Intersection of selenoproteins and kinase signalling

• Majority of human selenoproteins are of thioredoxin-like structure
• Thx structure predicted for selenoprotein N explains disease mutation effects
• A protein kinase-like domain has been recently predicted in Selenoprotein O
• A separate selenocysteine region in Selenoprotein O may serve oxidoreductase function
• Selenoprotein O, probably example of redox-dependent regulation of kinase signalling

The small, obscure group of selenoprotein oxidoreductases and the huge clan of kinases, the workhorses of cellular signalling, are rarely discussed together. Focusing on selenoproteins of unknown structures, we predict a thioredoxin-like fold for the Selenoprotein N (SelN) family and use the structure to rationalise effects of the muscular myopathy-linked mutations in the gene coding SelN. Discussing the recent prediction of a protein kinase-like domain in the Selenoprotein O (SelO), we reiterate evidence for an oxidoreductase function alongside the predicted kinase domain. Thus, we propose that SelO, the strongly conserved kinase-cum-tentative-oxidoreductase may reflect oxidoreductase regulation of kinase networks. Also, we use bibliometric and systems biology approach to explore the kinase–selenoprotein relationships that begin to emerge from the literature. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).