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FLASH GENE
Symbol EIF2AK2 contributors: mct/npt/pgu - updated : 23-12-2015
HGNC name eukaryotic translation initiation factor 2-alpha kinase 2
HGNC id 9437
Location 2p22.2      Physical location : 37.333.698 - 37.384.190
Synonym name
  • protein kinase, interferon-inducible double stranded RNA
  • dependent
  • P1/eIF-2A protein kinase
  • eIF-2A protein kinase 2
  • p68 kinase
  • protein kinase RNA-activated
  • Synonym symbol(s) DSRNA-PK, PRK, EIF2AK1, PRKR, PKR, MGC126524, PPP1R83
    EC.number 2.7.11.1/2.7.10.2
    DNA
    TYPE functioning gene
    STRUCTURE 50.49 kb     17 Exon(s)
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    text variants 1 and 2 both encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 2930 62 551 - 1998 9687506
    variant 2-isoform a
    17 - 2696 62 551 - 1998 9687506
    variant 2-isoform a
    14 - 2266 57.3 510 - 1998 9687506
    variant 3-isoform b
    - - 1945 - 200 - 1998 9687506
    EXPRESSION
    Type widely
    constitutive of
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/liningepidermis  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal RNA binding motif R1 and R2, dsRNA-binding domain (dsRBD)
  • two DRBM (double-stranded RNA-binding) domains
  • a C-terminal kinase domain
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • ser/thr protein kinase family
  • GCN2 subfamily
  • CATEGORY enzyme , immunity/defense , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • functioning as a receptor for dsRNA signaling and triggering apoptosis through FADD-mediated death signaling
  • inhibiting protein synthesis through phosphorylation of eukaryotic protein synthesis initiation factor 2 alpha subunit
  • involved in the ER stress-mediated signaling pathway
  • essential component of the muscle development machinery and forms a functional complex with MAPK14 and/or Akt
  • functional direct player that coordinates skeletal muscle differentiation via MAPK14/AKT pathways
  • key component of innate immunity, a process in which it senses pathogenic RNA
  • critical role in apoptosis induced by a variety of stresses
  • can modulate transcription, as revealed by its ability to prevent the capacity of DHX9 to catalyze transactivating response (TAR)-mediated type 1 human immunodeficiency virus (HIV-1) gene regulation
  • activated during viral infection and phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF2), leading to inhibition of translation and viral replication
  • EIF2AK2 and HCK were critical for DON-induced ribosomal recruitment of MAPK14, its subsequent phosphorylation, and, ultimately, MAPK14-driven proinflammatory cytokine expression
  • regulates the upstream central transmitters of insulin signaling, IRS1 and IRS2, through different mechanisms
  • EIF2AK2 finely tunes the network activity that must be maintained while storing a given episode during learning
  • critical role in inflammasome activation, indicating that it should be possible to pharmacologically target this molecule to treat inflammation
  • crosstalk between cellular metabolism (fatty acids), pro-inflammatory signaling (STAT3), innate immunity (EIF2AK2), and translational control (EIF2S1) that regulates autophagy
  • is a link between CD40-TRAF signaling and stimulation of the autophagy pathway
  • ability of EIF2AK2 to balance neuroinflammation by selectively modulating key cytokines and chemokines in CNS resident and CD4 T cells
  • mediates angiogenesis through a VEGFA pathway
  • regulates inflammasome-dependent cytokine release
  • activator of the inflammasome and double-stranded RNA-dependent protein kinase R
  • potential role for snoRNAs in EIF2AK2 activation during metabolic stress
  • CELLULAR PROCESS cell life, cell death/apoptosis
    protein, translation/synthesis
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling signal transduction
  • second messenger in a number of pathways
  • the PRKRA-EIF2AK2 pathway represents a potential link between APP accumulation, EIF2AK2 activation and MAPT phosphorylation
  • a component
  • heterodimerizing with PRKRA
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • regulates IRS2, in the liver, at the transcriptional rather than the posttranslational level, and this effect is mediated by the transcription factor, FOXO1
  • PRKRA is a stress-modulated activator of interferon (IFN)-induced double-stranded (ds) RNA-activated protein kinase (EIF2AK2) and is an important regulator of EIF2AK2-dependent signaling pathways
  • EIF2AK2 activation by PRKRA leads to phosphorylation of translation initiation factor EIF2A, inhibition of protein synthesis, and apoptosis
  • EIF2AK2 positively regulates the differentiation of osteoblasts by mediating GSK3B activity through a CTNNB1-independent pathway
  • physically interacts with multiple inflammasome components, including NLR family pyrin domain-containing 3 (NLRP3)
  • HMGB1 hyperacetylation and release, and inflammasome activation, are regulated by EIF2AK2
  • regulates the activation of the NLRP3, NLRP1, AIM2, and NLRC4 inflammasomes, but its activity does not determine which inflammasome will be activated in response to a specific stimulus
  • unsuspected mechanism of autophagy control that involves STAT3 and EIF2AK2 as interacting partners
  • STAT3 may act as a competitive inhibitor of EIF2AK2
  • activation of double-stranded RNA-activated protein kinase (EIF2AK2) by interferon-stimulated gene 15 (ISG15) modification down-regulates protein translation
  • PRKRA contributes to EIF2AK2 dephosphorylation during HIV-1 replication
  • influence the isoform and the level of expression of the proto-oncogene MYC
  • stress-induced phosphorylation of PRKRA is essential for PRKRA association with EIF2AK2 leading to EIF2AK2 activation
  • unexpected function for PRKRA as a negative regulator of EIF2AK2 in the context of postnatal anterior pituitary tissue, and critical role for the regulation of EIF2AK2 activity for normal development
  • cell & other
  • MAPKH activating NFKB, STAT1, ATF2 in inflammatory response
  • regulating dsRNA induction of TNF alpha in epithelial cells
  • REGULATION
    activated by by CD40 via TRAF6 and TRAF2
    induced by interferon
    oxidative stress (induces EIF2AK2 expression essentially via the IFN-gamma activation signal)
    Other positively regulated by the embryonic stem cell transcription factor POU5F1
    regulated by NCK1 (NCK1 as a novel endogenous regulator of EIF2AK2 and support the notion that NCK1-EIF2AK2 interaction could be a way to limit EIF2AK2 activatio)
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS