InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: EIF2AK2

Summary

InnateDB Gene

IDBG-44867.6

Last Modified

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

Gene Symbol

EIF2AK2

Gene Name

eukaryotic translation initiation factor 2-alpha kinase 2

Synonyms

EIF2AK1; PKR; PPP1R83; PRKR

Species

Homo sapiens

Ensembl Gene

ENSG00000055332

Encoded Proteins

IDBP-44871

eukaryotic translation initiation factor 2-alpha kinase 2

IDBP-64486

eukaryotic translation initiation factor 2-alpha kinase 2

IDBP-240183

eukaryotic translation initiation factor 2-alpha kinase 2

IDBP-294053

eukaryotic translation initiation factor 2-alpha kinase 2

IDBP-372514

eukaryotic translation initiation factor 2-alpha kinase 2

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 12954221

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

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

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

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

PMID 22912779

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

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

PMID 23236554

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

PMID 23372823

EIF2AK2 binds to dsRNA to inhibit IFN induction triggered by dengue virus.

PMID 25520508

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

InnateDB Annotation from Orthologs

Summary

PMID 22912779

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

PMID 23115300

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

Entrez Gene

Summary

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 2:37099210-37157065

Strand

Reverse strand

Band

p22.2

Transcripts

ENST00000233057	ENSP00000233057
ENST00000390013	ENSP00000374663
ENST00000395127	ENSP00000378559
ENST00000405334	ENSP00000385014
ENST00000411537	ENSP00000393921
ENST00000462861
ENST00000496059

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 134 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	134 [view]
Protein-Protein	120 [view]
Protein-DNA	10 [view]
Protein-RNA	2 [view]
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [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:0004694	eukaryotic translation initiation factor 2alpha 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:0008601	protein phosphatase type 2A regulator activity
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:0008285	negative regulation of cell proliferation
GO:0009615	response to virus
GO:0017148	negative regulation of translation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0019048	modulation by virus of host morphology or physiology
GO:0019054	modulation by virus of host process
GO:0019058	viral life cycle
GO:0030683	evasion or tolerance by virus of host immune response
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

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0016020	membrane
GO:0048471	perinuclear region of cytoplasm

Orthologs

Species

Mus musculus

Bos taurus

Gene ID

Gene Order

ENSMUSG00000024079

View Gene Order

ENSBTAG00000008703

Not yet available

Pathways

NETPATH

REACTOME

REACT_115831

ISG15 antiviral mechanism pathway

REACT_6350

Inhibition of PKR pathway

REACT_6167

Influenza Infection pathway

REACT_115676

Antiviral mechanism by IFN-stimulated genes pathway

REACT_75790

Cytokine Signaling in Immune system pathway

REACT_6222

NS1 Mediated Effects on Host Pathways pathway

REACT_25229

Interferon Signaling pathway

REACT_6900

Immune System pathway

REACT_6323

Host Interactions with Influenza Factors pathway

REACT_116125

Disease pathway

KEGG

hsa04141

Protein processing in endoplasmic reticulum pathway

hsa05160

Hepatitis C pathway

INOH

PID NCI

ceramide_pathway

Ceramide signaling pathway

tcptp_pathway

Signaling events mediated by TCPTP

pdgfrbpathway

PDGFR-beta signaling pathway

Cross-References

SwissProt

P19525

TrEMBL

C9JZT2 F8WBH4

UniProt Splice Variant

Entrez Gene

5610

UniGene

Hs.131431 Hs.593649 Hs.595864 Hs.733265 Hs.738069

RefSeq

NM_001135652 NM_001135651 NM_002759

HUGO

HGNC:9437

OMIM

176871

CCDS

CCDS46259 CCDS1786

HPRD

01468

IMGT

EMBL

AC007899 AF167460 AF167462 AF167463 AF167464 AF167465 AF167466 AF167468 AF167470 AF167472 AK290655 AK313818 AY228338 AY302136 BC093676 BC101475 CH471053 M35663 M85294 U50634 U50635 U50636 U50637 U50638 U50639 U50640 U50641 U50642 U50643 U50644 U50645 U50646 U50647 U50648

GenPept

AAA18253 AAA36409 AAC50768 AAF13156 AAH93676 AAI01476 AAO38055 AAP57628 AAY24317 BAF83344 BAG36554 EAX00407 EAX00408 EAX00409

RNA Seq Atlas

5610