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FLASH GENE
Symbol EIF2AK4 contributors: mct - updated : 31-08-2012
HGNC name eukaryotic translation initiation factor 2 alpha kinase 4
HGNC id 19687
Location 15q15.1      Physical location : 40.226.346 - 40.327.797
Synonym name GCN2 eIF2alpha kinase
Synonym symbol(s) GCN2, KIAA1338
EC.number 2.7.11.1
DNA
TYPE functioning gene
STRUCTURE 101.45 kb     39 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Binding site
MAPPING cloned   linked   status
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
39 - 5532 - 1649 - -
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text brain
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
Homologene
FAMILY ser/thr family of protein kinases
CATEGORY regulatory
SUBCELLULAR LOCALIZATION intracellular,cytoplasm,cytosolic,ribosome
basic FUNCTION
  • translation regulation
  • role in regulating lipid metabolism during leucine deprivation in addition to regulating amino acid metabolism
  • both EIF2AK3 and EIF2AK4 mediate the cell adaptation to hypoxic stress
  • importance of EIF2AK4 for the immune system to adapt to amino acid starvation by ASNase
  • EIF2AK3, and EIF2AK4 also have a functional role on regulating translation under non-stressed conditions, apart from their long established roles as stress kinases
  • EIF2AK4 pathway was involved in the regulation of NUPR1 through an AARE in the context of amino acid limitation
  • protein kinase considered to be an important sensor for amino acids availability and a potential regulator of redox homeostasis
  • with its downstream signaling pathway, have an important role in the protection against oxidative injuries induced by an amino acid-imbalanced diet, and it can play a critical role in the prevention of oxidative damage
    • CELLULAR PROCESS protein, translation regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • EIF2AK4-ATF4 pathway is critical for maintaining metabolic homeostasis in tumour cells, making it a novel and attractive target for anti-tumour approaches
  • EIF2AK4/ATF4 pathway is involved in this regulation through the presence of an AARE in NUPR1 promoter
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • loss of EIF2AK4 ablated urea-induced phosphorylation of EIF2S1 and reduced the expression of ATF3
  • EIF2AK4 activation and phosphorylation of EIF2S1 in response to MTOR inhibition are necessary for autophagy
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    abrogation of EIF2AK4 expression significantly inhibited tumour growth
    neurologyneurodegenerativealzheimer
    EIF2AK3, EIF2AK4 are potential therapeutic targets for treatment of individuals with Alzheimer disease
    ANIMAL & CELL MODELS
  • Gcn2-/- mice exhibited an increase in protein carbonylation, a marker of oxidative stress, in response to a long-term (24 weeks) leucine-imbalanced diet (ED&
    • 916;Leu)