Relation Results

Identifier	Residue	Sequence	Organism
SIGNOR-278514	Ser225	VGSKTPAsPVVVQQG	Homo sapiens
pmid	sentence
32801355	This suggests that PKR is critical in the phosphorylation of SPHK1 at Ser225.\|We confirmed that phosphorylated PKR activates SPHK1 kinase activity, but it remained necessary to determine whether there has mutual correlation or any reciprocal effect between these two kinases in stressed cells.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence	Organism
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
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
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
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
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
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
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

Identifier	Residue	Sequence	Organism
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

Identifier	Residue	Sequence	Organism
SIGNOR-278310	Ser312	TESITATsPASMVGG	Homo sapiens
pmid	sentence
20685959	First, PKR induces phosphorylation of IRS1 at Ser312 and suppresses tyrosine phosphorylation of IRS1, mediated by the insulin receptor substrates kinases, JNK and I\u03baB kinase.\|These results suggest that PKR induces the inhibitory phosphorylation of IRS1 at Ser312 in HepG2 cells, thereby suppressing the phosphorylation at Tyr941.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Sequence
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

Identifier	Residue	Sequence	Organism
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

Identifier	Residue	Sequence	Organism
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

Identifier	Residue	Sequence	Organism
SIGNOR-279612	Ser727	NTIDLPMsPRTLDSL	Homo sapiens
pmid	sentence
25360179	Silencing PKR gene expression in HepG2 cells with siRNA reduced STAT3 phosphorylation at Tyr705 and Ser727 (XREF_FIG).\|The results also revealed that PKR activates STAT3, a transcription factor associated with primary liver tumors, which is suggested to promote tumor cell proliferation.

Identifier	Residue	Sequence	Organism
SIGNOR-279613	Tyr705	DPGSAAPyLKTKFIC	Homo sapiens
pmid	sentence
25360179	Silencing PKR gene expression in HepG2 cells with siRNA reduced STAT3 phosphorylation at Tyr705 and Ser727 (XREF_FIG).\|The results also revealed that PKR activates STAT3, a transcription factor associated with primary liver tumors, which is suggested to promote tumor cell proliferation.

Publications:

2

Organism:

Homo Sapiens

Pathways:

SARS-CoV CYTOKINE STORM

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

Identifier	Residue	Sequence	Organism
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-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
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-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
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
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

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

Identifier	Residue	Sequence	Organism
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

Identifier	Residue	Sequence	Organism
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

Identifier	Residue	Organism
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

Identifier	Residue	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

Identifier	Residue	Organism
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

Identifier	Residue	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	Organism
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

Identifier	Residue	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

Identifier	Residue	Organism
SIGNOR-279039		Homo sapiens
pmid	sentence
18835251	In these assays, we observed that GST\u2013Nck-1 was clearly phosphorylated by GST\u2013PKR while GST was not ( Fig. 4 , upper panels).

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-279170		Homo sapiens
pmid	sentence
16631606	Ebp1 itself is phosphorylated by the PKR protein kinase, suggesting that the effects of Ebp1 overexpression evidenced in vivo on eIF2alpha phosphorylation could be achieved by competition between Ebp1 and eIF2alpha for PKR kinase activity.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	Organism
SIGNOR-260168		Homo sapiens
pmid	sentence
31226023	Besides PERK, eIF2Î± 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 eIF2Î± 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

Identifier	Residue	Organism
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

Identifier	Residue	Organism
SIGNOR-279707		Homo sapiens
pmid	sentence
15229216	Consistent with this observation, PKR was capable of activating MKK6 as assessed in a coupled kinase assay containing the components of the p38 MAPK pathway.\|In vitro kinase assays revealed that MKK6 was efficiently phosphorylated by PKR, and this could be inhibited by 2-aminopurine.

Publications:

1

Organism:

Homo Sapiens

Pathways:

COVID-19 Causal Network

Identifier	Residue	Organism
SIGNOR-279735		Homo sapiens
pmid	sentence
32716602	Interestingly, PKR phosphorylated tau directly and no detectable labeling occurred when tau was incubated with 32 P\u2010ATP alone (Figure\u00a0 xref right).\|PKR kinase directly regulates tau expression and Alzheimer's disease-related tau phosphorylation.

Publications:

1

Organism:

Homo Sapiens

Identifier	Residue	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

Identifier	Residue	Organism
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

Identifier	Residue	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

Identifier	Residue	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

Identifier	Residue	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

Name	EIF2AK2 View Modifications
Full Name	Interferon-induced, double-stranded RNA-activated protein kinase
Synonyms	Eukaryotic translation initiation factor 2-alpha kinase 2, eIF-2A protein kinase 2, Interferon-inducible RNA-dependent protein kinase, P1/eIF-2A protein kinase, Protein kinase RNA-activated, PKR, Protein kinase R, Tyrosine-protein kinase EIF2AK2, 2.7.10.2, p68 kinase \| PKR, PRKR
Primary ID	P19525
Links	- -
Type	protein
Relations	44
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
Function	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 (PubMed:18835251, PubMed:19507191, PubMed:19189853, PubMed:21123651, PubMed:21072047, PubMed:22948139, PubMed:23229543, PubMed:22381929). Inhibits viral replication via the integrated stress response (ISR)

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