identical protein binding is MODIFYed to protein homodimerization activity.
• The general protein kinase activity and kinase activity rows are MODIFYed to protein serine/threonine kinase activity, or to eIF2alpha kinase activity where eIF2alpha was the substrate assayed.
• Cytoplasm rows are MODIFYed to cytosol. Nucleus and nucleoplasm rows are kept as non-core.
• Protein phosphatase regulator activity is REMOVEd, because PKR regulates PP2A by phosphorylating B56alpha, not as a regulatory subunit.
• Cellular response to amino acid starvation: the ARBA IEA row is marked as over-annotated, because amino-acid sensing is the GCN2 branch. The IMP row from PMID:25329545 is UNDECIDED, because the abstract does not describe a PKR experiment.
• NEW: integrated stress response signaling (GO:0140467). Comparator: EIF2AK1 carries it by IDA.