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    EIF2AK3 eukaryotic translation initiation factor 2 alpha kinase 3 [ Homo sapiens (human) ]

    Gene ID: 9451, updated on 19-Jul-2021

    Summary

    Official Symbol
    EIF2AK3provided by HGNC
    Official Full Name
    eukaryotic translation initiation factor 2 alpha kinase 3provided by HGNC
    Primary source
    HGNC:HGNC:3255
    See related
    Ensembl:ENSG00000172071 MIM:604032
    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
    PEK; WRS; PERK
    Summary
    The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in this gene are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015]
    Expression
    Ubiquitous expression in thyroid (RPKM 13.4), stomach (RPKM 10.9) and 25 other tissues See more
    Orthologs
    NEW
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    Genomic context

    See EIF2AK3 in Genome Data Viewer
    Location:
    2p11.2
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (88556741..88627464, complement)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (88856259..88926982, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene forkhead box I3 Neighboring gene uncharacterized LOC101928371 Neighboring gene testis expressed 37 Neighboring gene EIF2AK3 divergent transcript Neighboring gene uncharacterized LOC102724805

    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?

    Phenotypes

    Associated conditions

    Description Tests
    Hundreds of variants clustered in genomic loci and biological pathways affect human height.
    GeneReviews: Not available
    Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy.
    GeneReviews: Not available
    Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
    GeneReviews: Not available
    Wolcott-Rallison dysplasia
    MedGen: C0432217 OMIM: 226980 GeneReviews: Not available
    Compare labs

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp160, precursor env Knockdown of PERK expression increases intracellular HIV-1 Env expression in human and murine cell lines PubMed
    Tat tat HIV-1 Tat induces endoplasmic reticulum (ER) stress response proteins CASP12 (Caspase 12), DDIT3 (CHOP), ROS1, ERN-1 (p-IRE1), EIF2AK3 (p-PERK), and ATF6 in human brain microvascular endothelial cells (HBMECs) PubMed
    tat Exposure of human umbilical vein endothelial cells to HIV-1 Tat causes broad activation of the unfolded-protein response in ER with phosphorylation of PERK, eIF2alpha, and JNK and induction of Grp78/BiP PubMed
    tat Neurons exposed to HIV-1 Tat induces calcium loss from the endoplasmic reticulum via ryanodine receptor (RyR) and increases the phosphorylated levels of PERK, eIF2a, and XBP1 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

    • DKFZp781H1925

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables Hsp90 protein binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables eukaryotic translation initiation factor 2alpha kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables eukaryotic translation initiation factor 2alpha kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables eukaryotic translation initiation factor 2alpha kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables protein phosphatase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein serine/threonine kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables protein threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in ER overload response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in PERK-mediated unfolded protein response TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in angiogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in bone mineralization ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in calcium-mediated signaling ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to amino acid starvation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cellular response to cold IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cellular response to glucose starvation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in chondrocyte development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in eiF2alpha phosphorylation in response to endoplasmic reticulum stress IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in eiF2alpha phosphorylation in response to endoplasmic reticulum stress TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in endocrine pancreas development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in endoplasmic reticulum organization ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in endoplasmic reticulum unfolded protein response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in endoplasmic reticulum unfolded protein response TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in insulin-like growth factor receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of myelination ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of translation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of translation in response to stress IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of translational initiation in response to stress TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in ossification IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in peptidyl-serine phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of protein localization to nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of transcription by RNA polymerase I IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of vascular endothelial growth factor production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    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 ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of translational initiation by eIF2 alpha phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in response to endoplasmic reticulum stress IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in response to manganese-induced endoplasmic reticulum stress IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in skeletal system development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Component Evidence Code Pubs
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in endoplasmic reticulum IC
    Inferred by Curator
    more info
    PubMed 
    located_in endoplasmic reticulum ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in endoplasmic reticulum TAS
    Traceable Author Statement
    more info
    PubMed 
    located_in endoplasmic reticulum membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in endoplasmic reticulum membrane NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
     
    located_in integral component of endoplasmic reticulum membrane NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in membrane HDA PubMed 
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    eukaryotic translation initiation factor 2-alpha kinase 3
    Names
    PRKR-like endoplasmic reticulum kinase
    pancreatic EIF2-alpha kinase
    truncated eukaryotic translation initiation factor 2 alpha kinase 3
    NP_001300844.1
    NP_004827.4
    XP_016860865.1

    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_016424.1 RefSeqGene

      Range
      5113..75836
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1024

    mRNA and Protein(s)

    1. NM_001313915.2NP_001300844.1  eukaryotic translation initiation factor 2-alpha kinase 3 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate 5' exon, uses an alternate 5' terminal exon, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AC062029, AC104134, CB162654, CR749382
      UniProtKB/TrEMBL
      E7ER02, Q68DI6
      Related
      ENSP00000507214.1, ENST00000682892.1
      Conserved Domains (3) summary
      cd09768
      Location:1269
      Luminal_EIF2AK3; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3
      cd14048
      Location:722924
      STKc_EIF2AK3_PERK; Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase
      cl21453
      Location:436512
      PKc_like; Protein Kinases, catalytic domain
    2. NM_004836.7NP_004827.4  eukaryotic translation initiation factor 2-alpha kinase 3 isoform 1 precursor

      See identical proteins and their annotated locations for NP_004827.4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC062029, AC104134, AK128659, CB162654
      Consensus CDS
      CCDS33241.1
      UniProtKB/Swiss-Prot
      Q9NZJ5
      UniProtKB/TrEMBL
      B3KY45
      Related
      ENSP00000307235.3, ENST00000303236.9
      Conserved Domains (3) summary
      cd09768
      Location:104420
      Luminal_EIF2AK3; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3
      cd14048
      Location:8731075
      STKc_EIF2AK3_PERK; Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase
      cl21453
      Location:587663
      PKc_like; Protein Kinases, catalytic domain

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

    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
      88556741..88627464 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017005376.2XP_016860865.1  eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1

      Related
      ENST00000682952.1
      Conserved Domains (3) summary
      cd14048
      Location:645847
      STKc_EIF2AK3_PERK; Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase
      cl14874
      Location:1192
      Luminal_IRE1_like; The Luminal domain, a dimerization domain, of Inositol-requiring protein 1-like proteins
      cl21453
      Location:358447
      PKc_like; Protein Kinases, catalytic domain
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