Structural domains comprising this superfamily share the structure of the KEN domain found in Mammalian 2-5A-dependent RNase or RNase L, an interferon-induced enzyme implicated in molecular mechanisms of interferon action and control of RNA stability, and the eukaryotic Ire1/Ern1, an ancient transmembrane sensor of ER-stress which shows dual protein kinase and ribonuclease activities. Both enzymes share a common architecture with a protein kinase homology domain followed by an approximately 135-residue long globular kinase-extension nuclease (KEN) domain made of eight helices. Their KEN domain is responsible for the ribonuclease activity characteristic of both enzymes PMID:18191223.