Kinase Subfamily PKR

Kinase Classification: Group Other: Family PEK: PKR

PKR (Protein Kinase R) is a member of the stress-responsive PEK kinase family, which is activated by double-stranded RNA during viral infection. It phosphorylates eIF2a, resulting in decreased protein translation, hence the alternative name of EIF2AK2. Several other mechanisms are thought to be able to activate PKR, and other substrates and mechanisms of action have been studied.

Domain Structure

PKR genes have a pair of RNA-binding DSRM domains, followed by the kinase domain. Some fish have a variant PKR, called PKZ, which has Z-DNA binding domains instead, probably still used to bind viral nucleic acids [1].

Classification and Evolution

PKR is a vertebrate-specific gene. It is the target of several viral escape mechanisms, causing the sequence to be extremely fast-evolving [2]. Putative homologs of PKR, lacking the DSRM domains, have been found in excavates, annotated as PKR-like [3], though too evolutionarily distant to be obvious orthologs.

References

1. Rothenburg S, Deigendesch N, Dittmar K, Koch-Nolte F, Haag F, Lowenhaupt K, and Rich A. A PKR-like eukaryotic initiation factor 2alpha kinase from zebrafish contains Z-DNA binding domains instead of dsRNA binding domains. Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1602-7. DOI:10.1073/pnas.0408714102 |
2. Elde NC, Child SJ, Geballe AP, and Malik HS. Protein kinase R reveals an evolutionary model for defeating viral mimicry. Nature. 2009 Jan 22;457(7228):485-9. DOI:10.1038/nature07529 |
3. Manning G, Reiner DS, Lauwaet T, Dacre M, Smith A, Zhai Y, Svard S, and Gillin FD. The minimal kinome of Giardia lamblia illuminates early kinase evolution and unique parasite biology. Genome Biol. 2011 Jul 25;12(7):R66. DOI:10.1186/gb-2011-12-7-r66 |