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

    Gene ID: 9451, updated on 7-Dec-2024

    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; AllianceGenome:HGNC:3255
    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
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See EIF2AK3 in Genome Data Viewer
    Location:
    2p11.2
    Exon count:
    21
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (88556741..88628145, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (88568747..88640715, complement)
    RS_2024_09 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 MED14-independent group 3 enhancer GRCh37_chr2:88803591-88804790 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:88811519-88812020 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:88817004-88817504 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:88817505-88818005 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr2:88837459-88838658 Neighboring gene uncharacterized LOC101928371 Neighboring gene sperm microtubule inner protein 9 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr2:88899203-88900402 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16168 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16169 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:88926077-88926756 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:88926757-88927436 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:88927437-88928116 Neighboring gene EIF2AK3 divergent transcript Neighboring gene uncharacterized LOC102724805 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:88958311-88959220 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16172 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11733 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16173 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16174 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:88998185-88998359 Neighboring gene uncharacterized LOC105374853 Neighboring gene ribose 5-phosphate isomerase A

    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
    Wolcott-Rallison dysplasia
    MedGen: C0432217 OMIM: 226980 GeneReviews: Not available
    not available

    EBI GWAS Catalog

    Description
    Hundreds of variants clustered in genomic loci and biological pathways affect human height.
    EBI GWAS Catalog
    Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
    EBI GWAS Catalog

    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

    Clone Names

    • DKFZp781H1925

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 3-phosphoinositide-dependent protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables AMP-activated protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables DNA-dependent protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables Hsp90 protein binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables Rho-dependent protein serine/threonine kinase activity 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
     
    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 histone H2AS1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H2AS121 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H2AT120 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H2AXS139 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H2AXY142 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H2BS14 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H2BS36 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3S10 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3S28 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3S57 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3T11 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3T3 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3T45 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3T6 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3Y41 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H4S1 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables misfolded protein binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase activity TAS
    Traceable Author Statement
    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 tyrosine kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables ribosomal protein S6 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 IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in PERK-mediated unfolded protein response TAS
    Traceable Author Statement
    more info
    PubMed 
    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 chromatin remodeling IEA
    Inferred from Electronic Annotation
    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 IBA
    Inferred from Biological aspect of Ancestor
    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 TAS
    Traceable Author Statement
    more info
    PubMed 
    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 cysteine-type endopeptidase activity 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 IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    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
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    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 membrane HDA PubMed 
    is_active_in mitochondria-associated endoplasmic reticulum membrane contact site IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    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
    PKR-like ER kinase
    PRKR-like endoplasmic reticulum kinase
    pancreatic EIF2-alpha kinase
    pancreatic eIF-2alpha kinase
    protein tyrosine kinase EIF2AK3
    NP_001300844.1
    NP_004827.4
    XP_047302384.1
    XP_047302385.1
    XP_047302386.1
    XP_054200611.1
    XP_054200612.1
    XP_054200613.1

    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
      A0A804HIT4, B3KY45, 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
      A0AVH1, A0AVH2, B2RCU9, O95846, Q53QY0, Q53SB1, Q9NZJ5
      UniProtKB/TrEMBL
      B3KY45, Q68DI6
      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: GCF_000001405.40-RS_2024_08

    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
      88556741..88628145 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047446428.1XP_047302384.1  eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1

      UniProtKB/TrEMBL
      B3KY45, Q68DI6
    2. XM_047446429.1XP_047302385.1  eukaryotic translation initiation factor 2-alpha kinase 3 isoform X2

      UniProtKB/TrEMBL
      B3KY45
      Related
      ENSP00000507355.1, ENST00000684642.1
    3. XM_047446430.1XP_047302386.1  eukaryotic translation initiation factor 2-alpha kinase 3 isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      88568747..88640715 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054344636.1XP_054200611.1  eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1

      UniProtKB/TrEMBL
      B3KY45, Q68DI6
    2. XM_054344637.1XP_054200612.1  eukaryotic translation initiation factor 2-alpha kinase 3 isoform X2

      UniProtKB/TrEMBL
      B3KY45
    3. XM_054344638.1XP_054200613.1  eukaryotic translation initiation factor 2-alpha kinase 3 isoform X3