A family of bacterial and eukaryotic endonucleases share the following characteristics: they act on both DNA and RNA, cleave double-stranded and single-stranded nucleic acids and require a divalent ion such as magnesium for their activity. A histidine has been shown []to be essential for the activity of the Serratia marcescens nuclease. This residue is located in a conserved region which also contains an aspartic acid residue that could be implicated in the binding of the divalent ion.This entry represents the nuclease/phosphodiesterase domain found in proteins from bacteria and eukaryotes, including ENPP1-3, mitochondrial Endonuclease G and Nuclease EXOG from animals, venom phosphodiesterases and related proteins.ENPP1 is a nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels []. It preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP and UTP to their corresponding monophosphates with release of pyrophosphate, as well as diadenosine polyphosphates, and also 3',5'-cAMP to AMP [, , , ]. ENPP2, also known as autotaxin, is a secreted lysophospholipase D that hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids [, ]. ENPP3 metabolizes extracellular nucleotides, including ATP, GTP, UTP and CTP [].Endonuclease G and EXOG act on DNA, preferentially double-stranded 5-hydroxymethylcytosine (5hmC)-modified DNA []and supercoiled DNA, a preference for single-stranded DNA and 5'-3' exonuclease activity [], respectively.
