IFN-inducible ds RNA-dependent protein kinase activator A; PKR-associated protein X; protein activator of the interferon-induced protein kinase; protein kinase, interferon-inducible double stranded RNA-dependent activator (PRKRA, PAC,T RAX, HSD14)
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Function
- pro-apoptotic
- activates EIF2AK2 in absence of dsRNA, leading to phosphorylation of EIF2S1/EFI2-alpha inhibition of translation & induction of apoptosis
- interacts with EIF2AK2, dsRNA
- required for siRNA production by DICER1 & for subsequent siRNA-mediated post-transcriptional gene silencing
- does not seem to be required for processing of pre-miRNA to miRNA by DICER1
- phosphorylated at Ser-246 in unstressed cells
- phosphorylated 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 & Ser-287 are necessary for activation of EIF2AK2/PKR under conditions of stress
- phosphorylated on Ser
- interacts with EIF2AK2/PKR through its DRBM domains
- interacts with DICER1, EIF2C2/AGO2 & TARBP2
- also able to interact with dsRNA
Structure
- homodimer
- 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
- belongs to the PRKRA family
- contains 3 DRBM (double-stranded RNA-binding) domains
Compartment
cytoplasm, perinuclear region
Alternative splicing
named isoforms=3
Pathology
- defects in PRKRA are the cause of dystonia type 16