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    EIF2AK4 eukaryotic translation initiation factor 2 alpha kinase 4 [ Homo sapiens (human) ]

    Gene ID: 440275, updated on 25-Jan-2022

    Summary

    Official Symbol
    EIF2AK4provided by HGNC
    Official Full Name
    eukaryotic translation initiation factor 2 alpha kinase 4provided by HGNC
    Primary source
    HGNC:HGNC:19687
    See related
    Ensembl:ENSG00000128829 MIM:609280; AllianceGenome:HGNC:19687
    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
    GCN2; PVOD2
    Summary
    This gene encodes a member of a family of kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor-2 (EIF2), resulting in the downregulaton of protein synthesis. The encoded protein responds to amino acid deprivation by binding uncharged transfer RNAs. It may also be activated by glucose deprivation and viral infection. Mutations in this gene have been found in individuals suffering from autosomal recessive pulmonary venoocclusive-disease-2. [provided by RefSeq, Mar 2014]
    Expression
    Ubiquitous expression in prostate (RPKM 9.5), thyroid (RPKM 9.2) and 25 other tissues See more
    Orthologs
    NEW
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    Genomic context

    See EIF2AK4 in Genome Data Viewer
    Location:
    15q15.1
    Exon count:
    39
    Annotation release Status Assembly Chr Location
    109.20211119 current GRCh38.p13 (GCF_000001405.39) 15 NC_000015.10 (39934115..40035591)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (40226316..40327792)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105370786 Neighboring gene G protein-coupled receptor 176 Neighboring gene GPR176 divergent transcript Neighboring gene H3 histone pseudogene 38 Neighboring gene Sharpr-MPRA regulatory region 10520 Neighboring gene SRP14 divergent transcript Neighboring gene signal recognition particle 14

    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
    Familial pulmonary capillary hemangiomatosis
    MedGen: C0340848 OMIM: 234810 GeneReviews: Not available
    Compare labs

    EBI GWAS Catalog

    Description
    Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma.
    EBI GWAS Catalog
    Genetic variants near PDGFRA are associated with corneal curvature in Australians.
    EBI GWAS Catalog
    Genome wide association study: searching for genes underlying body mass index in the Chinese.
    EBI GWAS Catalog
    Genome-wide association study supports the role of the immunological system and of the neurodevelopmental processes in response to haloperidol treatment.
    EBI GWAS Catalog

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    Knockdown of GCN2 by siRNA enhances HIV-1 infectivity in HeLa P4 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    integrase gag-pol HIV-1 IN binds GCN2 through its residues 350-500. IN restores protein synthesis following a stress induced by amino acid starvation, which results in GCN2 activation PubMed
    retropepsin gag-pol HIV-1 PR directly cleaves GCN2 at amino acid residues 560-561, which leads to inactivate GCN2 activity PubMed
    gag-pol Viral RNA produced during HIV-1 infection activates GCN2 leading to inhibition of viral RNA translation, and that HIV-1 PR cleaves GCN2 to overcome its antiviral effect PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • KIAA1338

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    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 IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables eukaryotic translation initiation factor 2alpha kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    enables protein kinase activity IBA
    Inferred from Biological aspect of Ancestor
    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 serine/threonine/tyrosine kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables tRNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Process Evidence Code Pubs
    involved_in DNA damage checkpoint signaling IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in GCN2-mediated signaling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in GCN2-mediated signaling ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in T cell activation involved in immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cell cycle IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to UV 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 amino acid starvation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to cold IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cellular response to leucine starvation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in defense response to virus 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 learning ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in long-term memory ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation by host of viral genome replication ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of CREB transcription factor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of neuron differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of translational initiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of translational initiation in response to stress ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in neuron projection extension ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of adaptive immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of defense response to virus by host ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of long-term synaptic potentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of protein phosphorylation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of translational initiation in response to starvation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in protein autophosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in protein phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of feeding behavior ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of translational initiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of translational initiation by eIF2 alpha phosphorylation 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 viral translation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in cytosolic ribosome ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    part_of polysome ISS
    Inferred from Sequence or Structural Similarity
    more info
     

    General protein information

    Preferred Names
    eIF-2-alpha kinase GCN2
    Names
    GCN2 eIF2alpha kinase
    GCN2-like protein
    general control nonderepressible 2
    NP_001013725.2

    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_034053.1 RefSeqGene

      Range
      4992..106468
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001013703.4NP_001013725.2  eIF-2-alpha kinase GCN2

      See identical proteins and their annotated locations for NP_001013725.2

      Status: REVIEWED

      Source sequence(s)
      AB037759, AC012377, AL157497, BC009350, BC014915, BC078179, CN286138
      Consensus CDS
      CCDS42016.1
      UniProtKB/Swiss-Prot
      Q9P2K8
      Related
      ENSP00000263791.5, ENST00000263791.10
      Conserved Domains (8) summary
      smart00220
      Location:5901001
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      COG0124
      Location:10651490
      HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]
      cd14012
      Location:299538
      PK_eIF2AK_GCN2_rpt1; Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2
      cd14046
      Location:583999
      STKc_EIF2AK4_GCN2_rpt2; Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2
      pfam00069
      Location:296539
      Pkinase; Protein kinase domain
      pfam05773
      Location:18134
      RWD; RWD domain
      cl00266
      Location:13951641
      HGTP_anticodon; HGTP anticodon binding domain, as found at the C-terminus of histidyl, glycyl, threonyl and prolyl tRNA synthetases, which are classified as a group of class II aminoacyl-tRNA synthetases (aaRS). In aaRSs, the anticodon binding domain is responsible for ...
      cl00268
      Location:10611385
      class_II_aaRS-like_core; Class II tRNA amino-acyl synthetase-like catalytic core domain. Class II amino acyl-tRNA synthetases (aaRS) share a common fold and generally attach an amino acid to the 3' OH of ribose of the appropriate tRNA. PheRS is an exception in that it attaches ...

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20211119

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

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000015.10 Reference GRCh38.p13 Primary Assembly

      Range
      39934115..40035591
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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