ID:PRKRA_HUMAN DESCRIPTION: RecName: Full=Interferon-inducible double stranded RNA-dependent protein kinase activator A; AltName: Full=PKR-associated protein X; AltName: Full=PKR-associating protein X; AltName: Full=Protein activator of the interferon-induced protein kinase; AltName: Full=Protein kinase, interferon-inducible double stranded RNA-dependent activator; FUNCTION: Activates EIF2AK2/PKR in the absence of double stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA production by DICER1 and for subsequent siRNA-mediated post- transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by DICER1. SUBUNIT: Homodimer. Interacts with EIF2AK2/PKR through its DRBM domains. Interacts with DICER1, EIF2C2/AGO2 and TARBP2. Also able to interact with dsRNA. INTERACTION: Q9NZI8:IGF2BP1; NbExp=1; IntAct=EBI-713955, EBI-1053892; Q14558:PRPSAP1; NbExp=1; IntAct=EBI-713955, EBI-724449; Q9Y3U8:RPL36; NbExp=1; IntAct=EBI-713955, EBI-1057689; O60506:SYNCRIP; NbExp=1; IntAct=EBI-713955, EBI-1024357; SUBCELLULAR LOCATION: Cytoplasm, perinuclear region. DOMAIN: Self-association may occur via interactions between DRBM domains as follows: DRBM 1/DRBM 1, DRBM 1/DRBM 2, DRBM 2/DRBM 2 or DRBM 3/DRBM3. PTM: Phosphorylated at Ser-246 in unstressed cells and at Ser-287 in stressed cells. Phosphorylation at Ser-246 appears to be a prerequisite for subsequent phosphorylation at Ser-287. Phosphorylation at Ser-246 and Ser-287 are necessary for activation of EIF2AK2/PKR under conditions of stress. DISEASE: Defects in PRKRA are the cause of dystonia type 16 (DYT16) [MIM:612067]. DYT16 is an early-onset dystonia- parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT16 patients have progressive, generalized dystonia with axial muscle involvement, oro-mandibular (sardonic smile) and laryngeal dystonia and, in some cases, parkinsonian features. SIMILARITY: Belongs to the PRKRA family. SIMILARITY: Contains 3 DRBM (double-stranded RNA-binding) domains.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O75569
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006468 protein phosphorylation GO:0006955 immune response GO:0008285 negative regulation of cell proliferation GO:0009615 response to virus GO:0010586 miRNA metabolic process GO:0030422 production of siRNA involved in RNA interference GO:0031047 gene silencing by RNA GO:0031054 pre-miRNA processing GO:0034599 cellular response to oxidative stress GO:0035196 production of miRNAs involved in gene silencing by miRNA GO:0042473 outer ear morphogenesis GO:0042474 middle ear morphogenesis GO:0043085 positive regulation of catalytic activity GO:0043583 ear development GO:0048705 skeletal system morphogenesis GO:0050821 protein stabilization GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
