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Eif2ak4 eukaryotic translation initiation factor 2 alpha kinase 4 [ Mus musculus (house mouse) ]

Gene ID: 27103, updated on 3-Apr-2024

Summary

Official Symbol
Eif2ak4provided by MGI
Official Full Name
eukaryotic translation initiation factor 2 alpha kinase 4provided by MGI
Primary source
MGI:MGI:1353427
See related
Ensembl:ENSMUSG00000005102 AllianceGenome:MGI:1353427
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as
GCN2; MGCN2; 2610011M03
Summary
Enables eukaryotic translation initiation factor 2alpha kinase activity and tRNA binding activity. Involved in several processes, including GCN2-mediated signaling; learning or memory; and regulation of translational initiation. Acts upstream of or within cellular response to starvation; endoplasmic reticulum unfolded protein response; and regulation of translation. Part of polysome. Is expressed in several structures, including gut; hemolymphoid system gland; liver; lung; and ovary. Human ortholog(s) of this gene implicated in pulmonary venoocclusive disease. Orthologous to human EIF2AK4 (eukaryotic translation initiation factor 2 alpha kinase 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression
Ubiquitous expression in ovary adult (RPKM 8.2), limb E14.5 (RPKM 7.9) and 28 other tissues See more
Orthologs
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Genomic context

See Eif2ak4 in Genome Data Viewer
Location:
2 E5; 2 59.4 cM
Exon count:
41
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 2 NC_000068.8 (118219065..118305715)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 2 NC_000068.7 (118388583..118475234)

Chromosome 2 - NC_000068.8Genomic Context describing neighboring genes Neighboring gene fibrous sheath-interacting protein 1 Neighboring gene STARR-seq mESC enhancer starr_05456 Neighboring gene STARR-positive B cell enhancer ABC_E7849 Neighboring gene STARR-positive B cell enhancer mm9_chr2:118089004-118089305 Neighboring gene STARR-seq mESC enhancer starr_05457 Neighboring gene RIKEN cDNA 1700054M17 gene Neighboring gene G protein-coupled receptor 176 Neighboring gene STARR-seq mESC enhancer starr_05459 Neighboring gene STARR-positive B cell enhancer ABC_E1594 Neighboring gene STARR-positive B cell enhancer ABC_E9525 Neighboring gene aldo-keto reductase family 1, member B3 pseudogene Neighboring gene signal recognition particle 14

Genomic regions, transcripts, and products

Expression

  • 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

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Variation

Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Targeted (3)  1 citation
  • Chemically induced (ENU) (1) 
  • Endonuclease-mediated (2) 

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Gene Ontology Provided by MGI

Process Evidence Code Pubs
involved_in DNA damage checkpoint signaling IEA
Inferred from Electronic Annotation
more info
 
involved_in GCN2-mediated signaling IDA
Inferred from Direct Assay
more info
PubMed 
involved_in GCN2-mediated signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in GCN2-mediated signaling ISO
Inferred from Sequence Orthology
more info
 
involved_in T cell activation involved in immune response IMP
Inferred from Mutant Phenotype
more info
PubMed 
acts_upstream_of_or_within adaptive immune response IEA
Inferred from Electronic Annotation
more info
 
acts_upstream_of_or_within cell cycle IEA
Inferred from Electronic Annotation
more info
 
acts_upstream_of_or_within cell differentiation IEA
Inferred from Electronic Annotation
more info
 
involved_in cellular response to UV IDA
Inferred from Direct Assay
more info
PubMed 
involved_in cellular response to amino acid starvation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in cellular response to amino acid starvation IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in cellular response to amino acid starvation ISO
Inferred from Sequence Orthology
more info
 
involved_in cellular response to cold ISO
Inferred from Sequence Orthology
more info
 
acts_upstream_of_or_within cellular response to starvation IDA
Inferred from Direct Assay
more info
PubMed 
acts_upstream_of_or_within defense response to virus IEA
Inferred from Electronic Annotation
more info
 
involved_in eiF2alpha phosphorylation in response to endoplasmic reticulum stress ISO
Inferred from Sequence Orthology
more info
 
acts_upstream_of_or_within endoplasmic reticulum unfolded protein response IMP
Inferred from Mutant Phenotype
more info
PubMed 
acts_upstream_of_or_within immune system process IEA
Inferred from Electronic Annotation
more info
 
involved_in learning IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in long-term memory IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation by host of viral genome replication IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of CREB transcription factor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of cytoplasmic translational initiation in response to stress IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in negative regulation of neuron differentiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
acts_upstream_of_or_within negative regulation of translation IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in negative regulation of translational initiation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of translational initiation in response to stress IDA
Inferred from Direct Assay
more info
PubMed 
acts_upstream_of_or_within nervous system development IEA
Inferred from Electronic Annotation
more info
 
involved_in neuron projection extension IMP
Inferred from Mutant Phenotype
more info
PubMed 
acts_upstream_of_or_within phosphorylation IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of adaptive immune response IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of defense response to virus by host IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of gene expression IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of long-term synaptic potentiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of protein phosphorylation ISO
Inferred from Sequence Orthology
more info
 
involved_in positive regulation of translational initiation in response to starvation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of translational initiation in response to starvation IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in protein autophosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in protein phosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
acts_upstream_of_or_within regulation of cell cycle IEA
Inferred from Electronic Annotation
more info
 
involved_in regulation of cytoplasmic translational initiation in response to stress IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of feeding behavior IMP
Inferred from Mutant Phenotype
more info
PubMed 
acts_upstream_of_or_within regulation of translation IEA
Inferred from Electronic Annotation
more info
 
involved_in regulation of translational initiation IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in regulation of translational initiation ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in regulation of translational initiation by eIF2 alpha phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in regulation of translational initiation by eIF2 alpha phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
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 ISO
Inferred from Sequence Orthology
more info
 
acts_upstream_of_or_within regulation of translational initiation in response to stress IDA
Inferred from Direct Assay
more info
PubMed 
involved_in response to endoplasmic reticulum stress IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in viral translation IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in cytosolic ribosome ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
 

General protein information

Preferred Names
eIF-2-alpha kinase GCN2
Names
GCN2 eIF2alpha kinase
GCN2-like protein
NP_001171277.1
NP_001342312.1
NP_001408350.1
NP_001408351.1
NP_038747.2
XP_006499689.1
XP_006499690.1
XP_017174398.1
XP_036018145.1

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.

mRNA and Protein(s)

  1. NM_001177806.2NP_001171277.1  eIF-2-alpha kinase GCN2 isoform 2

    See identical proteins and their annotated locations for NP_001171277.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence and lacks an alternate internal exon in the 5' end compared to variant 1, that causes a frameshift. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AL929163
    Consensus CDS
    CCDS50669.1
    UniProtKB/TrEMBL
    A2AUM2
    Related
    ENSMUSP00000099586.4, ENSMUST00000102527.10
    Conserved Domains (4) summary
    PLN02972
    Location:9581378
    PLN02972; Histidyl-tRNA synthetase
    cd14012
    Location:187425
    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:470886
    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
    cl00266
    Location:12841528
    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 ...
  2. NM_001355383.2NP_001342312.1  eIF-2-alpha kinase GCN2 isoform 3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) lacks three alternate internal exons in the 5' end compared to variant 1, that causes a frameshift. The resulting isoform (3) has a shorter and distinct N-terminus compared to isoform 1.
    Source sequence(s)
    AL929163
    UniProtKB/TrEMBL
    A2AUM2
    Conserved Domains (4) summary
    cd14012
    Location:109347
    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:392808
    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
    cl00266
    Location:12061450
    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 ...
    cl28413
    Location:8801300
    HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]
  3. NM_001421421.1NP_001408350.1  eIF-2-alpha kinase GCN2 isoform 2

    Status: VALIDATED

    Source sequence(s)
    AL929163
  4. NM_001421422.1NP_001408351.1  eIF-2-alpha kinase GCN2 isoform 4

    Status: VALIDATED

    Source sequence(s)
    AL929163
  5. NM_013719.4NP_038747.2  eIF-2-alpha kinase GCN2 isoform 1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AL929163
    Consensus CDS
    CCDS16576.1
    UniProtKB/Swiss-Prot
    A2AUM3, A2AUM4, Q6GQT4, Q6ZPT5, Q8C5S0, Q8CIF5, Q9CT30, Q9CUV9, Q9ESB6, Q9ESB7, Q9ESB8, Q9QZ05
    UniProtKB/TrEMBL
    A2AUM0
    Related
    ENSMUSP00000005233.6, ENSMUST00000005233.12
    Conserved Domains (7) summary
    smart00220
    Location:5891000
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    smart00591
    Location:26137
    RWD; domain in RING finger and WD repeat containing proteins and DEXDc-like helicases subfamily related to the UBCc domain
    COG0124
    Location:10491485
    HisS; Histidyl-tRNA synthetase [Translation, ribosomal structure and biogenesis]
    cd14012
    Location:299537
    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:582998
    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
    cl00266
    Location:13941640
    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:10601384
    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_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000068.8 Reference GRCm39 C57BL/6J

    Range
    118219065..118305715
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_036162252.1XP_036018145.1  eIF-2-alpha kinase GCN2 isoform X2

    UniProtKB/TrEMBL
    A2AUM1, A2AUM2
    Related
    ENSMUSP00000106498.2, ENSMUST00000110874.8
    Conserved Domains (5) summary
    smart00591
    Location:959
    RWD; domain in RING finger and WD repeat containing proteins and DEXDc-like helicases subfamily related to the UBCc domain
    PLN02972
    Location:9921412
    PLN02972; Histidyl-tRNA synthetase
    cd14012
    Location:221459
    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:504920
    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
    cl00266
    Location:13181562
    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 ...
  2. XM_017318909.3XP_017174398.1  eIF-2-alpha kinase GCN2 isoform X1

    UniProtKB/Swiss-Prot
    A2AUM3, A2AUM4, Q6GQT4, Q6ZPT5, Q8C5S0, Q8CIF5, Q9CT30, Q9CUV9, Q9ESB6, Q9ESB7, Q9ESB8, Q9QZ05
    Conserved Domains (5) summary
    smart00591
    Location:26137
    RWD; domain in RING finger and WD repeat containing proteins and DEXDc-like helicases subfamily related to the UBCc domain
    PLN02972
    Location:10431463
    PLN02972; Histidyl-tRNA synthetase
    cd14012
    Location:272510
    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:555971
    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
    cl00266
    Location:13691613
    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 ...
  3. XM_006499626.5XP_006499689.1  eIF-2-alpha kinase GCN2 isoform X4

    UniProtKB/TrEMBL
    A2AUM2
    Conserved Domains (4) summary
    PLN02972
    Location:9471367
    PLN02972; Histidyl-tRNA synthetase
    cd14012
    Location:176414
    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:459875
    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
    cl00266
    Location:12731517
    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 ...
  4. XM_006499627.5XP_006499690.1  eIF-2-alpha kinase GCN2 isoform X5

    UniProtKB/TrEMBL
    A2AUM2
    Related
    ENSMUSP00000106494.2, ENSMUST00000110870.8
    Conserved Domains (4) summary
    PLN02972
    Location:9201340
    PLN02972; Histidyl-tRNA synthetase
    cd14012
    Location:149387
    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:432848
    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
    cl00266
    Location:12461490
    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 ...