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EIF2AK2 eukaryotic translation initiation factor 2 alpha kinase 2 [ Homo sapiens (human) ]

Gene ID: 5610, updated on 1-Aug-2020

Summary

Official Symbol
EIF2AK2provided by HGNC
Official Full Name
eukaryotic translation initiation factor 2 alpha kinase 2provided by HGNC
Primary source
HGNC:HGNC:9437
See related
Ensembl:ENSG00000055332 MIM:176871
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PKR; PRKR; LEUDEN; EIF2AK1; PPP1R83
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]
Expression
Ubiquitous expression in bone marrow (RPKM 8.7), brain (RPKM 6.4) and 25 other tissues See more
Orthologs

Genomic context

See EIF2AK2 in Genome Data Viewer
Location:
2p22.2
Exon count:
17
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (37099210..37157065, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (37332281..37384190, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene striatin Neighboring gene RNA, U6 small nuclear 577, pseudogene Neighboring gene HEAT repeat containing 5B Neighboring gene G-patch domain containing 11 Neighboring gene ARL14EP pseudogene 1 Neighboring gene sulfotransferase family 6B member 1 Neighboring gene ribosomal protein L31 pseudogene 16 Neighboring gene CEBPZ opposite strand Neighboring gene CCAAT enhancer binding protein zeta

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Overexpression of ADAR1 increases the levels of gp120, p24, and Nef in HIV-1 producer cells, which requires inhibition of the RNA-activated protein kinase PKR PubMed
env Inactivation of PKR has an inhibitory effect on gp120-induced caspase-3 activation PubMed
env HIV-1 gp120 induces activation of PKR and its translocation from cytoplasm to nucleus in neuronal cell lines PubMed
Envelope surface glycoprotein gp160, precursor env Activation of PKR decreases HIV-1 Env expression and knockdown of PKR expression increases intracellular HIV-1 Env expression in human and murine cell lines PubMed
Nef nef The small molecule PKR inhibitor C16 inhibits the IFITM3-induced suppression of HIV-1 Gag, Vif, and Nef protein expression PubMed
nef Overexpression of ADAR1 increases the levels of gp120, p24, and Nef in HIV-1 producer cells, which requires inhibition of the RNA-activated protein kinase PKR PubMed
Pr55(Gag) gag The small molecule PKR inhibitor C16 inhibits the IFITM3-induced suppression of HIV-1 Gag, Vif, and Nef protein expression PubMed
gag HIV-1 Gag is identified to have a physical interaction with eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
Tat tat HIV-1 Tat, specifically amino acids 49-57, increases activation of PKR in Leishmania-infected macrophages PubMed
tat HIV-1 Tat increases expression of EIF2AK2 (PKR) in Leishmania-infected macrophages PubMed
tat PKR directly interacts with HIV-1 Tat and phosphorylates the first exon of Tat exclusively at five Ser/Thr residues (T23, T40, S46, S62, and S68), which inhibits Tat-mediated provirus transcription PubMed
tat PKR-mediated Tat phosphorylation inhibits Tat nuclear localization, and disrupts Tat binding to HIV-1 TAR RNA and interaction with cyclin T1 in HeLa cells PubMed
tat Mutations in HIV-1 Tat that prevent Tat phosphorylation by PKR result in an up to 4-fold decrease in HIV-1 LTR transactivation by Tat PubMed
tat HIV-1 Tat-induction of IL-10 dysregulation is associated with PKR activation in primary blood monocytes PubMed
tat Microarray analysis indicates HIV-1 Tat upregulates the interferon-responsive gene expression of many proteins, including PKR, in immature dendritic cells, an effect that likely facilitates the expansion of HIV-1 infection PubMed
tat PKR enhances HIV-1 Tat-mediated activation of NF-kappaB activation and transcriptional induction of the HIV-1 LTR promoter in the murine HL3T1 cell line PubMed
tat HIV-1 Tat downregulates the steady-state amount of p68 kinase (PKR) in interferon-treated HeLa cells stably expressing Tat PubMed
tat HIV-1 Tat inhibits the activation, activity and autophosphorylation of PKR, suggesting a potential mechanism by which HIV could suppress the interferon system PubMed
tat Binding of HIV-1 Tat to PKR has been mapped to residues 40-58 of Tat, overlapping the hydrophobic core and basic region of Tat PubMed
tat HIV-1 Tat is phosphorylated by PKR on serine 62, threonine 64 and serine 68 PubMed
tat HIV-1 Tat interacts with interferon-inducible enzymes 2-5A synthetase and dsRNA-dependent protein kinase to influence the rate of translation and protein synthesis in vitro PubMed
Vif vif The small molecule PKR inhibitor C16 inhibits the IFITM3-induced suppression of HIV-1 Gag, Vif, and Nef protein expression PubMed
Vpu vpu The expression of eukaryotic translation initiation factor 2-alpha kinase 2 is enhanced in Vpu-deficient HIV-1-infected cells as compared to that in wild-type-infected cells PubMed
capsid gag Overexpression of ADAR1 increases the levels of gp120, p24, and Nef in HIV-1 producer cells, which requires inhibition of the RNA-activated protein kinase PKR PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC126524

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
RNA binding HDA PubMed 
double-stranded RNA binding IDA
Inferred from Direct Assay
more info
PubMed 
eukaryotic translation initiation factor 2alpha kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
eukaryotic translation initiation factor 2alpha kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
non-membrane spanning protein tyrosine kinase activity IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein phosphatase regulator activity TAS
Traceable Author Statement
more info
PubMed 
protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
activation of MAPKK activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to amino acid starvation IMP
Inferred from Mutant Phenotype
more info
PubMed 
defense response to virus IEA
Inferred from Electronic Annotation
more info
 
endoplasmic reticulum unfolded protein response IEA
Inferred from Electronic Annotation
more info
 
evasion or tolerance by virus of host immune response TAS
Traceable Author Statement
more info
 
innate immune response IEA
Inferred from Electronic Annotation
more info
 
negative regulation of apoptotic process IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cell proliferation TAS
Traceable Author Statement
more info
PubMed 
negative regulation of osteoblast proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of translation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of translation IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of viral genome replication IMP
Inferred from Mutant Phenotype
more info
PubMed 
peptidyl-tyrosine phosphorylation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of NIK/NF-kappaB signaling ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of chemokine production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of cytokine production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of stress-activated MAPK cascade ISS
Inferred from Sequence or Structural Similarity
more info
 
protein autophosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
protein autophosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of NLRP3 inflammasome complex assembly ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of hematopoietic progenitor cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of hematopoietic stem cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of hematopoietic stem cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of phosphoprotein phosphatase activity IEA
Inferred from Electronic Annotation
more info
 
regulation of translational initiation by eIF2 alpha phosphorylation IEA
Inferred from Electronic Annotation
more info
 
response to interferon-alpha IDA
Inferred from Direct Assay
more info
PubMed 
response to virus IMP
Inferred from Mutant Phenotype
more info
PubMed 
translation IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
cytosolic ribosome IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
membrane HDA PubMed 
nucleus IEA
Inferred from Electronic Annotation
more info
 
perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
ribosome TAS
Traceable Author Statement
more info
PubMed 

General protein information

Preferred Names
interferon-induced, double-stranded RNA-activated protein kinase
Names
P1/eIF-2A protein kinase
double stranded RNA activated protein kinase
eIF-2A protein kinase 2
interferon-inducible elF2alpha kinase
p68 kinase
protein kinase R
protein kinase, interferon-inducible double stranded RNA dependent
protein phosphatase 1, regulatory subunit 83
tyrosine-protein kinase EIF2AK2
NP_001129123.1
NP_001129124.1
NP_002750.1
XP_011531289.1
XP_016859992.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_030351.1 RefSeqGene

    Range
    5001..56910
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001135651.3NP_001129123.1  interferon-induced, double-stranded RNA-activated protein kinase isoform a

    See identical proteins and their annotated locations for NP_001129123.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses a different splice site in the 5' UTR, compared to variant 1. Variants 1 and 2 both encode the same protein (isoform a).
    Source sequence(s)
    AC007899, BC040851, BU687340
    Consensus CDS
    CCDS1786.1
    UniProtKB/Swiss-Prot
    P19525
    UniProtKB/TrEMBL
    Q8IW76
    Related
    ENSP00000233057.4, ENST00000233057.9
    Conserved Domains (2) summary
    smart00358
    Location:101166
    DSRM; Double-stranded RNA binding motif
    cd14047
    Location:260536
    STKc_EIF2AK2_PKR; Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA
  2. NM_001135652.2NP_001129124.1  interferon-induced, double-stranded RNA-activated protein kinase isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a. The 5' UTR splice pattern of this transcript has not been determined.
    Source sequence(s)
    AC007899, BC101475, BU687340
    Consensus CDS
    CCDS46259.1
    UniProtKB/Swiss-Prot
    P19525
    Related
    ENSP00000385014.1, ENST00000405334.5
    Conserved Domains (3) summary
    smart00220
    Location:252493
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    smart00358
    Location:101166
    DSRM; Double-stranded RNA binding motif
    cl21453
    Location:262495
    PKc_like; Protein Kinases, catalytic domain
  3. NM_002759.3NP_002750.1  interferon-induced, double-stranded RNA-activated protein kinase isoform a

    See identical proteins and their annotated locations for NP_002750.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. Variants 1 and 2 both encode the same protein (isoform a).
    Source sequence(s)
    AC007899, BC040851, BU687340
    Consensus CDS
    CCDS1786.1
    UniProtKB/Swiss-Prot
    P19525
    UniProtKB/TrEMBL
    Q8IW76
    Related
    ENSP00000378559.2, ENST00000395127.6
    Conserved Domains (2) summary
    smart00358
    Location:101166
    DSRM; Double-stranded RNA binding motif
    cd14047
    Location:260536
    STKc_EIF2AK2_PKR; Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20200522

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

    Range
    37099210..37157065 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011532987.2XP_011531289.1  interferon-induced, double-stranded RNA-activated protein kinase isoform X1

    See identical proteins and their annotated locations for XP_011531289.1

    UniProtKB/Swiss-Prot
    P19525
    Conserved Domains (2) summary
    smart00358
    Location:101166
    DSRM; Double-stranded RNA binding motif
    cd14047
    Location:260536
    STKc_EIF2AK2_PKR; Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA
  2. XM_017004503.1XP_016859992.1  interferon-induced, double-stranded RNA-activated protein kinase isoform X2

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