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Symbol EIF2S1 contributors: mct - updated : 28-12-2016
HGNC name eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa
HGNC id 3265
Location 14q24.1      Physical location : 67.827.033 - 67.853.232
Synonym name
  • eukaryotic translation initiation factor 2, subunit 1 (alpha, 35kD)
  • EIF- 2alpha
  • Synonym symbol(s) EIF-2alpha, EIF-2A, EIF2, EIF-2, EIF2A
    TYPE functioning gene
    STRUCTURE 26.20 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC122438 14q23.3 similar to RIKEN cDNA 1110013H04 LOC387993 14 hypothetical gene supported by BC033546 GPHN 14q23.1/14q23,3 gephyrin C14orf54 14 chromosome 14 open reading frame 54 LOC260329 14q23 splicing factor 3b, subunit 4, 49kD pseudogene MPP5 14q23.3 membrane protein, palmitoylated 5 (MAGUK p55 subfamily member 5) ATP6V1D 14q23-q24.2 ATPase, H+ transporting, lysosomal 34kDa, V1 subunit D EIF2S1 14q21.3 eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa PLEK2 14q23.1-q23.2 pleckstrin 2 FLJ33387 14q24.1 hypothetical protein FLJ33387 PIGH 2p21-p16 phosphatidylinositol glycan, class H LOC390490 14 similar to Ac2-008 ARG2 14q24.1-q24.3 arginase, type II VTI1B 14q23,3 vesicle transport through interaction with t-SNAREs homolog 1B (yeast) COX7A3P 14 cytochrome c oxidase subunit VIIa polypeptide 3 pseudogene RDH11 14q23-q24.3 retinol dehydrogenase 11 (all-trans and 9-cis) RPL21P9 14q23.3 ribosomal protein L21 pseudogene 9 RDH12 14q23.3 retinol dehydrogenase 12 (all-trans and 9-cis) ZFYVE26 14q23.2-q24.2 zinc finger, FYVE domain containing 26 RAD51L1 14q24.1 RAD51-like 1 (S. cerevisiae) RPL7AP5 14 ribosomal protein L7a pseudogene 5
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 4165 36 315 - 2007 17488873
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepharynx   highly
     stomach   highly
    Lymphoid/Immunelymph node   highly
    Respiratoryrespiratory tractlarynx  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Connectivebone  highly
    cell lineage
    cell lines
    at STAGE
    physiological period pregnancy
    Text placenta
    mono polymer heteromer , trimer
    interspecies homolog to murine Eif2a
  • EIF-2-alpha family
  • CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • functioning in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA
  • playing a critical role in the mechanics and regulation of protein synthesis
  • phosphorylation of EIF2S1 coordinately attenuates mRNA translation, prevents oxidative stress, and optimizes ER protein folding to support insulin production
  • EIF2S1 phosphorylation is a key step in maintaining a balance between the life and death of a glucose-deficient cell
  • EIF2S1 phosphorylation is a significant determinant of survival and adaptation of glucose-deficient cells with possible important implications in biological processes that interfere with glucose metabolism
  • is a key translation regulator that plays an important role in cellular stress responses
  • crosstalk between cellular metabolism (fatty acids), pro-inflammatory signaling (STAT3), innate immunity (EIF2AK2), and translational control (EIF2S1) that regulates autophagy
  • ER stress-induced EIF2S1 phosphorylation underlies sensitivity of striatal neurons to pathogenic huntingtin
  • EIF2AK3-EIF2S1 signaling, which is required to maintain ER homeostasis, is also indispensable for EMT cells to invade and metastasize
  • EIF2AK3/EIF2S1-P/ATF4 signaling acts as a brake in the decline of protein synthesis during chronic ER stress by positively regulating signaling downstream of the MTOR activity
  • a component
  • heterotrimer composed of an alpha, a beta and a gamma chain
    RNA binding
    small molecule
  • OGFOD1 plays important proapoptotic roles in the regulation of translation and EIF2AK1-mediated phosphorylation of EIF2S1 in cells subjected to arsenite-induced stress
  • docking of EIF2S1 on EIF2AK2 induces a conformational change that regulates the degree of Ser51 exposure and thus restricts phosphorylation to the proper kinases
  • loss of EIF2AK4 ablated urea-induced phosphorylation of EIF2S1 and reduced the expression of ATF3
  • novel role of PTEN in regulating stress response through modulating the PPP1R15B/EIF2S1 pathway
  • PTPN1 is a physiologically-relevant modulator of ER stress in brown adipocytes and PTPN1 deficiency modulates EIF2AK3-EIF2S1 phosphorylation and protein synthesis
  • induction of DDIT4 gene expression was shown to require the protein kinase EIF2AK3 and enhanced phosphorylation of its substrate EIF2S1
  • EIF2AK4 activation and phosphorylation of EIF2S1 in response to MTOR inhibition are necessary for autophagy
  • novel function of ERN1 in the regulation of EIF2S1 phosphorylation and the translational control
  • PPP1R15A associates with the broadly acting serine/threonine protein phosphatase 1 (PP1) to dephosphorylate EIF2S1
  • preferentially translated PPP1R15A and constitutively expressed PPP1R15B function to dephosphorylate EIF2S1-phosphorylated and restore protein synthesis
  • novel redox signaling pathway, involving NOX4-PPP1R15A interaction and a targeted oxidative inactivation of the PP1 metal center, that sustains EIF2S1 phosphorylation to protect tissues under stress
  • coordinate regulation of UPR by the PPP1R15A- and PPP1R15B-containing EIF2S1 phosphatases to control cell viability
  • cell & other
    Phosphorylated by EIF2AK3 phosphorylates EIF2S1, which blocks the initiation step of translation, reducing new protein synthesis
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    elevated phosphorylation of EIF2S1 has been observed in the brains of Alzheimer disease patients
    constitutional     --over  
    UPR activation and/or increased EIF2S1 levels are seen in patients with AD, PD and prion disease
    Variant & Polymorphism
    Candidate gene
    Therapy target
    promoting EIF2S1 dephosphorylation rescues vital translation rates and is thereby neuroprotective in prion disease
  • reducing Eif2s1 levels in prion-diseased mice significantly increases survival