Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
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
    DNA
    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
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 4165 36 315 - 2007 17488873
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepharynx   highly
     stomach   highly
    Lymphoid/Immunelymph node   highly
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Connectivebone  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    mono polymer heteromer , trimer
    HOMOLOGY
    interspecies homolog to murine Eif2a
    Homologene
    FAMILY
  • EIF-2-alpha family
  • CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic,ribosome
    intracellular,nucleus
    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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • 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
  • INTERACTION
    DNA
    RNA binding
    small molecule
    protein
  • 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
    REGULATION
    Phosphorylated by EIF2AK3 phosphorylates EIF2S1, which blocks the initiation step of translation, reducing new protein synthesis
    ASSOCIATED DISORDERS
    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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyinfectious 
    promoting EIF2S1 dephosphorylation rescues vital translation rates and is thereby neuroprotective in prion disease
    ANIMAL & CELL MODELS
  • reducing Eif2s1 levels in prion-diseased mice significantly increases survival