eukaryotic translation initiation factor 2 alpha kinase 2 | Other PEK family kinases | IUPHAR Guide to IMMUNOPHARMACOLOGY

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eukaryotic translation initiation factor 2 alpha kinase 2

  Target has curated data in GtoImmuPdb

Target id: 2016

Nomenclature: eukaryotic translation initiation factor 2 alpha kinase 2

Abbreviated Name: PKR

Family: Other PEK family kinases

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 551 2p22-p21 EIF2AK2 eukaryotic translation initiation factor 2 alpha kinase 2
Mouse - 515 17 E2 Eif2ak2 eukaryotic translation initiation factor 2-alpha kinase 2
Rat - 513 6q 11 Eif2ak2 eukaryotic translation initiation factor 2-alpha kinase 2
Previous and Unofficial Names
protein kinase R (PKR) | EIF2AK1 | IFN-induced and double-stranded RNA-activated kinase | P1/eIF-2A protein kinase | p68 kinase | protein kinase RNA-activated
Database Links
BRENDA
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  PKR kinase domain- eIF2alpha- AMP-PNP complex.
PDB Id:  2A19
Resolution:  2.5Å
Species:  Human
References:  2
Enzyme Reaction
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Parameter Reference
indirubin derivative E804 Hs Inhibition >7.0 pIC50 1
pIC50 >7.0 (IC50 <1x10-7 M) [1]
PKR inhibitor Hs Inhibition 6.7 pIC50 5
pIC50 6.7 (IC50 2.1x10-7 M) [5]
Cdk2 inhibitor IV Hs Inhibition 5.7 pIC50 1
pIC50 5.7 (IC50 2x10-6 M) [1]
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 3,6

Key to terms and symbols Click column headers to sort
Target used in screen: PRKR
Ligand Sp. Type Action Affinity Parameter
lestaurtinib Hs Inhibitor Inhibition 6.9 pKd
tamatinib Hs Inhibitor Inhibition 6.7 pKd
staurosporine Hs Inhibitor Inhibition 6.4 pKd
BI-2536 Hs Inhibitor Inhibition 6.3 pKd
sunitinib Hs Inhibitor Inhibition 6.2 pKd
CHIR-265 Hs Inhibitor Inhibition 6.0 pKd
AST-487 Hs Inhibitor Inhibition 6.0 pKd
crizotinib Hs Inhibitor Inhibition 6.0 pKd
fedratinib Hs Inhibitor Inhibition 6.0 pKd
SU-14813 Hs Inhibitor Inhibition 5.9 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
Protein kinase-R (EIF2AK2) is activated by virally-introduced double-stranded RNA (dsRNA), and is therefore involved in protection against viral infection. Protein activator of the interferon-induced protein kinase EIF2AK2 (PACT; PRKRA) also activates protein kinase-R. Activated protein kinase-R phosphorylates the eukaryotic translation initiation factor eIF2α inhibiting viral protein synthesis [4]. Protein kinase-R signalling to the NF-κB pathway upregulates the expression of interferons to amplify and spread the immune response.
Immuno Process Associations
Immuno Process:  Immune regulation
GO Annotations:  Associated to 3 GO processes
GO:1901532 regulation of hematopoietic progenitor cell differentiation ISS
GO:1902033 regulation of hematopoietic stem cell proliferation ISS
GO:1902036 regulation of hematopoietic stem cell differentiation ISS
Immuno Process:  Immune system development
GO Annotations:  Associated to 3 GO processes
GO:1901532 regulation of hematopoietic progenitor cell differentiation ISS
GO:1902033 regulation of hematopoietic stem cell proliferation ISS
GO:1902036 regulation of hematopoietic stem cell differentiation ISS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 3 GO processes
GO:0001819 positive regulation of cytokine production ISS
GO:0032722 positive regulation of chemokine production ISS
GO:0035455 response to interferon-alpha IDA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0032722 positive regulation of chemokine production ISS
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0045087 innate immune response IEA

References

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1. Bryk R, Wu K, Raimundo BC, Boardman PE, Chao P, Conn GL, Anderson E, Cole JL, Duffy NP, Nathan C et al.. (2011) Identification of new inhibitors of protein kinase R guided by statistical modeling. Bioorg. Med. Chem. Lett., 21 (13): 4108-14. [PMID:21632247]

2. Dar AC, Dever TE, Sicheri F. (2005) Higher-order substrate recognition of eIF2alpha by the RNA-dependent protein kinase PKR. Cell, 122 (6): 887-900. [PMID:16179258]

3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]

4. García MA, Gil J, Ventoso I, Guerra S, Domingo E, Rivas C, Esteban M. (2006) Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action. Microbiol. Mol. Biol. Rev., 70 (4): 1032-60. [PMID:17158706]

5. Jammi NV, Whitby LR, Beal PA. (2003) Small molecule inhibitors of the RNA-dependent protein kinase. Biochem. Biophys. Res. Commun., 308 (1): 50-7. [PMID:12890478]

6. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol., 17 (11): 1241-9. [PMID:21095574]

How to cite this page

Other PEK family kinases: eukaryotic translation initiation factor 2 alpha kinase 2. Last modified on 15/02/2017. Accessed on 23/03/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2016.