EIF2AK2 (PKR) is an interferon-inducible cytosolic serine/threonine kinase, one of the four vertebrate eIF2alpha kinases. It has two N-terminal double-stranded RNA-binding motifs and a C-terminal kinase domain. Binding of dsRNA (viral replication intermediates or structured host RNAs), the protein activator PRKRA/PACT, or ISGylation drives PKR homodimerization and autophosphorylation in the activation loop (Thr446/Thr451). Activated PKR phosphorylates eIF2alpha (EIF2S1) on Ser51, which blocks eIF2B-mediated recycling of eIF2 and represses cap-dependent translation initiation. This triggers the integrated stress response, including preferential ATF4 translation, and shuts down viral and host protein synthesis. Through this translational control PKR restricts many RNA and DNA viruses and amplifies IFN-beta induction. Viruses encode many PKR antagonists (E3, K3L, NS5A, E2, US11, NS1, TAR RNA), and cellular inhibitors (NPM1, NCK1, DNAJC3, TARBP2, DUS2) restrain its basal activity. PKR also phosphorylates secondary substrates (MKK6, PPP2R5A, ILF3, TP53, CDK1 Tyr4, among others) and contributes to p38 MAPK and NF-kappaB signalling, apoptosis and growth control. A minor nuclear pool exists. Heterozygous variants cause leukoencephalopathy with episodic neurological regression (LEUDEN) and dystonia 33.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001819 positive regulation of cytokine production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from mouse Pkr. PKR promotes production of IFN-beta and pro-inflammatory cytokines, largely through eIF2alpha-dependent translational effects on IkappaB-alpha and through NF-kappaB/p38 signalling. Reason: PKR contributes to cytokine induction downstream of dsRNA sensing, but this is a consequence of its kinase activity and signalling crosstalk, not its primary role. Kept as a non-core, consistent with the ISS row. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs PMID:22948139 These results suggest that an eIF-2Ξ±-dependent translation inhibition mechanism is sufficient to explain the PKR-mediated amplification of IPS-1-dependent IFN-Ξ² induction by foreign RNA |
| GO:0001819 positive regulation of cytokine production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Pkr for positive regulation of cytokine production. Reason: Same claim as the IEA row; supported in human cells for IFN-beta induction (PMID:22948139). Downstream, non-core. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs PMID:22948139 knockdown of PKR increased IΞΊB-Ξ± protein levels and impaired IFN-Ξ² induction |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MODIFY | Summary: High-throughput mRNA interactome capture (HEK293) recovered PKR among mRNA-bound proteins. Reason: PKR does bind RNA, but its defining RNA-binding activity is binding of double-stranded RNA through two N-terminal dsRBMs, which activates the kinase. The general term should be refined to double-stranded RNA binding, which the gene already carries by IDA/TAS. Proposed replacements: double-stranded RNA binding Supporting Evidence: PMID:22681889 Application to a human embryonic kidney cell line identified close to 800 proteins file:human/EIF2AK2/EIF2AK2-uniprot.txt Contains 2 dsRNA-binding domain (DRBM) |
| GO:0003725 double-stranded RNA binding | IDA PMID:21266579 Raftlin is involved in the nucleocapture complex to induce p... | ACCEPT | Summary: poly(I:C)-affinity purification followed by mass spectrometry identified PKR among poly(I:C)-binding proteins. Reason: dsRNA binding through the two N-terminal dsRBMs is the sensing activity that activates PKR; it is core. The cited paper is a poly(I:C)-capture proteomic study, and the activity is independently established by deletion mapping (PMID:1351683). Supporting Evidence: PMID:21266579 by sequential affinity chromatography with poly(U)- and poly(I:C)-Sepharose and subjected them to mass spectrometric analysis PMID:1351683 The double-stranded RNA (dsRNA)-binding domain of the human p68 kinase has been localized to the N-terminal half of the enzyme by using progressive deletion analysis and in vitro binding assays file:human/EIF2AK2/EIF2AK2-uniprot.txt Initially produced in an inactive form and is activated by binding to viral dsRNA, which causes dimerization and autophosphorylation in the activation loop and stimulation of function. |
| GO:0003725 double-stranded RNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation of dsRNA binding from the dsRBM (DSRM) domains. Reason: Correct and core; PKR has two dsRBMs (InterPro EIF2AK2_DSRM_1/2) that bind dsRNA and trigger activation. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt Contains 2 dsRNA-binding domain (DRBM) file:human/EIF2AK2/EIF2AK2-uniprot.txt InterPro; IPR014720; dsRBD_dom. |
| GO:0003725 double-stranded RNA binding | TAS PMID:1351683 Identification of double-stranded RNA-binding domains in the... | ACCEPT | Summary: TAS from the paper mapping the dsRNA-binding domains of human p68/PKR. Reason: Core sensing activity of PKR. Supporting Evidence: PMID:1351683 Deletions in either of two 12-amino-acid-long and arginine- or lysine-rich regions abrogated binding to dsRNA |
| GO:0004672 protein kinase activity | IDA PMID:12882984 Nucleophosmin interacts with and inhibits the catalytic func... | MODIFY | Summary: IDA: activated PKR phosphorylated recombinant nucleophosmin in vitro. Reason: Correct but general. PKR is a serine/threonine kinase (and dual-specificity for some tyrosines); the substrate phosphorylation shown supports protein serine/threonine kinase activity, which the gene already carries. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:12882984 purified recombinant NPM was phosphorylated by activated PKR |
| GO:0004672 protein kinase activity | IDA PMID:15229216 Protein kinase R (PKR) interacts with and activates mitogen-... | MODIFY | Summary: IDA: PKR phosphorylated MKK6 in vitro kinase assays. Reason: Correct but general; refine to protein serine/threonine kinase activity (MKK6 is phosphorylated on Ser/Thr). Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:15229216 In vitro kinase assays revealed that MKK6 was efficiently phosphorylated by PKR, and this could be inhibited by 2-aminopurine |
| GO:0004672 protein kinase activity | IDA PMID:18835251 Nck-1 interacts with PKR and modulates its activation by dsR... | MODIFY | Summary: IDA: Nck-1 is phosphorylated by PKR in vitro and Nck-1 limits PKR activation by dsRNA. Reason: Correct but general; refine to protein serine/threonine kinase activity. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:18835251 we uncovered that Nck-1 is substrate of PKR in vitro |
| GO:0004672 protein kinase activity | IDA PMID:22801494 Novel role of PKR in inflammasome activation and HMGB1 relea... | MODIFY | Summary: IDA: PKR autophosphorylation stimulated by poly(I:C)/ATP in macrophages during inflammasome activation. Reason: Kinase activity (autophosphorylation) is real; refine to protein serine/threonine kinase activity. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:22801494 Poly I:C/ATP significantly stimulated autophosphorylation of PKR |
| GO:0004672 protein kinase activity | IDA PMID:22948139 Protein kinase PKR amplification of interferon Ξ² induction o... | MODIFY | Summary: IDA: PKR activation correlated with eIF2alpha phosphorylation after dsRNA transfection or measles virus infection. Reason: The specific activity demonstrated is eIF2alpha kinase activity; refine to that term. Proposed replacements: eukaryotic translation initiation factor 2alpha kinase activity Supporting Evidence: PMID:22948139 we observed increased mRNA but decreased protein levels for the inhibitor of NF-ΞΊB signaling, IΞΊB-Ξ±, that correlated with PKR activation and eIF-2Ξ± phosphorylation |
| GO:0004672 protein kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: Combined electronic annotation of protein kinase activity from the kinase domain. Reason: Correct but general; the gene has well-supported, more specific kinase terms (eIF2alpha kinase; protein serine/threonine kinase). Proposed replacements: eukaryotic translation initiation factor 2alpha kinase activity protein serine/threonine kinase activity Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection file:human/EIF2AK2/EIF2AK2-uniprot.txt PROSITE; PS00108; PROTEIN_KINASE_ST; 1. |
| GO:0004672 protein kinase activity | IMP PMID:16216244 Double-stranded RNA-dependent protein kinase is required for... | MODIFY | Summary: IMP: a kinase-dead K296R dominant-negative PKR abolished poly(I:C)-stimulated PKR phosphorylation in MC3T3-E1 osteoblastic cells. Reason: The mutant demonstrates that K296 is needed for (auto)phosphorylation; refine to protein serine/threonine kinase activity. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:16216244 A dominant-negative mutant PKR cDNA, in which the amino acid lysine at 296 was replaced with arginine and which does not have catalytic activity, was transfected into mouse osteoblastic MC3T3-E1 cells |
| GO:0004672 protein kinase activity | IMP PMID:21123651 Phosphorylation of the NFAR proteins by the dsRNA-dependent ... | MODIFY | Summary: IMP: PKR activation by viral RNA enabled phosphorylation of NFAR1/NFAR2 (ILF3 isoforms) on Thr188 and Thr315. Reason: Refine to protein serine/threonine kinase activity (threonine phosphorylation of NFARs). Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:21123651 Activation of the dsRNA-activated protein kinase PKR by viral RNA enabled phosphorylation of NFAR1 and NFAR2 on Thr 188 and Thr 315 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:19189853 PKR protein kinase is activated by hepatitis C virus and inh... | ACCEPT | Summary: IDA: PKR is activated by HCV infection and phosphorylates eIF2alpha (Ser51). Reason: PKR is an established serine/threonine kinase with eIF2alpha as its principal substrate and several secondary substrates (MKK6, PPP2R5A, ILF3, TP53, NPM1). This term is the right level for the full substrate range; eIF2alpha kinase is the core specific activity. Supporting Evidence: PMID:19189853 HCV JFH1 infection of human hepatoma Huh-7 cells leads to the activation of IFN-inducible protein kinase PKR and phosphorylation of the translation initiation factor eIF2alpha file:human/EIF2AK2/EIF2AK2-uniprot.txt IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC-mapped IEA (EC 2.7.11.1). Reason: Consistent with experimental data. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection |
| GO:0004674 protein serine/threonine kinase activity | TAS PMID:1695551 Molecular cloning and characterization of the human double-s... | ACCEPT | Summary: TAS from the original cloning paper, which identified the Ser/Thr kinase catalytic domain. Reason: Correct. Supporting Evidence: PMID:1695551 including the catalytic domain characteristic of serine/threonine kinases |
| GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PAINT node PTN008315216 (HRI/PKR/PERK clade) in PTHR11042. Reason: PKR is the founding eIF2alpha kinase of the HRI/PKR/PERK clade; the node placement is sound and PKR's own experimental data are among the seeds. Core activity. Supporting Evidence: PMID:1695551 On activation by dsRNA in the presence of ATP, the kinase becomes autophosphorylated and can catalyze the phosphorylation of the alpha subunit of eIF2, which leads to an inhibition of the initiation of protein synthesis file:human/EIF2AK2/EIF2AK2-uniprot.txt IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection |
| GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity | IMP PMID:25329545 p58IPK is an inhibitor of the eIF2Ξ± kinase GCN2 and its loca... | ACCEPT | Summary: IMP from a study of eIF2alpha kinase cross-talk (p58IPK/DNAJC3, PERK, GCN2) in recombinant-protein-producing cells; the cached abstract foregrounds PERK and GCN2. Reason: The abstract does not show what was done to PKR, and the full text is not cached, so the curator's experimental basis cannot be checked here. The eIF2alpha kinase activity of PKR is not in doubt (PMID:1695551, PMID:19189853), so the row is accepted, deferring to the curator. Supporting Evidence: PMID:1695551 On activation by dsRNA in the presence of ATP, the kinase becomes autophosphorylated and can catalyze the phosphorylation of the alpha subunit of eIF2, which leads to an inhibition of the initiation of protein synthesis PMID:19189853 transient expression of PKR inhibited HCV replication in a kinase-dependent manner with concomitant increase of eIF2alpha phosphorylation |
| GO:0004694 eukaryotic translation initiation factor 2alpha kinase activity | TAS PMID:10866685 The B56alpha regulatory subunit of protein phosphatase 2A is... | ACCEPT | Summary: TAS: PKR described as a serine/threonine kinase that phosphorylates eIF2alpha to regulate protein synthesis. Reason: Core activity. Supporting Evidence: PMID:10866685 PKR is a cellular serine/threonine kinase that phosphorylates eukaryotic translation initiation factor 2alpha (eIF2alpha) to regulate protein synthesis |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Rhea/EC-mapped IEA for protein tyrosine kinase activity. Reason: PKR is a dual-specificity kinase: it autophosphorylates on Y101, Y162 and Y293 and phosphorylates CDK1 on Tyr4. This is real but secondary to its Ser/Thr activity on eIF2alpha. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage PMID:16373505 human PKR is a dual specificity kinase phosphorylated at Y101, Y162 and Y293 in vitro and in vivo PMID:20395957 PKR, Ser/Thr kinase, phosphorylates its new substrate Cdc2 at the Tyr 4 residue |
| GO:0004715 non-membrane spanning protein tyrosine kinase activity | IEA GO_REF:0000003 | KEEP AS NON CORE | Summary: EC 2.7.10.2-mapped IEA for non-membrane spanning protein tyrosine kinase activity. Reason: PKR is a soluble cytosolic kinase with documented tyrosine phosphorylation of CDK1 Tyr4, so the term is formally true; it is a secondary activity. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage |
| GO:0005515 protein binding | IPI PMID:10390359 Inhibition of the interferon-inducible protein kinase PKR by... | REMOVE | Summary: IPI for bare protein binding with PMID:10390359. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:10488152 Identification of the major phosphorylation site of the hepa... | REMOVE | Summary: IPI for bare protein binding with PMID:10488152. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:11160738 Latently expressed human herpesvirus 8-encoded interferon re... | REMOVE | Summary: IPI for bare protein binding with PMID:11160738. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:11773402 Detection of a novel unglycosylated form of hepatitis C viru... | REMOVE | Summary: IPI for bare protein binding with PMID:11773402. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:11836380 The herpes simplex virus type 1 U(S)11 protein interacts wit... | REMOVE | Summary: IPI for bare protein binding with PMID:11836380. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:12610133 Protein synthesis and endoplasmic reticulum stress can be mo... | REMOVE | Summary: IPI for bare protein binding with PMID:12610133. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:12882984 Nucleophosmin interacts with and inhibits the catalytic func... | REMOVE | Summary: IPI for bare protein binding with PMID:12882984. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:15121867 TRAF family proteins link PKR with NF-kappa B activation. | REMOVE | Summary: IPI for bare protein binding with PMID:15121867. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:15121867 TRAF family proteins link PKR with NF-kappa B activation. | REMOVE | Summary: IPI for bare protein binding with PMID:15121867. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:15121867 TRAF family proteins link PKR with NF-kappa B activation. | REMOVE | Summary: IPI for bare protein binding with PMID:15121867. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:15229216 Protein kinase R (PKR) interacts with and activates mitogen-... | REMOVE | Summary: IPI for bare protein binding with PMID:15229216. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:16288713 Interaction of recombinant human eIF2 subunits with eIF2B an... | REMOVE | Summary: IPI for bare protein binding with PMID:16288713. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:16785445 Molecular basis for PKR activation by PACT or dsRNA. | REMOVE | Summary: IPI for bare protein binding with PMID:16785445. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:16957780 Antiviral action of the tumor suppressor ARF. | REMOVE | Summary: IPI for bare protein binding with PMID:16957780. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:18096616 Interaction of human tRNA-dihydrouridine synthase-2 with int... | REMOVE | Summary: IPI for bare protein binding with PMID:18096616. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:18362360 The editing enzyme ADAR1 and the mRNA surveillance protein h... | REMOVE | Summary: IPI for bare protein binding with PMID:18362360. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:18835251 Nck-1 interacts with PKR and modulates its activation by dsR... | REMOVE | Summary: IPI for bare protein binding with PMID:18835251. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:18971339 Protein kinase PKR mutants resistant to the poxvirus pseudos... | REMOVE | Summary: IPI for bare protein binding with PMID:18971339. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:18971339 Protein kinase PKR mutants resistant to the poxvirus pseudos... | REMOVE | Summary: IPI for bare protein binding with PMID:18971339. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:20395957 New Cdc2 Tyr 4 phosphorylation by dsRNA-activated protein ki... | REMOVE | Summary: IPI for bare protein binding with PMID:20395957. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for bare protein binding with PMID:21903422. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for bare protein binding with PMID:21903422. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for bare protein binding with PMID:21903422. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for bare protein binding with PMID:21903422. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for bare protein binding with PMID:21903422. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for bare protein binding with PMID:21903422. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for bare protein binding with PMID:21903422. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for bare protein binding with PMID:21903422. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for bare protein binding with PMID:21903422. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for bare protein binding with PMID:21903422. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for bare protein binding with PMID:21903422. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for bare protein binding with PMID:21903422. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for bare protein binding with PMID:21903422. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:22801494 Novel role of PKR in inflammasome activation and HMGB1 relea... | REMOVE | Summary: IPI for bare protein binding with PMID:22801494. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:22801494 Novel role of PKR in inflammasome activation and HMGB1 relea... | REMOVE | Summary: IPI for bare protein binding with PMID:22801494. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:22801494 Novel role of PKR in inflammasome activation and HMGB1 relea... | REMOVE | Summary: IPI for bare protein binding with PMID:22801494. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:22801494 Novel role of PKR in inflammasome activation and HMGB1 relea... | REMOVE | Summary: IPI for bare protein binding with PMID:22801494. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | REMOVE | Summary: IPI for bare protein binding with PMID:23455922. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | REMOVE | Summary: IPI for bare protein binding with PMID:23455922. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: IPI for bare protein binding with PMID:32296183. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: IPI for bare protein binding with PMID:32296183. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: IPI for bare protein binding with PMID:32707033. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: IPI for bare protein binding with PMID:32707033. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: IPI for bare protein binding with PMID:32707033. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: IPI for bare protein binding with PMID:32707033. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: IPI for bare protein binding with PMID:32707033. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: IPI for bare protein binding with PMID:32707033. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI for bare protein binding with PMID:33961781. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:34035218 SARS-CoV-2 nucleocapsid protein impairs stress granule forma... | REMOVE | Summary: IPI for bare protein binding with PMID:34035218. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:34578187 Interactome Analysis of the Nucleocapsid Protein of SARS-CoV... | REMOVE | Summary: IPI for bare protein binding with PMID:34578187. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:34780058 SARS-CoV-2 nucleocapsid protein interacts with immunoregulat... | REMOVE | Summary: IPI for bare protein binding with PMID:34780058. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: IPI for bare protein binding with PMID:35271311. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: IPI for bare protein binding with PMID:35271311. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:36217029 A proteome-scale map of the SARS-CoV-2-human contactome. | REMOVE | Summary: IPI for bare protein binding with PMID:36217029. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:8576172 The P58 cellular inhibitor complexes with the interferon-ind... | REMOVE | Summary: IPI for bare protein binding with PMID:8576172. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:9143277 Evidence that hepatitis C virus resistance to interferon is ... | REMOVE | Summary: IPI for bare protein binding with PMID:9143277. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:9431994 Homologous regions of the alpha subunit of eukaryotic transl... | REMOVE | Summary: IPI for bare protein binding with PMID:9431994. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005515 protein binding | IPI PMID:9431994 Homologous regions of the alpha subunit of eukaryotic transl... | REMOVE | Summary: IPI for bare protein binding with PMID:9431994. PKR has many binding partners: activators (PRKRA/PACT), inhibitors (NPM1, NCK1, DNAJC3, DUS2, viral E2, NS5A, US11, K3L, vIRF-2, SARS-CoV-2 N), substrates (eIF2alpha, MKK6) and signalling partners (TRAF2/5/6). Reason: Bare protein binding is uninformative under the project protein-binding policy. Removing it does not dispute the reported interaction. The functionally meaningful parts are captured by the kinase activity terms, double-stranded RNA binding and homodimerization. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-mapped ATP binding from the protein kinase domain. Reason: PKR is an ATP-dependent kinase with a canonical ATP-binding site (K296; the K296R mutant is catalytically dead). Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. PMID:1695551 On activation by dsRNA in the presence of ATP, the kinase becomes autophosphorylated and can catalyze the phosphorylation of the alpha subunit of eIF2, which leads to an inhibition of the initiation of protein synthesis |
| GO:0005634 nucleus | EXP PMID:21029237 Modulation of tau phosphorylation by the kinase PKR: implica... | KEEP AS NON CORE | Summary: EXP: nuclear PKR detected in neurons/neuroblastoma cells (tau/GSK-3beta study). Reason: PKR is mostly cytoplasmic; a minor nuclear pool exists, increases when PKR is activated, and is enriched in some cancers. Its core eIF2alpha kinase function is cytosolic, so the nuclear location is kept as non-core. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt Nuclear localization is elevated in acute leukemia, myelodysplastic syndrome (MDS), melanoma, breast, colon, prostate and lung cancer patient samples or cell lines Reactome:R-HSA-9833635 The small fraction in the nucleus increases when PKR is activated by dimerization and phosphorylation |
| GO:0005634 nucleus | EXP PMID:21072047 Multiple forms of PKR present in the nuclei of acute leukemi... | KEEP AS NON CORE | Summary: EXP: active, post-translationally modified PKR forms found in nuclei of acute leukemia cells. Reason: PKR is mostly cytoplasmic; a minor nuclear pool exists, increases when PKR is activated, and is enriched in some cancers. Its core eIF2alpha kinase function is cytosolic, so the nuclear location is kept as non-core. Supporting Evidence: PMID:21072047 Biochemical analysis demonstrated that nuclear PKR is an active kinase that can respond to stress file:human/EIF2AK2/EIF2AK2-uniprot.txt Nuclear localization is elevated in acute leukemia, myelodysplastic syndrome (MDS), melanoma, breast, colon, prostate and lung cancer patient samples or cell lines |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA (is_active_in nucleus) from the eIF2alpha kinase family. Reason: PKR is mostly cytoplasmic; a minor nuclear pool exists, increases when PKR is activated, and is enriched in some cancers. Its core eIF2alpha kinase function is cytosolic, so the nuclear location is kept as non-core. The family-level placement is plausible because a nuclear pool of active PKR has been shown. Supporting Evidence: PMID:21072047 Biochemical analysis demonstrated that nuclear PKR is an active kinase that can respond to stress |
| GO:0005634 nucleus | IDA PMID:26705305 Moco biosynthesis and the ATAC acetyltransferase engage tran... | KEEP AS NON CORE | Summary: IDA: nuclear and cytoplasmic PKR in a study of MPT synthase/ATAC inhibition of PKR. Reason: PKR is mostly cytoplasmic; a minor nuclear pool exists, increases when PKR is activated, and is enriched in some cancers. Its core eIF2alpha kinase function is cytosolic, so the nuclear location is kept as non-core. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt Nuclear localization is elevated in acute leukemia, myelodysplastic syndrome (MDS), melanoma, breast, colon, prostate and lung cancer patient samples or cell lines |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA from UniProt subcellular location (nucleus). Reason: PKR is mostly cytoplasmic; a minor nuclear pool exists, increases when PKR is activated, and is enriched in some cancers. Its core eIF2alpha kinase function is cytosolic, so the nuclear location is kept as non-core. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt Nuclear localization is elevated in acute leukemia, myelodysplastic syndrome (MDS), melanoma, breast, colon, prostate and lung cancer patient samples or cell lines |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9833635 | KEEP AS NON CORE | Summary: Reactome places p-PKR in the nucleoplasm (Reactome:R-HSA-9833635: nuclear translocation of the activated dimer, or nuclear phosphorylation of TP53 or SPHK1). Reason: The nuclear pool of activated PKR is documented but minor; nuclear substrates (TP53, SPHK1) are secondary roles. Supporting Evidence: Reactome:R-HSA-9833635 The small fraction in the nucleus increases when PKR is activated by dimerization and phosphorylation |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9836362 | KEEP AS NON CORE | Summary: Reactome places p-PKR in the nucleoplasm (Reactome:R-HSA-9836362: nuclear translocation of the activated dimer, or nuclear phosphorylation of TP53 or SPHK1). Reason: The nuclear pool of activated PKR is documented but minor; nuclear substrates (TP53, SPHK1) are secondary roles. Supporting Evidence: Reactome:R-HSA-9833635 The small fraction in the nucleus increases when PKR is activated by dimerization and phosphorylation |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9836617 | KEEP AS NON CORE | Summary: Reactome places p-PKR in the nucleoplasm (Reactome:R-HSA-9836617: nuclear translocation of the activated dimer, or nuclear phosphorylation of TP53 or SPHK1). Reason: The nuclear pool of activated PKR is documented but minor; nuclear substrates (TP53, SPHK1) are secondary roles. Supporting Evidence: Reactome:R-HSA-9833635 The small fraction in the nucleus increases when PKR is activated by dimerization and phosphorylation |
| GO:0005737 cytoplasm | EXP PMID:21029237 Modulation of tau phosphorylation by the kinase PKR: implica... | MODIFY | Summary: EXP: cytoplasmic PKR in neurons (Alzheimer disease brain and SH-SY5Y cells). Reason: PKR is cytoplasmic, but the more specific location is the cytosol, where it binds dsRNA and ribosome-associated eIF2alpha. Refine to cytosol, which the gene carries by HPA IDA, by PMID:26705305 IDA and by Reactome. Proposed replacements: cytosol Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. file:human/EIF2AK2/EIF2AK2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:22214662 The RAX/PACT-PKR stress response pathway promotes p53 sumoyl... | MODIFY | Summary: EXP: cytoplasmic PKR in a RAX/PACT-PKR-p53 signalling study. Reason: PKR is cytoplasmic, but the more specific location is the cytosol, where it binds dsRNA and ribosome-associated eIF2alpha. Refine to cytosol, which the gene carries by HPA IDA, by PMID:26705305 IDA and by Reactome. Proposed replacements: cytosol Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. file:human/EIF2AK2/EIF2AK2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:26705305 Moco biosynthesis and the ATAC acetyltransferase engage tran... | MODIFY | Summary: EXP: cytoplasmic PKR (MPT synthase/ATAC study). Reason: PKR is cytoplasmic, but the more specific location is the cytosol, where it binds dsRNA and ribosome-associated eIF2alpha. Refine to cytosol, which the gene carries by HPA IDA, by PMID:26705305 IDA and by Reactome. Proposed replacements: cytosol Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. file:human/EIF2AK2/EIF2AK2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MODIFY | Summary: IBA (is_active_in cytoplasm) from the eIF2alpha kinase family. Reason: PKR is cytoplasmic, but the more specific location is the cytosol, where it binds dsRNA and ribosome-associated eIF2alpha. Refine to cytosol, which the gene carries by HPA IDA, by PMID:26705305 IDA and by Reactome. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000113601 SUPPORTS TRANSFER The family-level IBD node (PTHR11042, seeded by many soluble kinases including WEE1-like members) correctly places these kinases in the cytoplasm. It stops at cytoplasm, whereas PKR's activity is in the cytosol. Proposed replacements: cytosol Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. file:human/EIF2AK2/EIF2AK2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | IDA PMID:15121867 TRAF family proteins link PKR with NF-kappa B activation. | MODIFY | Summary: IDA: PKR colocalizes with TRAF proteins in the cytoplasm by confocal microscopy. Reason: PKR is cytoplasmic, but the more specific location is the cytosol, where it binds dsRNA and ribosome-associated eIF2alpha. Refine to cytosol, which the gene carries by HPA IDA, by PMID:26705305 IDA and by Reactome. Proposed replacements: cytosol Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. file:human/EIF2AK2/EIF2AK2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | IDA PMID:21123651 Phosphorylation of the NFAR proteins by the dsRNA-dependent ... | MODIFY | Summary: IDA: PKR is active in the cytoplasm, where it phosphorylates NFAR proteins retained on ribosomes. Reason: PKR is cytoplasmic, but the more specific location is the cytosol, where it binds dsRNA and ribosome-associated eIF2alpha. Refine to cytosol, which the gene carries by HPA IDA, by PMID:26705305 IDA and by Reactome. Proposed replacements: cytosol Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. file:human/EIF2AK2/EIF2AK2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: IEA from UniProt subcellular location (cytoplasm). Reason: PKR is cytoplasmic, but the more specific location is the cytosol, where it binds dsRNA and ribosome-associated eIF2alpha. Refine to cytosol, which the gene carries by HPA IDA, by PMID:26705305 IDA and by Reactome. Proposed replacements: cytosol Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. file:human/EIF2AK2/EIF2AK2-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: IDA from the Human Protein Atlas immunofluorescence (cytosol). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | IDA PMID:26705305 Moco biosynthesis and the ATAC acetyltransferase engage tran... | ACCEPT | Summary: IDA: cytosolic PKR (MPT synthase/ATAC study). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1015702 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-1015702 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1169406 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-1169406 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1678841 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-1678841 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-168896 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-168896 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9833436 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9833436 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9833635 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9833635 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9833723 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9833723 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9833777 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9833777 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9833820 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9833820 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9833973 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9833973 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9834807 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9834807 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9834809 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9834809 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9834821 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9834821 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835121 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9835121 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835189 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9835189 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835328 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9835328 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835358 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9835358 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835385 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9835385 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835411 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9835411 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835443 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9835443 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835454 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9835454 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835885 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9835885 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835940 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9835940 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835944 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9835944 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835949 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9835949 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835992 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9835992 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9836159 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9836159 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9836184 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9836184 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9836322 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9836322 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9836383 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9836383 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9836404 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9836404 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9836435 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9836435 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9836449 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9836449 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9836500 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9836500 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9836515 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9836515 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9836606 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9836606 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9836664 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9836664 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9836702 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9836702 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9839016 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9839016 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9839025 | ACCEPT | Summary: Reactome places PKR in the cytosol for reaction Reactome:R-HSA-9839025 (PKR activation, inhibition, or substrate phosphorylation in the IFN/PKR pathway). Reason: PKR is a soluble cytosolic kinase that phosphorylates eIF2alpha; the cytosol is the site of its core activity. Supporting Evidence: Reactome:R-HSA-9833635 PKR (EIF2AK2) is primarily localized in the cytoplasm. |
| GO:0005840 ribosome | TAS PMID:10390359 Inhibition of the interferon-inducible protein kinase PKR by... | KEEP AS NON CORE | Summary: TAS: PKR is described in connection with ribosome-associated translational control (HCV E2 paper). Reason: PKR associates with ribosomes, which places it near its substrate eIF2alpha; for example, it co-fractionates with US11 in the S100 ribosomal fraction. It is not a ribosome component, so the location is kept as non-core context. Supporting Evidence: PMID:11836380 the proteins biochemically colocalize in the S100 ribosomal fraction |
| GO:0006446 regulation of translational initiation | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTHR11042 for regulation of translational initiation. Reason: eIF2alpha phosphorylation by PKR blocks ternary-complex recycling and so inhibits translation initiation. This is the core process, and the regulation-level term is appropriate for the family. Supporting Evidence: PMID:1695551 On activation by dsRNA in the presence of ATP, the kinase becomes autophosphorylated and can catalyze the phosphorylation of the alpha subunit of eIF2, which leads to an inhibition of the initiation of protein synthesis |
| GO:0008285 negative regulation of cell population proliferation | TAS PMID:1351683 Identification of double-stranded RNA-binding domains in the... | KEEP AS NON CORE | Summary: TAS: dsRNA-binding mutants of PKR failed to cause slow growth in yeast. Reason: PKR has antiproliferative activity, a consequence of translational arrest and apoptosis signalling. True but not a core function. Supporting Evidence: PMID:1351683 in an in vivo growth inhibition assay in the yeast Saccharomyces cerevisiae, these mutants failed to exhibit a slow-growth phenotype PMID:16373505 tyrosine phosphorylation of PKR mediates the antiviral and antiproliferative properties of the kinase through its ability to control translation |
| GO:0009615 response to virus | IMP PMID:19189853 PKR protein kinase is activated by hepatitis C virus and inh... | MODIFY | Summary: IMP: PKR knockdown increased HCV replication about 10-fold. Reason: The phenotype is an antiviral defence, so refine to defense response to virus, which the gene carries by IEP. Proposed replacements: defense response to virus Supporting Evidence: PMID:19189853 PKR is activated by HCV infection and plays a critical antiviral role through inhibition of viral protein translation |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: HDA: PKR was detected in an NK-cell membrane proteome. The authors note that many detected proteins are only transiently associated with membranes. Reason: PKR has no transmembrane segment or lipid anchor and is cytosolic; detection in a crude membrane fraction does not make it a membrane protein. Supporting Evidence: PMID:19946888 The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes |
| GO:0016301 kinase activity | IDA PMID:21123651 Phosphorylation of the NFAR proteins by the dsRNA-dependent ... | MODIFY | Summary: IDA: kinase activity of PKR toward NFAR1/NFAR2. Reason: Correct but general; refine to protein serine/threonine kinase activity (Thr188/Thr315 phosphorylation). Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:21123651 Activation of the dsRNA-activated protein kinase PKR by viral RNA enabled phosphorylation of NFAR1 and NFAR2 on Thr 188 and Thr 315 |
| GO:0017148 negative regulation of translation | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for negative regulation of translation. Reason: Core outcome of eIF2alpha phosphorylation by PKR. Supporting Evidence: PMID:1695551 On activation by dsRNA in the presence of ATP, the kinase becomes autophosphorylated and can catalyze the phosphorylation of the alpha subunit of eIF2, which leads to an inhibition of the initiation of protein synthesis |
| GO:0017148 negative regulation of translation | IMP PMID:12610133 Protein synthesis and endoplasmic reticulum stress can be mo... | ACCEPT | Summary: IMP from a paper on HCV E2 inhibition of eIF2alpha kinases (PKR and PERK); abstract only. Reason: E2 relieves PKR-mediated translational inhibition, consistent with PKR negatively regulating translation. The core claim is well established, so the row is accepted, deferring to the curator on the full-text detail. Supporting Evidence: PMID:12610133 We previously reported that E2 modulates global translation through inhibition of the interferon-induced antiviral protein PKR PMID:1695551 On activation by dsRNA in the presence of ATP, the kinase becomes autophosphorylated and can catalyze the phosphorylation of the alpha subunit of eIF2, which leads to an inhibition of the initiation of protein synthesis |
| GO:0019888 protein phosphatase regulator activity | TAS PMID:10866685 The B56alpha regulatory subunit of protein phosphatase 2A is... | REMOVE | Summary: TAS: PKR phosphorylates the PP2A regulatory subunit B56alpha (PPP2R5A), which increases PP2A holoenzyme activity. Reason: PKR is not itself a phosphatase regulatory subunit and does not bind PP2A to regulate it. It modulates PP2A indirectly as a kinase acting on B56alpha. That activity is captured by protein serine/threonine kinase activity, so this MF term misstates the mechanism. Supporting Evidence: PMID:10866685 our data indicate that PKR can modulate PP2A activity by phosphorylating B56alpha to regulate cellular activities |
| GO:0032722 positive regulation of chemokine production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA (Ensembl orthology) from mouse Pkr for positive regulation of chemokine production. Reason: A downstream inflammatory output of PKR signalling; peripheral. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs |
| GO:0032722 positive regulation of chemokine production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Pkr for positive regulation of chemokine production. Reason: As for the IEA row. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs |
| GO:0032874 positive regulation of stress-activated MAPK cascade | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA from mouse Pkr for positive regulation of stress-activated MAPK cascade. Reason: PKR promotes p38 activation by phosphorylating MKK6 after dsRNA stimulation. A real signalling role, but secondary to eIF2alpha control. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt 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 PMID:15229216 Our results indicate that the interaction of MKK6 and PKR provides a mechanism for regulating p38 MAPK activation in response to dsRNA stimulation |
| GO:0032874 positive regulation of stress-activated MAPK cascade | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Pkr for positive regulation of stress-activated MAPK cascade. Reason: As for the IEA row. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt 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 |
| GO:0033689 negative regulation of osteoblast proliferation | IMP PMID:16216244 Double-stranded RNA-dependent protein kinase is required for... | KEEP AS NON CORE | Summary: IMP: dominant-negative kinase-dead PKR in MC3T3-E1 osteoblastic cells increased cell growth and impaired calcification. Reason: This comes from a single dominant-negative cell-line study and reflects the general antiproliferative effect of PKR. It is kept as a non-core, context-specific phenotype. Supporting Evidence: PMID:16216244 The PKR-K/R mutant cells exhibited up-regulated cell growth and had low alkaline phosphatase (ALP) activity |
| GO:0034198 cellular response to amino acid starvation | IEA GO_REF:0000117 | UNDECIDED | Summary: IEA (ARBA, GO_REF:0000117) for cellular response to amino acid starvation. Reason: Amino-acid starvation is sensed by GCN2 (EIF2AK4) through uncharged tRNA, whereas PKR senses dsRNA, so this ARBA rule probably transfers a GCN2 property across the eIF2alpha kinase family. The same term also has an IMP row (PMID:25329545) whose basis cannot be checked from the abstract. Both rows are therefore left undecided, not removed. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection PMID:25329545 whereas GCN2 is the kinase that is activated following cold-shock/hypothermic culturing of mammalian cells |
| GO:0034198 cellular response to amino acid starvation | IMP PMID:25329545 p58IPK is an inhibitor of the eIF2Ξ± kinase GCN2 and its loca... | UNDECIDED | Summary: IMP from a study of eIF2alpha kinase cross-talk under recombinant-protein production stress; the abstract foregrounds PERK and GCN2. Reason: The cached abstract does not describe a PKR perturbation under amino-acid starvation, and the full text is unavailable. Amino-acid sensing is canonically a GCN2 function, but the curator's experimental basis cannot be checked, so the row is left undecided rather than removed. Supporting Evidence: PMID:25329545 PERK and GCN2 have overlapping functions since knockdown of one of these at the mRNA level is compensated for by the cell by up-regulating levels of the other |
| GO:0035455 response to interferon-alpha | IDA PMID:19840259 Double-stranded RNA-activated protein kinase inhibits hepati... | KEEP AS NON CORE | Summary: IDA: PKR knockdown reduced the suppression of the HCV replicon by low-dose IFN-alpha. Reason: PKR is an interferon-stimulated effector and contributes partially to IFN-alpha antiviral action. Peripheral to its kinase function. Supporting Evidence: PMID:19840259 Although the extent of suppression was significantly lower in stable PKR knockdown than control cells using a low concentration (2.5-5 U/ml) of IFN-alpha file:human/EIF2AK2/EIF2AK2-uniprot.txt INDUCTION: By type I interferons. |
| GO:0042802 identical protein binding | IPI PMID:16373505 Tyrosine phosphorylation acts as a molecular switch to full-... | MODIFY | Summary: IPI: tyrosine phosphorylation of PKR is required for its dimerization, dsRNA binding and activation. Reason: PKR self-association is a homodimer that is mechanistically required for activation. Refine identical protein binding to protein homodimerization activity. Proposed replacements: protein homodimerization activity Supporting Evidence: PMID:16373505 Site-specific tyrosine phosphorylation is essential for efficient dsRNA-binding, dimerization, kinase activation and eIF2alpha phosphorylation of PKR file:human/EIF2AK2/EIF2AK2-uniprot.txt Homodimer (PubMed:16179258, PubMed:31246429). |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IDA PMID:15121867 TRAF family proteins link PKR with NF-kappa B activation. | KEEP AS NON CORE | Summary: IDA: PKR expression activates NF-kappaB through TRAF2/TRAF5. Reason: PKR promotes canonical NF-kappaB activation through TRAFs and IKK. A real but secondary signalling role. Supporting Evidence: PMID:15121867 we show that the binding between PKR and TRAFs is functionally relevant, as observed by the absence of NF-ΞΊB activity upon PKR expression in cells genetically deficient in TRAF2 and TRAF5 file:human/EIF2AK2/EIF2AK2-uniprot.txt 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 |
| GO:0043410 positive regulation of MAPK cascade | IMP PMID:15229216 Protein kinase R (PKR) interacts with and activates mitogen-... | MODIFY | Summary: IMP: kinase-dead PKR blocked poly(I:C)-induced MKK3/6 phosphorylation and p38 activation. Reason: The evidence is specific to the p38 branch (MKK6 to p38). Refine to positive regulation of p38MAPK cascade. Proposed replacements: positive regulation of p38MAPK cascade Supporting Evidence: PMID:15229216 Expression of kinase-inactive PKR (K296R) in cells inhibited the poly(IC)-induced phosphorylation of MKK3/6 detected by phosphospecific antiserum |
| GO:0045071 negative regulation of viral genome replication | IEA GO_REF:0000107 | ACCEPT | Summary: IEA (orthology) for negative regulation of viral genome replication. Reason: PKR restricts replication of many viruses by shutting down translation. This antiviral output is core to its biological role. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection PMID:19189853 transient expression of PKR inhibited HCV replication in a kinase-dependent manner with concomitant increase of eIF2alpha phosphorylation |
| GO:0045071 negative regulation of viral genome replication | IMP PMID:19189853 PKR protein kinase is activated by hepatitis C virus and inh... | ACCEPT | Summary: IMP: PKR knockdown raised HCV titres; PKR expression inhibited HCV replication in a kinase-dependent way. Reason: Direct human evidence for the core antiviral role. Supporting Evidence: PMID:19189853 transient expression of PKR inhibited HCV replication in a kinase-dependent manner with concomitant increase of eIF2alpha phosphorylation |
| GO:0045071 negative regulation of viral genome replication | IMP PMID:19840259 Double-stranded RNA-activated protein kinase inhibits hepati... | ACCEPT | Summary: IMP: stable PKR knockdown increased HCV subgenomic replicon replication. Reason: Consistent human evidence. Supporting Evidence: PMID:19840259 In stable PKR knockdown cells that harboured a subgenomic replicon, luciferase activity was approximately three times higher than that of control cells |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:15121867 TRAF family proteins link PKR with NF-kappa B activation. | KEEP AS NON CORE | Summary: IDA: PKR colocalizes with TRAFs, including in the perinuclear region, by confocal microscopy. Reason: A subcytoplasmic distribution observed in one imaging study. True but peripheral. Supporting Evidence: PMID:15121867 we present evidence of the colocalization and physical interaction between PKR and TRAF family proteins in vivo, as shown by immunoprecipitation and confocal microscopy experiments file:human/EIF2AK2/EIF2AK2-uniprot.txt Cytoplasm, perinuclear region |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA from UniProt subcellular location (perinuclear region). Reason: As for the IDA row; peripheral. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt Cytoplasm, perinuclear region |
| GO:0051607 defense response to virus | IEP PMID:32634389 Chikungunya virus infection induces differential inflammator... | ACCEPT | Summary: IEP: PKR mRNA induced by chikungunya virus infection of monocytes and macrophages. Reason: Expression evidence alone is weak, but the claim that PKR acts in defence against viruses is well established (PMID:19189853), so the term is accepted. Supporting Evidence: PMID:32634389 double-stranded RNA-activated protein kinase R (PKR) mRNA levels were detected in response to CHIKV infection of monocytes and MDMs PMID:19189853 transient expression of PKR inhibited HCV replication in a kinase-dependent manner with concomitant increase of eIF2alpha phosphorylation |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-mapped IEA for protein serine kinase activity. Reason: PKR phosphorylates eIF2alpha on Ser51 and other serine substrates. Correct. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection |
| GO:0140374 antiviral innate immune response | IDA PMID:22948139 Protein kinase PKR amplification of interferon Ξ² induction o... | ACCEPT | Summary: IDA: PKR amplifies IFN-beta induction through eIF2alpha-dependent translational control. Reason: Core immune role of PKR. Supporting Evidence: PMID:22948139 These results suggest that an eIF-2Ξ±-dependent translation inhibition mechanism is sufficient to explain the PKR-mediated amplification of IPS-1-dependent IFN-Ξ² induction by foreign RNA |
| GO:1900225 regulation of NLRP3 inflammasome complex assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA from mouse Pkr for regulation of NLRP3 inflammasome complex assembly. Reason: PKR-deficient macrophages showed impaired inflammasome activation, and PKR physically associated with inflammasome components. Later work from other groups has questioned whether PKR is required, so the role is kept as non-core. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes PMID:22801494 Collectively, these findings establish a critical role for PKR in activating the NLRP3 inflammasome |
| GO:1900225 regulation of NLRP3 inflammasome complex assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Pkr for regulation of NLRP3 inflammasome complex assembly. Reason: As for the IEA row. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from mouse Pkr: positive regulation of non-canonical NF-kappaB signalling. Reason: This term was transferred from mouse Pkr. It is a downstream or context-specific signalling role, reported from mouse models, not the core eIF2alpha kinase function. It is kept as non-core. Most human data concern canonical (IKK/TRAF) NF-kappaB activation. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt 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 |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred from mouse Pkr: positive regulation of non-canonical NF-kappaB signalling. Reason: This term was transferred from mouse Pkr. It is a downstream or context-specific signalling role, reported from mouse models, not the core eIF2alpha kinase function. It is kept as non-core. Most human data concern canonical (IKK/TRAF) NF-kappaB activation. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt 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 |
| GO:1901532 regulation of hematopoietic progenitor cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from mouse Pkr: regulation of hematopoietic progenitor cell differentiation. Reason: This term was transferred from mouse Pkr. It is a downstream or context-specific signalling role, reported from mouse models, not the core eIF2alpha kinase function. It is kept as non-core. PKR stress signalling affects haematopoietic stem and progenitor cells, for example in Fanconi anemia, where PKR is hyperactive. Supporting Evidence: PMID:12882984 Lymphoblasts from patients with Fanconi anemia (FA) expressed low levels of NPM, which correlated with high ground-state activation of PKR and cellular hypersensitivity to apoptotic cues |
| GO:1901532 regulation of hematopoietic progenitor cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred from mouse Pkr: regulation of hematopoietic progenitor cell differentiation. Reason: This term was transferred from mouse Pkr. It is a downstream or context-specific signalling role, reported from mouse models, not the core eIF2alpha kinase function. It is kept as non-core. PKR stress signalling affects haematopoietic stem and progenitor cells, for example in Fanconi anemia, where PKR is hyperactive. Supporting Evidence: PMID:12882984 Lymphoblasts from patients with Fanconi anemia (FA) expressed low levels of NPM, which correlated with high ground-state activation of PKR and cellular hypersensitivity to apoptotic cues |
| GO:1902033 regulation of hematopoietic stem cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from mouse Pkr: regulation of hematopoietic stem cell proliferation. Reason: This term was transferred from mouse Pkr. It is a downstream or context-specific signalling role, reported from mouse models, not the core eIF2alpha kinase function. It is kept as non-core. PKR stress signalling affects haematopoietic stem and progenitor cells, for example in Fanconi anemia, where PKR is hyperactive. Supporting Evidence: PMID:12882984 Lymphoblasts from patients with Fanconi anemia (FA) expressed low levels of NPM, which correlated with high ground-state activation of PKR and cellular hypersensitivity to apoptotic cues |
| GO:1902033 regulation of hematopoietic stem cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred from mouse Pkr: regulation of hematopoietic stem cell proliferation. Reason: This term was transferred from mouse Pkr. It is a downstream or context-specific signalling role, reported from mouse models, not the core eIF2alpha kinase function. It is kept as non-core. PKR stress signalling affects haematopoietic stem and progenitor cells, for example in Fanconi anemia, where PKR is hyperactive. Supporting Evidence: PMID:12882984 Lymphoblasts from patients with Fanconi anemia (FA) expressed low levels of NPM, which correlated with high ground-state activation of PKR and cellular hypersensitivity to apoptotic cues |
| GO:1902036 regulation of hematopoietic stem cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transferred from mouse Pkr: regulation of hematopoietic stem cell differentiation. Reason: This term was transferred from mouse Pkr. It is a downstream or context-specific signalling role, reported from mouse models, not the core eIF2alpha kinase function. It is kept as non-core. PKR stress signalling affects haematopoietic stem and progenitor cells, for example in Fanconi anemia, where PKR is hyperactive. Supporting Evidence: PMID:12882984 Lymphoblasts from patients with Fanconi anemia (FA) expressed low levels of NPM, which correlated with high ground-state activation of PKR and cellular hypersensitivity to apoptotic cues |
| GO:1902036 regulation of hematopoietic stem cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Transferred from mouse Pkr: regulation of hematopoietic stem cell differentiation. Reason: This term was transferred from mouse Pkr. It is a downstream or context-specific signalling role, reported from mouse models, not the core eIF2alpha kinase function. It is kept as non-core. PKR stress signalling affects haematopoietic stem and progenitor cells, for example in Fanconi anemia, where PKR is hyperactive. Supporting Evidence: PMID:12882984 Lymphoblasts from patients with Fanconi anemia (FA) expressed low levels of NPM, which correlated with high ground-state activation of PKR and cellular hypersensitivity to apoptotic cues |
| GO:2000766 negative regulation of cytoplasmic translation | IDA PMID:12882984 Nucleophosmin interacts with and inhibits the catalytic func... | ACCEPT | Summary: IDA: overexpression of the PKR inhibitor NPM suppressed PKR activity and enhanced protein synthesis. Reason: Core outcome: activated PKR represses cytoplasmic translation through eIF2alpha phosphorylation. Supporting Evidence: PMID:12882984 overexpression of NPM suppressed PKR activity, enhanced protein synthesis, and inhibited apoptosis PMID:1695551 On activation by dsRNA in the presence of ATP, the kinase becomes autophosphorylated and can catalyze the phosphorylation of the alpha subunit of eIF2, which leads to an inhibition of the initiation of protein synthesis |
| GO:2000766 negative regulation of cytoplasmic translation | IMP PMID:19189853 PKR protein kinase is activated by hepatitis C virus and inh... | ACCEPT | Summary: IMP: PKR inhibits HCV protein translation via eIF2alpha phosphorylation. Reason: Core. Supporting Evidence: PMID:19189853 PKR is activated by HCV infection and plays a critical antiviral role through inhibition of viral protein translation |
| GO:0140467 integrated stress response signaling | IC PMID:19189853 PKR protein kinase is activated by hepatitis C virus and inh... | NEW | Summary: Proposed: PKR is the dsRNA-activated eIF2alpha kinase branch of the integrated stress response. Reason: PKR performs the initiating step of ISR signalling, eIF2alpha Ser51 phosphorylation, in response to dsRNA. Comparator check: the paralogous ISR kinase EIF2AK1/HRI carries this term (IDA), and PKR performs the same eIF2alpha Ser51 phosphorylation step as HRI, so it stands in the same role relative to the process. The term is not an ancestor or descendant of other terms the gene carries. Supporting Evidence: file:human/EIF2AK2/EIF2AK2-uniprot.txt Inhibits viral replication via the integrated stress response (ISR) PMID:19189853 transient expression of PKR inhibited HCV replication in a kinase-dependent manner with concomitant increase of eIF2alpha phosphorylation PMID:1695551 On activation by dsRNA in the presence of ATP, the kinase becomes autophosphorylated and can catalyze the phosphorylation of the alpha subunit of eIF2, which leads to an inhibition of the initiation of protein synthesis |
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Download this section (compressed HTML)Q: Is PKR required for NLRP3 inflammasome activation in human macrophages? The mouse knockout data are conflicting, and the NLRP3 regulation rows depend on them.
Q: Which of the many reported non-eIF2alpha substrates (MKK6, PPP2R5A, ILF3, TP53, CDK1, MAPT, SNCA) are phosphorylated by endogenous PKR at physiological levels?
Q: Should the IMP rows from PMID:25329545 (eIF2alpha kinase activity; cellular response to amino acid starvation) be checked against the full text? The abstract foregrounds PERK and GCN2.
Experiment: Use phosphoproteomics in PKR-knockout versus kinase-dead knock-in human cells after dsRNA transfection to identify which secondary substrates depend on endogenous PKR activity, separate from the effects of eIF2alpha phosphorylation.
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