The proteins listed below share a common architecture with a protein kinase homology domain (see <PDOC00100>) followed by an ~135-residue globular kinase-extension nuclease (KEN) domain made of eight helices (see <PDB:2RIO>) [1]:

• Mammalian 2-5A-dependent RNase or RNase L (EC 3.1.26.-), an interferon- induced enzyme implicated in both the molecular mechanisms of interferon action and the fundamental control of RNA stability. 2-5A-dependent RNase is a unique enzyme in that it requires 2-5A, unusual oligoadenylates with 2',5'-phosphodiester linkages. RNase L is catalytically active only after binding to an unusual activator molecule containing a 5'-phosphorylated 2', 5'-linked oligoadenylate (2-5A), in the N-terminal half. RNase L consists of three domains, namely the N-terminal ankyrin repeat domain (see <PDOC50088>), the protein kinase homology domain, and the C-terminal KEN domain [2,3,4].
• Eukaryotic Ire1/Ern1, an ancient transmembrane sensor of endoplasmic reticulum (ER) stress with dual protein kinase and ribonuclease activities. In repsonse to ER stress Ire1/Ern1 catalyzes the splicing of target mRNAs in a spliceosome-independent manner. Ire1/Ern1 is a type 1 transmembrane receptor consisting of an N-terminal ER luminal domain, a transmembrane segment and a cytoplasmic region. The cytoplasmic region encompasses a protein kinase domain followed by a C-terminal KEN domain [1,5].

The dimerization of the kinase domain activates the ribonuclease function of the KEN domain [1].

The profile we developed covers the entire KEN domain.