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FLASH GENE
Symbol EIF5A contributors: mct/npt - updated : 19-01-2020
HGNC name eukaryotic translation initiation factor 5A
HGNC id 3300
Location 17p13.1      Physical location : 7.210.317 - 7.215.780
Synonym name
  • eukaryotic initiation factor 5A, hypusine
  • Rev-binding factor
    • Synonym symbol(s) EIF5A1, EIF-5A, uORF, MGC99547, MGC104255, eIF-5A-1
    DNA
    TYPE functioning gene
    STRUCTURE 5.46 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 1256 - 184 - 2012 23132580
    6 - 1284 - 154 - 2012 23132580
    6 - 1340 - 154 - 2012 23132580
    6 - 1355 - 154 - 2012 23132580
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     stomach   highly
    Reproductivefemale systemuterus  highly
    Respiratorylung   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a Kow domain
  • a unique amino acid residue, hypusine, formed posttranslationally via the transfer and hydroxylation of the butylamino-group from the polyamine spermidine to a lys50
    • conjugated Acetylated , ubiquitinated
    HOMOLOGY
    interspecies homolog to bacterial EF-P
    intraspecies homolog to EIF5A2
    Homologene
    FAMILY
  • eIF-5A family
    • CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    intracellular,nuclear envelope,pore
    text
  • reversible acetylation plays a major role in controlling the subcellular localization of EIF5A
    • basic FUNCTION
  • involved in the regulation of apoptosis and cell proliferation
  • only cellular protein that contains the unique polyamine-derived amino acid, hypusine (Park 2006)
  • EIF5A protein and deoxyhypusine/hypusine modification are essential for eukaryotic cell proliferation (Park 2006)
  • contributes to the production of proinflammatory cytokines (Maier 2010)
  • role for EIF5A, relating it to embryogenesis, development and cell differentiation (Parreiras-E-Silv 2010)
  • required for the rapid onset of stress-induced translational repression (Li 2010)
  • unhypusinated EIF5A plays a central role in the regulation of apoptosis (Sun 2010)
  • important role of EIF5A and its hypusination for stem cell differentiation and proliferation
  • essential for the synthesis of a subset of proteins containing proline stretches in all cells
  • is proposed to stimulate the peptidyl transferase activity of the ribosome and facilitate the reactivity of poor substrates like Proline
  • specific role for EIF5A in the cotranslational translocation of proteins into the ER, but not in the posttranslational pathway
  • important for specific cellular processes and play a role in the relief of ribosome stalling caused by specific amino acid sequences, suggesting that these factors are involved in specialized translation
  • role for the translation factor EIF5A and its hypusine modification in the elongation phase of protein synthesis and more specifically in stimulating the production of proteins containing runs of consecutive proline residues
  • crucial role of EIF5A and its hypusination in the regulation of LHR expression in the ovary
  • potential role for EIF5A and its hypusine modification pathway in the course of eukaryotic evolution
  • plays a role in mRNA translation, cellular proliferation, cellular differentiation, and inflammation
  • EIF5A and the enzymes responsible for its hypusination (DHPS and DOHH) are essential for embryonic development
  • as a key factor in translation, EIF5A is vital for cell proliferation and has also been reported to play a role in cell differentiation, apoptosis, and autophagy
    • CELLULAR PROCESS cell life, proliferation/growth
    cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    text specific nuclear export pathway
    PATHWAY
    metabolism amine
    signaling
    polyamine homeostasis
    a component
  • polyamine–hypusine axis is a new tumour suppressor network regulating apoptosis
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • essential cofactor of the HIV1 Rev RNA transport factor
  • stimulating ribosomal peptidyltransferase
  • AMD1 is an enzyme controlling a rate-liming step for the synthesis of spermidine, which is incorporated into EIF5A in the form of the non-standard amino acid hypusine
  • specific interaction between EIF5A and DOHH (Kang 2007)
  • SAT1 has been reported to exert other effects in cells by its interaction with other cellular proteins, but EIF5A is the first target protein specifically acetylated by SAT1
  • EIF5A is closely related to EEF2 function during translation elongation
  • essential nature of both EIF5A and DHPS in mammalian development
  • is a target of STUB1, an E3 ligase with a U-box domain, and STUB1 regulates the EIF5A protein stability via a protein degradation mechanism
  • hypusine modification in EIF5A is crucial for homeostasis in mammals
  • DHPS-mediated hypusine-modification of EIF5A facilitated the translation of RHOA, resulting in the activation of the RHOA signaling pathway and leading to not only increased cell motility, and also increased tumor growth
  • by inhibiting EIF5A hypusination, FSH reduces the expression of MVK that increases LHCGR mRNA expression by abrogating the inhibitory action of MVK
  • DHPS catalyzes the hypusination of EIF5A using the butylamine moiety of spermidine via NAD-dependent oxidative reaction
  • DHPS or DOHH, are both involved in hypusination of EIF5A
    • cell & other
    REGULATION
    activated by by the post-translational synthesis of hypusine and the hypusine modification is essential for cell proliferation
    Other activity of EIF5A was regulated through modification of hypusine, phosphorylation and acetylation
    EIF5A phosphorylation and dephosphorylation cycles regulate translation according to the growth conditions
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target hypusine modification of EIF5A is a potential therapeutic target for preserving pancreatic islet function under inflammatory conditions (Maier 2010)
    ANIMAL & CELL MODELS