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

    Gene ID: 440275, updated on 10-Dec-2024

    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
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    Genomic context

    See EIF2AK4 in Genome Data Viewer
    Location:
    15q15.1
    Exon count:
    39
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (39934115..40035591)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (37739435..37840931)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (40226316..40327792)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene G protein-coupled receptor 176 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40176182-40176852 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40176853-40177522 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40177802-40178334 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40178335-40178866 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:40179399-40179929 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40186807-40187332 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40200676-40201176 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:40209802-40209908 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40211506-40212311 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6313 Neighboring gene GPR176 divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9218 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6314 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9219 Neighboring gene small nucleolar RNA U13 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40251723-40252224 Neighboring gene H3 histone pseudogene 38 Neighboring gene Sharpr-MPRA regulatory region 10520 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40314575-40315076 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40315077-40315576 Neighboring gene uncharacterized LOC124903471 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:40330400-40331345 Neighboring gene H3K27ac hESC enhancer GRCh37_chr15:40331346-40332290 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9222 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9223 Neighboring gene SRP14 divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9224 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:40347031-40347610 Neighboring gene signal recognition particle 14 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9226 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:40354716-40355551 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9227 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9228

    Genomic regions, transcripts, and products

    Expression

    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    BioGRID CRISPR Screen Phenotypes (76 hits/1277 screens)

    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

    Pathways from PubChem

    Interactions

    General gene information

    Clone Names

    • KIAA1338

    Gene Ontology Provided by GOA

    Items 1 - 25 of 27
    Function Evidence Code Pubs
    enables 3-phosphoinositide-dependent protein kinase activity  
    enables AMP-activated protein kinase activity  
    enables ATP binding  
    enables DNA-dependent protein kinase activity  
    enables Rho-dependent protein serine/threonine kinase activity  
    enables eukaryotic translation initiation factor 2alpha kinase activity  
    enables eukaryotic translation initiation factor 2alpha kinase activity PubMed 
    enables eukaryotic translation initiation factor 2alpha kinase activity PubMed 
    enables eukaryotic translation initiation factor 2alpha kinase activity PubMed 
    enables histone H2AS1 kinase activity  
    enables histone H2AS121 kinase activity  
    enables histone H2AT120 kinase activity  
    enables histone H2AXS139 kinase activity  
    enables histone H2BS14 kinase activity  
    enables histone H2BS36 kinase activity  
    enables histone H3S10 kinase activity  
    enables histone H3S28 kinase activity  
    enables histone H3S57 kinase activity  
    enables histone H3T11 kinase activity  
    enables histone H3T3 kinase activity  
    enables histone H3T45 kinase activity  
    enables histone H3T6 kinase activity  
    enables histone H4S1 kinase activity  
    enables protein serine kinase activity  
    enables protein serine/threonine kinase activity  
    enables ribosomal protein S6 kinase activity  
    enables tRNA binding  
    Items 1 - 25 of 27
    Items 1 - 25 of 33
    Process Evidence Code Pubs
    involved_in DNA damage checkpoint signaling  
    involved_in GCN2-mediated signaling PubMed 
    involved_in GCN2-mediated signaling PubMed 
    involved_in GCN2-mediated signaling  
    involved_in T cell activation involved in immune response  
    involved_in adaptive immune response  
    involved_in cellular response to UV  
    involved_in cellular response to amino acid starvation  
    involved_in cellular response to amino acid starvation PubMed 
    involved_in cellular response to cold PubMed 
    involved_in chromatin remodeling  
    involved_in defense response to virus  
    involved_in eiF2alpha phosphorylation in response to endoplasmic reticulum stress PubMed 
    involved_in learning  
    involved_in long-term memory  
    involved_in negative regulation by host of viral genome replication  
    involved_in negative regulation of CREB transcription factor activity  
    involved_in negative regulation of neuron differentiation  
    involved_in negative regulation of translational initiation  
    involved_in negative regulation of translational initiation in response to stress  
    involved_in negative regulation of translational initiation in response to stress  
    involved_in neuron projection extension  
    involved_in positive regulation of adaptive immune response  
    involved_in positive regulation of defense response to virus by host  
    involved_in positive regulation of long-term synaptic potentiation  
    involved_in positive regulation of translational initiation in response to starvation  
    involved_in protein autophosphorylation  
    involved_in protein phosphorylation  
    involved_in regulation of feeding behavior  
    involved_in regulation of translational initiation  
    involved_in regulation of translational initiation by eIF2 alpha phosphorylation PubMed 
    involved_in regulation of translational initiation by eIF2 alpha phosphorylation  
    involved_in viral translation  
    Items 1 - 25 of 33
    Component Evidence Code Pubs
    is_active_in cytoplasm  
    located_in cytoplasm  
    is_active_in cytosol  
    located_in cytosolic ribosome  
    is_active_in nucleus  

    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)

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    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_001013703.4 → NP_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
      C9JEC4, Q69YL7, Q6DC97, Q96GN6, Q9H5K1, Q9NSQ3, Q9NSZ5, Q9P2K8, Q9UJ56
      UniProtKB/TrEMBL
      H0YME5
      Related
      ENSP00000263791.5, ENST00000263791.10
      Conserved Domains (8) summary
      smart00220
      Location:590 → 1001
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      COG0124
      Location:1065 → 1490
      HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]
      cd14012
      Location:299 → 538
      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:583 → 999
      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:296 → 539
      Pkinase; Protein kinase domain
      pfam05773
      Location:18 → 134
      RWD; RWD domain
      cl00266
      Location:1395 → 1641
      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:1061 → 1385
      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: 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_000015.10 Reference GRCh38.p14 Primary Assembly

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

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      37739435..37840931
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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