Pgam5 has been shown to lack phosphoglycerate mutase activity and possess serine/threonine phosphatase activity (FBrf0208569). Although there is no experimental evidence for substrate specificity of Pgam5-2, it has been group with Pgam5 as it shares conserved motifs and is thought to have been derived from the Pgam5 gene by retroposition (FBrf0225512).

Although Ssu72 exhibits very low primary sequence identity with proteins from any of the cysteine-based phosphatase family, except the existence of the Cys-X5-Arg active site motif, the fold of the core domain is highly identical with that of low- molecular-mass protein tyrosine phosphatases (FBrf0213130). It has been grouped with UNCLASSIFIED SERINE/THREONINE PHOSPHATASES as it dephosphorylates RNA polymerase II CTD Ser-5.