Presence of a basic amino acid residue at either position 66 or 122 is a condition for enzymic activity in the ribonuclease superfamily.

Some members of the ribonuclease superfamily differ at more than 50% of the amino acid positions. Although the three-dimensional structures probably are very similar and the active-site residues have been conserved, other substrate-binding regions have changed considerably. Several proteins in the superfamily are active ribonucleases while other exhibit practically no enzymic activity. The presence of a basic residue at either position 66 or 122 appears to be a condition for ribonuclease activity.