HEPNcontaining

HEPN-containing refers to proteins that possess the HEPN domain, a conserved ribonuclease domain found across bacteria, archaea, and eukaryotes. The name reflects its broad distribution in both higher organisms and microbes. The HEPN domain is generally a compact, predominantly helical fold that often functions as a dimer; catalytic activity is associated with conserved residues within a short motif, frequently described as an RX4-6H pattern, with the histidine essential for RNase activity.

Functional roles vary: many HEPN-containing proteins act as RNA endonucleases and are implicated in RNA metabolism, antiviral defense, and toxin–antitoxin systems. In bacteria, they can participate in stress responses or programmed cell death under phage infection or other stresses. In eukaryotes, HEPN-containing proteins have been linked to RNA processing and innate immune pathways, though the specific functions can be diverse and context-dependent.

Genomic organization is variable: HEPN domains occur as standalone modules or are fused to other catalytic or regulatory domains, reflecting functional diversification. Widespread phyletic distribution suggests ancient origins with subsequent expansion and specialization.

Research status: Characterization of HEPN domains includes structural analyses and mutational studies that identify residues important for catalysis and dimerization; substrate specificities and regulatory mechanisms remain active areas of investigation. The HEPN domain is a notable example of a ribonuclease fold with broad biological significance across domains of life.