| + |
EIF2AK2 | up-regulates 
phosphorylation
|
EIF2AK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-85765 |
Ser242 |
NQRKAKRsLAPRFDL |
Homo sapiens |
|
| pmid |
sentence |
| 11152499 |
We previously identified four autophosphorylated amino acids and elucidated their participation in pkr activation.Replacement Of all four of these residues in pkr with alanines did not dramatically affect kinase activity in vitro or in yeast saccharomyces cerevisiae.However, when coupled with mutations of serine 242 and threonines 255 and 258 in the central region, these mutations increased pkr protein expression in mammalian cells, consistent with diminished kinase activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-85769 |
Ser83 |
NKEKKAVsPLLLTTT |
Homo sapiens |
|
| pmid |
sentence |
| 11152499 |
Taken together, these results show that pkr is autophosphorylated on serine 83 and threonines 88, 89, and 90, that this autophosphorylation may enhance kinase activation, and that the inhibition of pkr by hcv e2 is not solely due to duplication of and competition with these autophosphorylation sites. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-85773 |
Thr255 |
DLPDMKEtKYTVDKR |
Homo sapiens |
|
| pmid |
sentence |
| 11152499 |
We previously identified four autophosphorylated amino acids and elucidated their participation in pkr activation.Replacement Of all four of these residues in pkr with alanines did not dramatically affect kinase activity in vitro or in yeast saccharomyces cerevisiae.However, when coupled with mutations of serine 242 and threonines 255 and 258 in the central region, these mutations increased pkr protein expression in mammalian cells, consistent with diminished kinase activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-85777 |
Thr258 |
DMKETKYtVDKRFGM |
Homo sapiens |
|
| pmid |
sentence |
| 11152499 |
We previously identified four autophosphorylated amino acids and elucidated their participation in pkr activation.Replacement Of all four of these residues in pkr with alanines did not dramatically affect kinase activity in vitro or in yeast saccharomyces cerevisiae.However, when coupled with mutations of serine 242 and threonines 255 and 258 in the central region, these mutations increased pkr protein expression in mammalian cells, consistent with diminished kinase activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-85781 |
Thr88 |
AVSPLLLtTTNSSEG |
Homo sapiens |
|
| pmid |
sentence |
| 11152499 |
Taken together, these results show that pkr is autophosphorylated on serine 83 and threonines 88, 89, and 90, that this autophosphorylation may enhance kinase activation, and that the inhibition of pkr by hcv e2 is not solely due to duplication of and competition with these autophosphorylation sites. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-85785 |
Thr89 |
VSPLLLTtTNSSEGL |
Homo sapiens |
|
| pmid |
sentence |
| 11152499 |
Taken together, these results show that pkr is autophosphorylated on serine 83 and threonines 88, 89, and 90, that this autophosphorylation may enhance kinase activation, and that the inhibition of pkr by hcv e2 is not solely due to duplication of and competition with these autophosphorylation sites. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-85789 |
Thr90 |
SPLLLTTtNSSEGLS |
Homo sapiens |
|
| pmid |
sentence |
| 11152499 |
Taken together, these results show that pkr is autophosphorylated on serine 83 and threonines 88, 89, and 90, that this autophosphorylation may enhance kinase activation, and that the inhibition of pkr by hcv e2 is not solely due to duplication of and competition with these autophosphorylation sites. |
|
| Publications: |
7 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Innate Immune Response, Inflammosome Activation, SARS-CoV CYTOKINE STORM, SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV STRESS GRANULES, SARS-CoV ER STRESS |
| + |
EIF2AK2 | up-regulates
phosphorylation
|
PPP2R5A |
0.333 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-181793 |
Ser28 |
VDGFTRKsVRKAQRQ |
Homo sapiens |
|
| pmid |
sentence |
| 18957415 |
Phosphorylation of serine 28 by pkr promotes mitochondrial localization of b56alpha, because wild-type but not mutant s28a b56alpha promoted mitochondrial pp2a activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EIF2AK2 | down-regulates quantity by destabilization 
phosphorylation
|
NFKBIA |
0.515 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249335 |
Ser32 |
LLDDRHDsGLDSMKD |
|
|
| pmid |
sentence |
| 10723127 |
As described for other stimuli, following pIC treatment, PKR phosphorylates the NF-kappa B inhibitor I kappa B alpha at serine 32 before degradation. |
|
| Publications: |
1 |
| Pathways: | COVID-19 Causal Network, SARS-CoV STRESS GRANULES |
| + |
EIF2AK2 | up-regulates
phosphorylation
|
TP53 |
0.552 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-68033 |
Ser392 |
FKTEGPDsD |
Homo sapiens |
|
| pmid |
sentence |
| 10348343 |
The double-stranded rna activated protein kinase pkr physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EIF2AK2 | down-regulates
phosphorylation
|
EIF2S1 |
0.717 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-140656 |
Ser52 |
MILLSELsRRRIRSI |
Homo sapiens |
|
| pmid |
sentence |
| 16179259 |
The antiviral protein kinase pkr inhibits protein synthesis by phosphorylating the translation initiation factor eif2alpha on ser51the protein kinases pkr, hri, perk, and gcn2 specifically phosphorylate ser51 on the _ subunit of the translation initiation factor eif2, a gtp binding protein that delivers the initiator methionyl-trna to the small ribosomal subunit in the first step of translation initiation. Phosphorylation of eif2_ converts eif2 from a substrate to an inhibitor of its gdp-gtp exchange factor eif2b, thereby blocking protein synthesis |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV STRESS GRANULES, SARS-CoV ER STRESS |
| + |
EIF2AK2 | down-regulates quantity by destabilization
phosphorylation
|
KDM4C |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277497 |
Ser918 |
MFDDGSFsRDTFPED |
Homo sapiens |
SW-1573 Cell |
| pmid |
sentence |
| 31888886 |
In the absence of Wnt3a, protein kinase R phosphorylated KDM4C at Ser918, inducing KDM4C ubiquitination and degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EIF2AK2 | up-regulates activity
phosphorylation
|
EIF2AK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251110 |
Thr446 |
LKNDGKRtRSKGTLR |
Saccharomyces cerevisiae |
|
| pmid |
sentence |
| 11337501 |
Trans-autophosphorylation of Thr-446 and Thr-451 by the two kinase moieties in a PKR dimer. autophosphorylation in the activation loop would promote proper alignment of key catalytic residues, or the correct orientation of the two lobes of the PKR kinase domain, required for substrate binding or phosphoryl transfer |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-107511 |
Thr451 |
KRTRSKGtLRYMSPE |
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 11337501 |
Taken together, our findings support the idea that binding of pkr to dsrna increases autophosphorylation in the activation loop of the kinase domain (fig. 9). Because dsrna binding promotes dimerization, this would facilitate trans-autophosphorylation of thr-446 and thr-451 by the two kinase moieties in a pkr dimer |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260782 |
Tyr101 |
EGLSMGNyIGLINRI |
in vitro |
|
| pmid |
sentence |
| 16373505 |
PKR autophosphorylates on Y101, Y162, and Y293 in vitro. Site-specific tyrosine phosphorylation is essential for efficient dsRNA-binding, dimerization, kinase activation and eIF2alpha phosphorylation of PKR. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251112 |
Tyr101 |
EGLSMGNyIGLINRI |
Homo sapiens |
HT-1080 Cell |
| pmid |
sentence |
| 16373505 |
PKR autophosphorylates on Y101, Y162, and Y293. unctional characterization of Y101F and Y162F mutants revealed that phosphorylation at these sites is needed for efficient dsRNA binding and kinase dimerization and activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251113 |
Tyr162 |
QLAAKLAyLQILSEE |
Homo sapiens |
HT-1080 Cell |
| pmid |
sentence |
| 16373505 |
PKR autophosphorylates on Y101, Y162, and Y293. unctional characterization of Y101F and Y162F mutants revealed that phosphorylation at these sites is needed for efficient dsRNA binding and kinase dimerization and activation. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260783 |
Tyr162 |
QLAAKLAyLQILSEE |
in vitro |
|
| pmid |
sentence |
| 16373505 |
PKR autophosphorylates on Y101, Y162, and Y293 in vitro. Site-specific tyrosine phosphorylation is essential for efficient dsRNA-binding, dimerization, kinase activation and eIF2alpha phosphorylation of PKR. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260784 |
Tyr293 |
HRIDGKTyVIKRVKY |
in vitro |
|
| pmid |
sentence |
| 16373505 |
PKR autophosphorylates on Y101, Y162, and Y293 in vitro. Site-specific tyrosine phosphorylation is essential for efficient dsRNA-binding, dimerization, kinase activation and eIF2alpha phosphorylation of PKR. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251114 |
Tyr293 |
HRIDGKTyVIKRVKY |
Homo sapiens |
HT-1080 Cell |
| pmid |
sentence |
| 16373505 |
PKR autophosphorylates on Y101, Y162, and Y293. The introduction of the Y293F mutation causes significant defects in PKR autophosphorylation and eIF2α phosphorylation, providing evidence for a critical function of this phosphorylated residue. |
|
| Publications: |
8 |
Organism: |
Saccharomyces Cerevisiae, Homo Sapiens, In Vitro |
| Pathways: | COVID-19 Causal Network, Innate Immune Response, Inflammosome Activation, SARS-CoV CYTOKINE STORM, SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV STRESS GRANULES, SARS-CoV ER STRESS |
| + |
MAPK1 | up-regulates
phosphorylation
|
EIF2AK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-56337 |
Thr451 |
KRTRSKGtLRYMSPE |
Homo sapiens |
|
| pmid |
sentence |
| 9528799 |
Our results provide strong evidence that dsrna binding is required for dimerization of full-length pkr molecules in vivo, leading to autophosphorylation in the activation loop and stimulation of the eif2alpha kinase function of pkr. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RPS6KA3 | up-regulates
phosphorylation
|
EIF2AK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-154183 |
Thr451 |
KRTRSKGtLRYMSPE |
Homo sapiens |
Skin Cancer Cell |
| pmid |
sentence |
| 17404396 |
Our data indicated that phosphorylation of pkr at thr(451) is mediated through erk2 and rsk2, but not through p38 kinase. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EIF2AK2 | down-regulates
phosphorylation
|
CDK1 |
0.333 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-164809 |
Tyr4 |
yTKIEKIG |
Homo sapiens |
|
| pmid |
sentence |
| 20395957 |
Our findings demonstrate that (i) pkr, ser/thr kinase, phosphorylates its new substrate cdc2 at the tyr 4 residue, (ii) pkr-mediated tyr 4-phosphorylation facilitates cdc2 ubiquitination and proteosomal degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EIF2AK2 | up-regulates activity
binding
|
NLRP3 inflammasome |
0.331 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263119 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22801494 |
Here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. PKR physically interacts with several inflammasome components, including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLRP1, NLR family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Inflammosome Activation, SARS-CoV INFLAMMATORY RESPONSE |
| + |
EIF2AK2 | down-regulates activity
phosphorylation
|
EIF2S1 |
0.717 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260168 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31226023 |
Besides PERK, eIF2α can also be phosphorylated by three other kinases: heme-regulated inhibitor kinase (HRI), general control nonderepressible 2 (GCN2), and PKR. PKR is an interferon-stimulated gene (ISG) activated by binding of double-stranded RNA (dsRNA), a common intermediate during the replication of DNA and RNA viruses. Together, these four eIF2α kinases and their convergent downstream signaling pathways are known as the integrated stress response (ISR) |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV STRESS GRANULES, SARS-CoV ER STRESS |
| + |
G3BP1 | up-regulates activity
binding
|
EIF2AK2 |
0.312 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260981 |
|
|
Homo sapiens |
U2-OS Cell, HeLa Cell |
| pmid |
sentence |
| 25784705 |
PKR directly interacts with G3BP1 through the NTF2-like and PXXP domains of G3BP1. The recruitment of inactive PKR to SGs through this interaction correlates with its activation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260750 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25520508 |
We show that G3BP1 can activate effectors of the innate immune transcriptional program, culminating in enhanced expression of a set of cytokines. We demonstrate that a subset of PKR is recruited to SGs, that close-proximity interactions between G3BP1 and PKR complexes increase in response to stress and PKR activation, that once activated PKR no longer associates with SGs, and that the PXXP domain of G3BP1 is essential for PKR recruitment to SGs and PKR activation in cells. Together, these findings suggest that G3BP1 plays an important role in the recruitment of PKR to SGs and suggest that activation of PKR can take place at the SG. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Innate Immune Response, SARS-CoV STRESS GRANULES |
| + |
Viral_dsRNA | up-regulates 
|
EIF2AK2 |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260167 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31226023 |
PKR is an interferon-stimulated gene (ISG) activated by binding of double-stranded RNA (dsRNA), a common intermediate during the replication of DNA and RNA viruses. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Innate Immune Response, Inflammosome Activation, SARS-CoV STRESS GRANULES, SARS-CoV ER STRESS |
| + |
Uridylate-specific endoribonuclease | down-regulates activity 
|
EIF2AK2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260348 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 28158275 |
Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses. Replication of EndoU-deficient coronaviruses is greatly attenuated in vivo and severely restricted in primary cells even during the early phase of the infection. Collectively our results demonstrate that the coronavirus EndoU efficiently prevents simultaneous activation of host cell dsRNA sensors, such as Mda5, OAS and PKR. It is thus tempting to propose that viral dsRNA represents the natural substrate of the coronavirus EndoU. However, it remains to be determined which kind of viral dsRNA is cleaved by the EndoU or triggers Mda5, OAS, and PKR activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV CYTOKINE STORM, SARS-CoV STRESS GRANULES, SARS-CoV ER STRESS |
| + |
ADARB1 | up-regulates activity
binding
|
EIF2AK2 |
0.47 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266359 |
|
|
Homo sapiens |
JURKAT Cell |
| pmid |
sentence |
| 19605474 |
Both forms of ADAR1 show enhanced interactions with PKR at the peak of HIV infection, suggesting a role for this protein in the regulation of PKR activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
EIF2AK2 | up-regulates
|
Immune_response |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260159 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27712625 |
The activated kinases then phosphorylate the signal transducers and transcription factors STAT1 and STAT2, which form a complex with IRF9 (ISGF3) that enters the nucleus to transactivate promoters of an antiviral gene expression program. Genes that are specifically upregulated by IFNs are collectively called ISGs (IFN-stimulated genes). The kinase PKR is an ISG product acting as a signaling PRR on one hand (see earlier), but its main function in antiviral defense is the inhibition of protein synthesis.PKR has a broad antiviral spectrum. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Innate Immune Response, Inflammosome Activation, SARS-CoV CYTOKINE STORM, SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV STRESS GRANULES |
| + |
EIF2AK2 | up-regulates activity
binding
|
AIM2 inflammasome |
0.319 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263120 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22801494 |
Here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. PKR physically interacts with several inflammasome components, including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLRP1, NLR family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Inflammosome Activation |
| + |
ISGF3 complex | up-regulates quantity by expression
transcriptional regulation
|
EIF2AK2 |
0.491 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260158 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27712625 |
The activated kinases then phosphorylate the signal transducers and transcription factors STAT1 and STAT2, which form a complex with IRF9 (ISGF3) that enters the nucleus to transactivate promoters of an antiviral gene expression program. Genes that are specifically upregulated by IFNs are collectively called ISGs (IFN-stimulated genes). The kinase PKR is an ISG product acting as a signaling PRR on one hand (see earlier), but its main function in antiviral defense is the inhibition of protein synthesis.PKR has a broad antiviral spectrum. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Inflammosome Activation, SARS-CoV CYTOKINE STORM, SARS-CoV INFLAMMATORY RESPONSE |
| + |
EIF2AK2 | up-regulates activity
binding
|
NLRC4 inflammasome |
0.314 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263121 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22801494 |
Here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. PKR physically interacts with several inflammasome components, including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLRP1, NLR family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Inflammosome Activation |
| + |
EIF2AK2 | up-regulates activity
binding
|
NLRP1 inflammasome |
0.307 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263118 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 22801494 |
Here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. PKR physically interacts with several inflammasome components, including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLRP1, NLR family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Inflammosome Activation |
| + |
DNAJC3 | down-regulates activity
binding
|
EIF2AK2 |
0.62 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-246207 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 25329545 |
The protein p58IPK {also known asDnaJ3C [DnaJ heat-shock protein (hsp) 40 homologue, subfamily C, member 3]} is known to inhibit the eIF2 kinases PKR (dsRNA-dependent protein kinase/eIF2 kinase 2) and PERK |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
EIF2AK2
- 
- 