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

    Gene ID: 5610, updated on 9-Jun-2024

    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; AllianceGenome:HGNC:9437
    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; DYT33; 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. The encoded protein plays an important role in the innate immune response against multiple DNA and RNA viruses. [provided by RefSeq, Jul 2021]
    Annotation information
    Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
    Expression
    Ubiquitous expression in bone marrow (RPKM 8.7), brain (RPKM 6.4) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See EIF2AK2 in Genome Data Viewer
    Location:
    2p22.2
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (37099210..37156980, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (37106342..37164108, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (37326353..37384123, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene striatin Neighboring gene RNA, U6 small nuclear 577, pseudogene Neighboring gene MPRA-validated peak3656 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr2:37189639-37189834 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11352 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:37230067-37230233 Neighboring gene HEAT repeat containing 5B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15578 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15579 Neighboring gene G-patch domain containing 11 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11353 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11354 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15580 Neighboring gene ARL14EP pseudogene 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:37416294-37416819 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:37416820-37417344 Neighboring gene sulfotransferase family 6B member 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11355 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:37431745-37432548 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:37432549-37433353 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr2:37441863-37443062 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

    Clone Names

    • MGC126524

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in antiviral innate immune response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cellular response to amino acid starvation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in defense response to virus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in eiF2alpha phosphorylation in response to endoplasmic reticulum stress IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in endoplasmic reticulum unfolded protein response IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of cell population proliferation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of osteoblast proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of translation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of translation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of viral genome replication IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of MAPK cascade IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of chemokine production ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of cytokine production ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of non-canonical NF-kappaB signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of stress-activated MAPK cascade ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein autophosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of NLRP3 inflammasome complex assembly ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of hematopoietic progenitor cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of hematopoietic stem cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of hematopoietic stem cell proliferation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in response to interferon-alpha IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to virus IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in translation IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    is_active_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in membrane HDA PubMed 
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in 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 RNA-regulated
    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_047301071.1
    XP_047301072.1
    XP_054198993.1
    XP_054198994.1
    XP_054198995.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_030351.2 RefSeqGene

      Range
      5000..62770
      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
      A8K3P0, D6W584, E9PC80, P19525, Q52M43, Q7Z6F6, Q9UIR4
      UniProtKB/TrEMBL
      B7ZKK7
      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/TrEMBL
      B7ZKK7
      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_002759.4NP_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
      A8K3P0, D6W584, E9PC80, P19525, Q52M43, Q7Z6F6, Q9UIR4
      UniProtKB/TrEMBL
      B7ZKK7
      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: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      37099210..37156980 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047445116.1XP_047301072.1  interferon-induced, double-stranded RNA-activated protein kinase isoform X2

      UniProtKB/TrEMBL
      A0A7P0Z4M0, B7ZKK7
      Related
      ENSP00000506455.1, ENST00000679979.1
    2. XM_011532987.3XP_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
      A8K3P0, D6W584, E9PC80, P19525, Q52M43, Q7Z6F6, Q9UIR4
      UniProtKB/TrEMBL
      B7ZKK7
      Related
      ENSP00000505772.1, ENST00000681507.1
      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
    3. XM_047445115.1XP_047301071.1  interferon-induced, double-stranded RNA-activated protein kinase isoform X2

      UniProtKB/TrEMBL
      A0A7P0Z4M0, B7ZKK7

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      37106342..37164108 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054343020.1XP_054198995.1  interferon-induced, double-stranded RNA-activated protein kinase isoform X2

      UniProtKB/TrEMBL
      A0A7P0Z4M0, B7ZKK7
    2. XM_054343018.1XP_054198993.1  interferon-induced, double-stranded RNA-activated protein kinase isoform X1

      UniProtKB/Swiss-Prot
      A8K3P0, D6W584, E9PC80, P19525, Q52M43, Q7Z6F6, Q9UIR4
      UniProtKB/TrEMBL
      B7ZKK7
    3. XM_054343019.1XP_054198994.1  interferon-induced, double-stranded RNA-activated protein kinase isoform X2

      UniProtKB/TrEMBL
      A0A7P0Z4M0, B7ZKK7