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FLASH GENE
Symbol PRKRA contributors: mct - updated : 28-12-2016
HGNC name protein kinase, interferon-inducible double stranded RNA dependent activator
HGNC id 9438
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
mono polymer heteromer , dimer , trimer
HOMOLOGY
interspecies homolog to murine Prkra
homolog to murine Rax
Homologene
FAMILY
  • PRKRA family
  • CATEGORY immunity/defense , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • activating PRKR which is an interferon -induced protein and mediates the antiviral effect of the interferons
  • involved in the negative regulation of TP53 function through ubiquitin-dependent proteolysis and playing a critical role in development
  • facilitating the production of small interfering RNA (siRNA) by DICER1
  • PRKRA is an important component in initiating and sustaining the DDX58-dependent antiviral response
  • 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
  • cytoplasmic RISC proteins PRKRA, TARBP2, and DICER1 are steroid receptor RNA activator (SRA) binding nuclear receptor (NR) coregulators that target steroid-responsive promoters and regulate NR activity and downstream gene expression
  • stress-modulated activator of the interferon-induced double-stranded RNA-activated protein kinase (PKR)
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text negative control of cell proliferation immune response
    PATHWAY
    metabolism
    signaling signal transduction
  • the PRKRA-EIF2AK2 pathway represents a potential link between APP accumulation, EIF2AK2 activation and MAPT phosphorylation
  • a component
  • heterodimerizing with PRKR
  • is associated with a ~500 kDa complex that contains DICER1, AGO2, and TARBP2 and it associates with DICER1 to facilitate the production of small interfering RNA
  • INTERACTION
    DNA
    RNA binding to double stranded RNA
    small molecule
    protein
  • binding and activating the interferon induced protein PRKR
  • ring finger-containing protein that can directly bind to TP53 (interaction playing a critical role in embryonic development and tumorigenesis)
  • AGO2, PRKRA and TARBP2 were required for the efficient functioning of DICER1 in cells, and likely one of the roles of these proteins is to assure better synchronization of cleavages triggered by two RNase III domains of DICER1
  • EIF2AK2 activation by PRKRA leads to phosphorylation of translation initiation factor EIF2A, inhibition of protein synthesis, and apoptosis
  • PRKRA and TARBP2 have distinct effects on DICER1-mediated dsRNA processing
  • PRKRA contributes to EIF2AK2 dephosphorylation during HIV-1 replication
  • interface residues conserved between TARBP2 and PRKRA show that the proteins bind to DICER1 in a similar manner and by mutual exclusion
  • 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
  • DDX3X may participate in antiviral innate immunity, at least in part, by translational control of PRKRA
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DYT16
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in esophageal cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice deficient in Rax show reproductive and developmental defects, including reduced body size, craniofacial defects and anterior pituitary hypoplasia