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    Eif2ak3 eukaryotic translation initiation factor 2 alpha kinase 3 [ Mus musculus (house mouse) ]

    Gene ID: 13666, updated on 8-Jun-2017
    Official Symbol
    Eif2ak3provided by MGI
    Official Full Name
    eukaryotic translation initiation factor 2 alpha kinase 3provided by MGI
    Primary source
    MGI:MGI:1341830
    See related
    Ensembl:ENSMUSG00000031668 Vega:OTTMUSG00000031093
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Pek; 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 a similar gene in human are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015]
    Orthologs
    Location:
    6; 6 C1
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    106 current GRCm38.p4 (GCF_000001635.24) 6 NC_000072.6 (70844483..70905241)
    Build 37.2 previous assembly MGSCv37 (GCF_000001635.18) 6 NC_000072.5 (70794521..70855234)

    Chromosome 6 - NC_000072.6Genomic Context describing neighboring genes Neighboring gene ribose 5-phosphate isomerase A Neighboring gene predicted gene, 30331 Neighboring gene testis expressed 37 Neighboring gene forkhead box I3

    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    • Alzheimer's disease, organism-specific biosystem (from KEGG)
      Alzheimer's disease, organism-specific biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
    • Alzheimer's disease, conserved biosystem (from KEGG)
      Alzheimer's disease, conserved biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
    • Alzheimers Disease, organism-specific biosystem (from WikiPathways)
      Alzheimers Disease, organism-specific biosystemThis pathway displays current genes, proteolytic events and other processes associated with the progression of Alzheimer's disease. This pathway was adapted from KEGG on 10/7/2011. Note: mitochondria...
    • Apoptosis, organism-specific biosystem (from KEGG)
      Apoptosis, organism-specific biosystemApoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled...
    • Apoptosis, conserved biosystem (from KEGG)
      Apoptosis, conserved biosystemApoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled...
    • Autophagy - animal, organism-specific biosystem (from KEGG)
      Autophagy - animal, organism-specific biosystemAutophagy (or macroautophagy) is a cellular catabolic pathway involving in protein degradation, organelle turnover, and non-selective breakdown of cytoplasmic components, which is evolutionarily cons...
    • Autophagy - animal, conserved biosystem (from KEGG)
      Autophagy - animal, conserved biosystemAutophagy (or macroautophagy) is a cellular catabolic pathway involving in protein degradation, organelle turnover, and non-selective breakdown of cytoplasmic components, which is evolutionarily cons...
    • 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...
    • 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 ...
    • 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...
    • Metabolism of proteins, organism-specific biosystem (from REACTOME)
      Metabolism of proteins, organism-specific biosystemcomputationally inferred pathway (not manually curated)
    • Mitophagy - animal, organism-specific biosystem (from KEGG)
      Mitophagy - animal, organism-specific biosystemMitochondria act as the energy powerhouse of the cell, and are essential for eukaryotic cells to grow and function normally. However, deleterious byproducts of oxidative phosphorylation process calle...
    • Mitophagy - animal, conserved biosystem (from KEGG)
      Mitophagy - animal, conserved biosystemMitochondria act as the energy powerhouse of the cell, and are essential for eukaryotic cells to grow and function normally. However, deleterious byproducts of oxidative phosphorylation process calle...
    • Non-alcoholic fatty liver disease (NAFLD), organism-specific biosystem (from KEGG)
      Non-alcoholic fatty liver disease (NAFLD), organism-specific biosystemNon-alcoholic fatty liver disease (NAFLD) represents a spectrum ranging from simple steatosis to more severe steatohepatitis with hepatic inflammation and fibrosis, known as nonalcoholic steatohepati...
    • Non-alcoholic fatty liver disease (NAFLD), conserved biosystem (from KEGG)
      Non-alcoholic fatty liver disease (NAFLD), conserved biosystemNon-alcoholic fatty liver disease (NAFLD) represents a spectrum ranging from simple steatosis to more severe steatohepatitis with hepatic inflammation and fibrosis, known as nonalcoholic steatohepati...
    • PERK regulates gene expression, organism-specific biosystem (from REACTOME)
      PERK regulates gene expression, organism-specific biosystemcomputationally inferred pathway (not manually curated)
    • 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...
    • Translation Factors, organism-specific biosystem (from WikiPathways)
      Translation Factors, organism-specific biosystem
      Translation Factors
    • Unfolded Protein Response (UPR), organism-specific biosystem (from REACTOME)
      Unfolded Protein Response (UPR), organism-specific biosystemcomputationally inferred pathway (not manually curated)

    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    Hsp90 protein binding ISO
    Inferred from Sequence Orthology
    more info
     
    enzyme binding ISO
    Inferred from Sequence Orthology
    more info
     
    eukaryotic initiation factor eIF2 binding IC
    Inferred by Curator
    more info
    PubMed 
    eukaryotic translation initiation factor 2alpha kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    eukaryotic translation initiation factor 2alpha kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    eukaryotic translation initiation factor 2alpha kinase activity ISO
    Inferred from Sequence Orthology
    more info
     
    identical protein binding ISO
    Inferred from Sequence Orthology
    more info
     
    kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    nucleotide binding IEA
    Inferred from Electronic Annotation
    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
    PubMed 
    protein phosphatase binding ISO
    Inferred from Sequence Orthology
    more info
     
    protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein serine/threonine kinase activity ISO
    Inferred from Sequence Orthology
    more info
     
    transferase activity IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    ER overload response ISO
    Inferred from Sequence Orthology
    more info
     
    PERK-mediated unfolded protein response IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    SREBP signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    activation of cysteine-type endopeptidase activity involved in apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    angiogenesis ISO
    Inferred from Sequence Orthology
    more info
     
    bone mineralization IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    calcium-mediated signaling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cellular response to amino acid starvation ISO
    Inferred from Sequence Orthology
    more info
     
    cellular response to cold ISO
    Inferred from Sequence Orthology
    more info
     
    cellular response to glucose starvation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cellular response to glucose starvation ISO
    Inferred from Sequence Orthology
    more info
     
    chondrocyte development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    eiF2alpha phosphorylation in response to endoplasmic reticulum stress ISO
    Inferred from Sequence Orthology
    more info
     
    endocrine pancreas development ISO
    Inferred from Sequence Orthology
    more info
     
    endoplasmic reticulum organization IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    endoplasmic reticulum unfolded protein response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    endoplasmic reticulum unfolded protein response IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    endoplasmic reticulum unfolded protein response ISO
    Inferred from Sequence Orthology
    more info
     
    fat cell differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    insulin-like growth factor receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    lactation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of myelination IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of translation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of translation IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    negative regulation of translation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of translation in response to endoplasmic reticulum stress IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of translation in response to stress ISO
    Inferred from Sequence Orthology
    more info
     
    ossification ISO
    Inferred from Sequence Orthology
    more info
     
    pancreas development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    phosphorylation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    positive regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of gene expression ISO
    Inferred from Sequence Orthology
    more info
     
    positive regulation of glutathione biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of protein binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of protein localization to nucleus IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of transcription from RNA polymerase I promoter IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of transcription from RNA polymerase I promoter ISO
    Inferred from Sequence Orthology
    more info
     
    positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of vascular endothelial growth factor production IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of vascular endothelial growth factor production ISO
    Inferred from Sequence Orthology
    more info
     
    protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein autophosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    protein autophosphorylation ISO
    Inferred from Sequence Orthology
    more info
     
    protein homooligomerization ISO
    Inferred from Sequence Orthology
    more info
     
    protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    protein phosphorylation ISO
    Inferred from Sequence Orthology
    more info
     
    regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway ISO
    Inferred from Sequence Orthology
    more info
     
    regulation of fatty acid metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of translation IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of translational initiation by eIF2 alpha phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of translational initiation by eIF2 alpha phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    response to endoplasmic reticulum stress IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to endoplasmic reticulum stress IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    response to endoplasmic reticulum stress ISO
    Inferred from Sequence Orthology
    more info
     
    response to unfolded protein IEA
    Inferred from Electronic Annotation
    more info
     
    skeletal system development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    translation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    PubMed 
    endoplasmic reticulum membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    integral component of membrane IEA
    Inferred from Electronic Annotation
    more info
     
    membrane ISO
    Inferred from Sequence Orthology
    more info
     
    perinuclear region of cytoplasm ISO
    Inferred from Sequence Orthology
    more info
     
    Preferred Names
    eukaryotic translation initiation factor 2-alpha kinase 3
    Names
    PRKR-like endoplasmic reticulum kinase
    pancreatic eIF2-alpha kinase
    NP_001300847.1
    NP_034251.2
    XP_006505564.1
    XP_011239504.1

    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.

    mRNA and Protein(s)

    1. NM_001313918.1NP_001300847.1  eukaryotic translation initiation factor 2-alpha kinase 3 isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks multiple alternate 3' exons and uses an alternate 3' terminal exon, compared to variant 1. The encoded isoform (2) has a distinct and shorter C-terminus, compared to isoform 1.
      Source sequence(s)
      AC156398, AK010397
      Consensus CDS
      CCDS85063.1
      UniProtKB/Swiss-Prot
      Q9Z2B5
      UniProtKB/TrEMBL
      A0A0R4J1Y1
      Related
      ENSMUSP00000123759.1, OTTMUSP00000040628, ENSMUST00000162950.1, OTTMUST00000077033
      Conserved Domains (1) summary
      cl14874
      Location:100127
      Luminal_IRE1_like; The Luminal domain, a dimerization domain, of Inositol-requiring protein 1-like proteins
    2. NM_010121.3NP_034251.2  eukaryotic translation initiation factor 2-alpha kinase 3 isoform 1 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC155842, BC054809, BP762515
      Consensus CDS
      CCDS20223.1
      UniProtKB/TrEMBL
      E9QQ30, Q7TQC8
      Related
      ENSMUSP00000034093.8, OTTMUSP00000040627, ENSMUST00000034093.14, OTTMUST00000077032
      Conserved Domains (4) summary
      cd09768
      Location:100416
      Luminal_EIF2AK3; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3
      smart00220
      Location:8791071
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd14048
      Location:8741073
      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:583671
      PKc_like; Protein Kinases, catalytic domain

    RefSeqs of Annotated Genomes: Mus musculus Annotation Release 106 details...Open this link in a new tab

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

    Reference GRCm38.p4 C57BL/6J

    Genomic

    1. NC_000072.6 Reference GRCm38.p4 C57BL/6J

      Range
      70844483..70905241
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011241202.2XP_011239504.1  eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1

      Conserved Domains (4) summary
      cd09768
      Location:100416
      Luminal_EIF2AK3; The Luminal domain, a dimerization domain, of the Serine/Threonine protein kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3
      smart00220
      Location:8781070
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd14048
      Location:8731072
      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:582670
      PKc_like; Protein Kinases, catalytic domain
    2. XM_006505501.1XP_006505564.1  eukaryotic translation initiation factor 2-alpha kinase 3 isoform X2

      Conserved Domains (4) summary
      smart00220
      Location:642834
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd14048
      Location:637836
      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:28179
      Luminal_IRE1_like; The Luminal domain, a dimerization domain, of Inositol-requiring protein 1-like proteins
      cl21453
      Location:346434
      PKc_like; Protein Kinases, catalytic domain
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