Nucleoside Triphosphate Pyrophosphohydrolase (EC 3.6.1.8) MazG-like domain found in mouse RS21-C6 protein and its homologs
RS21-C6 proteins, highly expressed in all vertebrate genomes and green plants, act as house-cleaning enzymes, removing 5-methyl dCTP (m5dCTP) in order to prevent gene silencing. They show significant sequence similarity to the dimeric 2-deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTP pyrophosphatase or dUTPase) and NTP-PPase MazG proteins. However, unlike typical tandem-domain MazG proteins, RS21-C6 contains a single MazG-like domain and functions as a tetramer (a dimer of dimers) with a typical four-helical bundle. Divalent ions, such as Mg2+, are required for its pyrophosphatase activity. This family also includes a pyrophosphatase from Archaeoglobus fulgidus (Af1178). Although its biological role remains unclear, Af1178 shows significant sequence similarity to the mouse RS21-C6 protein.
Jiyao W et al.(2023). "The conserved domain database in 2023.",