Display Settings:

Format

Send to:

Choose Destination

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

Gene ID: 5610, updated on 23-Oct-2014
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; HPRD:01468; 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; 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]
See EIF2AK2 in Epigenomics, MapViewer
Location:
2p22-p21
Exon count:
17
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 2 NC_000002.12 (37105138..37157047, 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 HEAT repeat containing 5B Neighboring gene G patch domain containing 11 Neighboring gene sulfotransferase family, cytosolic, 6B, member 1 Neighboring gene ribosomal protein L31 pseudogene 16 Neighboring gene CEBPZ opposite strand Neighboring gene CCAAT/enhancer binding protein (C/EBP), zeta

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

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 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
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 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 HIV-1 Tat is phosphorylated by PKR on serine 62, threonine 64 and serine 68 PubMed
tat HIV-1 Tat-induction of IL-10 dysregulation is associated with PKR activation in primary blood monocytes 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 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 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
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

  • Antiviral mechanism by IFN-stimulated genes, organism-specific biosystem (from REACTOME)
    Antiviral mechanism by IFN-stimulated genes, organism-specific biosystemThe ISG proteins generated by IFN pathways plays key roles in the induction of innate and adaptive immune responses.
  • Ceramide signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    Ceramide signaling pathway, organism-specific biosystem
    Ceramide signaling pathway
  • Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
    Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Epstein-Barr virus infection, organism-specific biosystem (from KEGG)
    Epstein-Barr virus infection, organism-specific biosystemEpstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is associated with oncogenesis. EBV infection to primary human B lymphocytes leads to induction of EBV-specific HLA-restricted cytotoxi...
  • Epstein-Barr virus infection, conserved biosystem (from KEGG)
    Epstein-Barr virus infection, conserved biosystemEpstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is associated with oncogenesis. EBV infection to primary human B lymphocytes leads to induction of EBV-specific HLA-restricted cytotoxi...
  • Hepatitis C, organism-specific biosystem (from KEGG)
    Hepatitis C, organism-specific biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
  • Hepatitis C, conserved biosystem (from KEGG)
    Hepatitis C, conserved biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
  • Herpes simplex infection, organism-specific biosystem (from KEGG)
    Herpes simplex infection, organism-specific biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • Herpes simplex infection, conserved biosystem (from KEGG)
    Herpes simplex infection, conserved biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • Host Interactions with Influenza Factors, organism-specific biosystem (from REACTOME)
    Host Interactions with Influenza Factors, organism-specific biosystemInfection of a human host cell with influenza virus triggers an array of host processes that interfere with viral replication, notably the production of type I interferon. The viral NS1 protein plays...
  • ISG15 antiviral mechanism, organism-specific biosystem (from REACTOME)
    ISG15 antiviral mechanism, organism-specific biosystemInterferon-stimulated gene 15 (ISG15) is a member of the ubiquitin-like (Ubl) family. It is strongly induced upon exposure to type I Interferons (IFNs), viruses, bacterial LPS, and other stresses. On...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Influenza A, organism-specific biosystem (from KEGG)
    Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
  • Influenza A, conserved biosystem (from KEGG)
    Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
  • Influenza Infection, organism-specific biosystem (from REACTOME)
    Influenza Infection, organism-specific biosystemFor centuries influenza epidemics have plagued man, and influenza was probably the disease described by Hippocrates in 412 BC. Today it remains a major cause of morbidity and mortality worldwide with...
  • Inhibition of PKR, organism-specific biosystem (from REACTOME)
    Inhibition of PKR, organism-specific biosystemThe key role played by PKR in the innate response to virus infection is emphasized by the large number of viruses that encode PKR inhibitors.
  • Integrated Pancreatic Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Pancreatic Cancer Pathway, organism-specific biosystemAn integrated pathway model which displays the protein-protein interactions (PPIs) among the relevant proteins for pancreatic cancer. This pathway is a collection of different mechanistic protein pat...
  • Interferon Signaling, organism-specific biosystem (from REACTOME)
    Interferon Signaling, organism-specific biosystemInterferons (IFNs) are cytokines that play a central role in initiating immune responses, especially antiviral and antitumor effects. There are three types of IFNs:Type I (IFN-alpha, -beta and others...
  • Measles, organism-specific biosystem (from KEGG)
    Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • Measles, conserved biosystem (from KEGG)
    Measles, conserved biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • NS1 Mediated Effects on Host Pathways, organism-specific biosystem (from REACTOME)
    NS1 Mediated Effects on Host Pathways, organism-specific biosystemViral NS1 protein is a nuclear, dimeric protein that is highly expressed in infected cells and has dsRNA-binding activity. The RNA-binding domain lies within the N-terminal portion of the protein. Th...
  • Protein processing in endoplasmic reticulum, organism-specific biosystem (from KEGG)
    Protein processing in endoplasmic reticulum, organism-specific biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
  • Protein processing in endoplasmic reticulum, conserved biosystem (from KEGG)
    Protein processing in endoplasmic reticulum, conserved biosystemThe endoplasmic reticulum (ER) is a subcellular organelle where proteins are folded with the help of lumenal chaperones. Newly synthesized peptides enter the ER via the sec61 pore and are glycosylate...
  • Signaling events mediated by TCPTP, organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by TCPTP, organism-specific biosystem
    Signaling events mediated by TCPTP
  • Translation Factors, organism-specific biosystem (from WikiPathways)
    Translation Factors, organism-specific biosystemProtein synthesis is the ultimate step of gene expression and a key control point for regulation. In particular, it enables cells to rapidly manipulate protein production without new mRNA synthesis, ...
  • Type II interferon signaling (IFNG), organism-specific biosystem (from WikiPathways)
    Type II interferon signaling (IFNG), organism-specific biosystemAdapted from Raza et al. (2008). This pathway is initiated by IFNG binding to its receptor and a subsequent phosphorylation cascade involving a number of the JAK and STAT family of proteins. Several ...
  • Viral carcinogenesis, organism-specific biosystem (from KEGG)
    Viral carcinogenesis, organism-specific biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
  • Viral carcinogenesis, conserved biosystem (from KEGG)
    Viral carcinogenesis, conserved biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • MGC126524

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
double-stranded RNA binding IDA
Inferred from Direct Assay
more info
 
eukaryotic translation initiation factor 2alpha kinase activity TAS
Traceable Author Statement
more info
PubMed 
non-membrane spanning protein tyrosine kinase activity IEA
Inferred from Electronic Annotation
more info
 
poly(A) RNA binding IDA
Inferred from Direct Assay
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein kinase activity IMP
Inferred from Mutant Phenotype
more info
 
protein phosphatase type 2A 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 
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
 
modulation by virus of host morphology or physiology TAS
Traceable Author Statement
more info
 
modulation by virus of host process TAS
Traceable Author Statement
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
 
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
 
response to interferon-alpha IDA
Inferred from Direct Assay
more info
PubMed 
response to virus IMP
Inferred from Mutant Phenotype
more info
PubMed 
transcription, DNA-templated IEA
Inferred from Electronic Annotation
more info
 
translation IEA
Inferred from Electronic Annotation
more info
 
viral life cycle TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
membrane IDA
Inferred from Direct Assay
more info
PubMed 
nucleus IEA
Inferred from Electronic Annotation
more info
 
perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
Preferred Names
interferon-induced, double-stranded RNA-activated protein kinase
Names
interferon-induced, double-stranded RNA-activated protein kinase
p68 kinase
eIF-2A protein kinase 2
P1/eIF-2A protein kinase
tyrosine-protein kinase EIF2AK2
interferon-inducible elF2alpha kinase
double stranded RNA activated protein kinase
protein phosphatase 1, regulatory subunit 83
protein kinase, interferon-inducible double stranded RNA dependent
NP_001129123.1
NP_001129124.1
NP_002750.1

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 

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

mRNA and Protein(s)

  1. NM_001135651.2NP_001129123.1  interferon-induced, double-stranded RNA-activated protein kinase isoform a

    See proteins identical to 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
    Conserved Domains (3) summary
    smart00220
    Location:267534
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd00048
    Location:100165
    DSRM; Double-stranded RNA binding motif. Binding is not sequence specific but is highly specific for double stranded RNA. Found in a variety of proteins including dsRNA dependent protein kinase PKR, RNA helicases, Drosophila staufen protein, E. coli RNase III, ...
    cl09925
    Location:266534
    PKc_like; Protein Kinases, catalytic domain
  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
    Conserved Domains (3) summary
    smart00220
    Location:252493
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd00048
    Location:100165
    DSRM; Double-stranded RNA binding motif. Binding is not sequence specific but is highly specific for double stranded RNA. Found in a variety of proteins including dsRNA dependent protein kinase PKR, RNA helicases, Drosophila staufen protein, E. coli RNase III, ...
    cl09925
    Location:248493
    PKc_like; Protein Kinases, catalytic domain
  3. NM_002759.3NP_002750.1  interferon-induced, double-stranded RNA-activated protein kinase isoform a

    See proteins identical to 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, ENST00000395127
    Conserved Domains (3) summary
    smart00220
    Location:267534
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd00048
    Location:100165
    DSRM; Double-stranded RNA binding motif. Binding is not sequence specific but is highly specific for double stranded RNA. Found in a variety of proteins including dsRNA dependent protein kinase PKR, RNA helicases, Drosophila staufen protein, E. coli RNase III, ...
    cl09925
    Location:266534
    PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000002.12 

    Range
    37105138..37157047
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

  1. AC_000134.1 

    Range
    37072482..37124338
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018913.2 

    Range
    37261631..37313513
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)