InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Gene: Eif2ak2

Summary

InnateDB Gene

IDBG-199014.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Eif2ak2

Gene Name

eukaryotic translation initiation factor 2-alpha kinase 2

Synonyms

2310047A08Rik; 4732414G15Rik; AI467567; AI747578; Pkr; Prkr; Tik

Species

Mus musculus

Ensembl Gene

ENSMUSG00000024079

Encoded Proteins

IDBP-199016

eukaryotic translation initiation factor 2-alpha kinase 2

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 22912779

Antiviral stress granules containing Ddx58 (RIG-I) and Eif2ak2 (PKR) have a critical role in viral detection and innate immunity.

PMID 23115300

Herpes simplex virus evades antiviral host defence by interacting with EIF2AK2 (PKR) to inhibit autophagy.

InnateDB Annotation from Orthologs

Summary

PMID 12954221

[Homo sapiens] EIF2AK2 is a protein kinase that is regulated by RNA and is an important mediator of the antiviral and anti proliferative actions of interferon (IFN).

PMID 12954221

[Homo sapiens] EIF2AK2 binds both SP1 and SP3 but only SP3 functions as part of the interferon-inducible complex with ISGF-3 proteins, consisting of STAT1, STAT2, and IRF9.

PMID 19028691

[Homo sapiens] EIF2AK2 enhances the induction of interferon-beta and apoptosis mediated by cytoplasmic RNA sensors where in addition to MAVS and IRF3 but not TRIF, it is required for maximal type I IFN-beta induction and the induction of apoptosis by both transfected T7 phage polymerase-synthesized RNAs (PRNAs) and polyinosinic-polycytidylic acid.

PMID 20485506

[Homo sapiens] EIF2AK2 is used by hepatitis C virus to restrain its ability to induce IFN through the RIG-I/MAVS pathway.

PMID 22912779

[Homo sapiens] Antiviral stress granules containing DDX58 (RIG-I) and EIF2AK2 (PKR) have a critical role in viral detection and innate immunity. (Demonstrated in mouse)

PMID 23115300

[Homo sapiens] Herpes simplex virus evades antiviral host defence by interacting with EIF2AK2 (PKR) to inhibit autophagy.

PMID 23236554

[Homo sapiens] Bacterial dsRNA or poly(I:C) induces tyrosine phosphorylation of PKR activation by JAK kinases.

PMID 23372823

[Homo sapiens] EIF2AK2 binds to dsRNA to inhibit IFN induction triggered by dengue virus.

PMID 25520508

[Homo sapiens] EIF2AK2 (PKR) is recruited to stress granules by G3BP1 to promote innate immune responses at both transcriptional and translational levels.

Entrez Gene

Summary

This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000055332:
The protein encoded by this gene is a serine/threonine protein kinase that is activated by autophosphorylation after binding to dsRNA. The activated form of the encoded protein can phosphorylate translation initiation factor EIF2S1, which in turn inhibits protein synthesis. This protein is also activated by manganese ions and heparin. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 17:78852564-78882573

Strand

Reverse strand

Band

Transcripts

ENSMUST00000024884	ENSMUSP00000024884
ENSMUST00000169940
ENSMUST00000171852
ENSMUST00000171451

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 5 experimentally validated interaction(s) in this database.
They are also associated with 76 interaction(s) predicted by orthology.

Experimentally validated
Total	5 [view]
Protein-Protein	5 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	76 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003725	double-stranded RNA binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0044822	poly(A) RNA binding

Biological Process

GO:0000186	activation of MAPKK activity
GO:0001819	positive regulation of cytokine production
GO:0006351	transcription, DNA-templated
GO:0006412	translation
GO:0006468	protein phosphorylation
GO:0009615	response to virus
GO:0017148	negative regulation of translation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0030968	endoplasmic reticulum unfolded protein response
GO:0032722	positive regulation of chemokine production
GO:0032874	positive regulation of stress-activated MAPK cascade
GO:0033689	negative regulation of osteoblast proliferation
GO:0035455	response to interferon-alpha
GO:0043066	negative regulation of apoptotic process
GO:0045071	negative regulation of viral genome replication
GO:0045087	innate immune response (InnateDB)
GO:0046777	protein autophosphorylation
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051607	defense response to virus
GO:1900225	regulation of NLRP3 inflammasome complex assembly
GO:1901224	positive regulation of NIK/NF-kappaB signaling
GO:1901532	regulation of hematopoietic progenitor cell differentiation
GO:1902033	regulation of hematopoietic stem cell proliferation
GO:1902036	regulation of hematopoietic stem cell differentiation