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FLASH GENE
Symbol EIF2AK1 contributors: mct/npt - updated : 28-12-2016
HGNC name eukaryotic translation initiation factor 2-alpha kinase 1
HGNC id 24921
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal domain is suggested to regulate catalysis in response to heme binding
  • two HRM (heme regulatory motif) repeats
  • conjugated PhosphoP
    mono polymer homomer , dimer , complex
    HOMOLOGY
    interspecies ortholog to murine Eif2ak1
    ortholog to rattus Eif2ak1
    Homologene
    FAMILY
  • Ser/Thr protein kinase family
  • GCN2 subfamily
  • EIF2AK family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • mediating down-regulation of protein synthesis in response to various stress conditions by the phosphorylation of EIF2S1 at Ser-48 and Ser-51
  • inhibiting protein synthesis at the level of initiation
  • essential for regulating globin translation in iron deficiency and in beta-thalassemia
  • playing a critical role in the regulation of protein synthesis by heme iron
  • negative regulation of hemoglobin biosynthesis
  • activated under various cytoplasmic stresses in reticulocytes leading to inhibition of initiation of protein synthesis
  • normally modulates the basal hepatic ER stress tone (
  • functions in response to heme shortage in reticulocytes and aids in the maintenance of a heme:globin ratio of 1:1
  • EIF2AK1-mediated process plays a central role in the cellular infection cycle of the Gram-positive pathogen Listeria
  • CELLULAR PROCESS protein, translation regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • homodimer non-covalently bound in the absence of hemin
  • multiprotein complex containing Hsp90, CDC37 and PPP5C for maturation and activation by autophosporylation
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide, other,
  • two molecules of heme per polypeptide chain
  • ATP
  • two transcription factors, ELK1 and MZF1 implicated in regulating EIF2AK1 expression
  • OGFOD1 plays important proapoptotic roles in the regulation of translation and EIF2AK1-mediated phosphorylation of EIF2S1 in cells subjected to arsenite-induced stress
  • vimentin is a component of a complex that binds to the 5prime-UTR of EIF2AK1 mRNA and regulates its translation
  • protein
    cell & other
    REGULATION
    activated by binding of nitric oxide (NO) to the heme iron in the N-terminal heme-binding domain
    autophosphorylation
    induced by cytochrome P450 inducers such as phenobarbital
    inhibited by hemin by promoting the formation of a disulfide-linked
    homodimer
    binding of carbon monoxide (CO)
    ASSOCIATED DISORDERS
    corresponding disease(s) LEMSPAD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    at the level of translation during stress
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS