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

Gene ID: 440275, updated on 22-Nov-2020

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
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

Genomic context

See EIF2AK4 in Genome Data Viewer
Location:
15q15.1
Exon count:
39
Annotation release Status Assembly Chr Location
109.20200815 current GRCh38.p13 (GCF_000001405.39) 15 NC_000015.10 (39934115..40035591)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (40226331..40327797)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105370786 Neighboring gene G protein-coupled receptor 176 Neighboring gene GPR176-DT Neighboring gene H3 histone pseudogene 38 Neighboring gene Sharpr-MPRA regulatory region 10520 Neighboring gene SRP14 antisense RNA1 (head to head) 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
Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma.
GeneReviews: Not available
Genetic variants near PDGFRA are associated with corneal curvature in Australians.
GeneReviews: Not available
Genome wide association study: searching for genes underlying body mass index in the Chinese.
GeneReviews: Not available
Genome-wide association study supports the role of the immunological system and of the neurodevelopmental processes in response to haloperidol treatment.
GeneReviews: Not available
Pulmonary venoocclusive disease 2, autosomal recessive
MedGen: C0340848 OMIM: 234810 GeneReviews: Not available
Compare labs

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
ATP binding IEA
Inferred from Electronic Annotation
more info
 
eukaryotic translation initiation factor 2alpha kinase activity IBA
Inferred from Biological aspect of Ancestor
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 ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
protein kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
 
protein serine/threonine kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
protein threonine kinase activity IEA
Inferred from Electronic Annotation
more info
 
tRNA binding ISS
Inferred from Sequence or Structural Similarity
more info
 
Process Evidence Code Pubs
DNA damage checkpoint IEA
Inferred from Electronic Annotation
more info
 
T cell activation involved in immune response ISS
Inferred from Sequence or Structural Similarity
more info
 
adaptive immune response IEA
Inferred from Electronic Annotation
more info
 
cell cycle arrest IEA
Inferred from Electronic Annotation
more info
 
cellular response to UV ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to amino acid starvation IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to amino acid starvation ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to cold IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to leucine starvation ISS
Inferred from Sequence or Structural Similarity
more info
 
defense response to virus IEA
Inferred from Electronic Annotation
more info
 
eiF2alpha phosphorylation in response to endoplasmic reticulum stress IMP
Inferred from Mutant Phenotype
more info
PubMed 
induction by virus of host autophagy ISS
Inferred from Sequence or Structural Similarity
more info
 
learning ISS
Inferred from Sequence or Structural Similarity
more info
 
long-term memory ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation by host of viral genome replication ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of CREB transcription factor activity ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of neuron differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of translational initiation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of translational initiation in response to stress ISS
Inferred from Sequence or Structural Similarity
more info
 
neuron projection extension ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of adaptive immune response ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of defense response to virus by host ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of long-term synaptic potentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of translational initiation in response to starvation ISS
Inferred from Sequence or Structural Similarity
more info
 
protein autophosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
 
protein phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of feeding behavior ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of translational initiation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of translational initiation by eIF2 alpha phosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of translational initiation by eIF2 alpha phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
 
viral translation ISS
Inferred from Sequence or Structural Similarity
more info
 
Component Evidence Code Pubs
cytosolic ribosome IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosolic ribosome ISS
Inferred from Sequence or Structural Similarity
more info
 
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)

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 109.20200815

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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