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eukaryotic translation initiation factor 2 alpha kinase 2

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Immunopharmacology Ligand  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

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 551 2p22.2 EIF2AK2 eukaryotic translation initiation factor 2 alpha kinase 2
Mouse - 515 17 49.56 cM Eif2ak2 eukaryotic translation initiation factor 2-alpha kinase 2
Rat - 513 6q11 Eif2ak2 eukaryotic translation initiation factor 2-alpha kinase 2
Previous and Unofficial Names Click here for help
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 Click here for help
Alphafold P19525 (Hs), Q03963 (Mm), Q63184 (Rn)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL5785 (Hs), CHEMBL1795121 (Mm)
Ensembl Gene ENSG00000055332 (Hs), ENSMUSG00000024079 (Mm), ENSRNOG00000048315 (Rn)
Entrez Gene 5610 (Hs), 19106 (Mm), 54287 (Rn)
Human Protein Atlas ENSG00000055332 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:5610 (Hs), mmu:19106 (Mm), rno:54287 (Rn)
OMIM 176871 (Hs)
Pharos P19525 (Hs)
RefSeq Nucleotide NM_001135651 (Hs), NM_011163 (Mm), NM_019335 (Rn)
RefSeq Protein NP_001129123 (Hs), NP_035293 (Mm), NP_062208 (Rn)
UniProtKB P19525 (Hs), Q03963 (Mm), Q63184 (Rn)
Wikipedia EIF2AK2 (Hs)
Selected 3D Structures Click here for help
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 Click here for help
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
indirubin derivative E804 Small molecule or natural product Primary target of this compound Hs Inhibition >7.0 pIC50 1
⤷ pIC50 >7.0 (IC50 <1x10-7 M) [1]
PKR inhibitor Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 6.7 pIC50 5
⤷ pIC50 6.7 (IC50 2.1x10-7 M) [5]
Cdk2 inhibitor IV Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.7 pIC50 1
⤷ pIC50 5.7 (IC50 2x10-6 M) [1]
DiscoveRx KINOMEscan® screen Click here for help
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 Value Parameter
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.9 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.7 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
BI-2536 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
CHIR-265 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.0 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.0 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure 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
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  Inflammation

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 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2016.