InterPro domain: IPR013078

The histidine phosphatase superfamily is so named because catalysiscentres on a conserved His residue that is transiently phosphorylatedduring the catalytic cycle. Other conserved residues contribute to a'phosphate pocket' and interact with the phospho group of substratebefore, during and after its transfer to the His residue. Structure andsequence analyses show that different families contribute differentadditional residues to the 'phosphate pocket' and, more surprisingly,differ in the position, in sequence and in three dimensions, of acatalytically essential acidic residue. The superfamily may be dividedinto two main branches. The relationship between the two branches isnot evident by (PSI-)BLAST but is clear from more sensitive sequencesearches and structural comparisons [ 1 ].

The larger clade-1 contains a wide variety of catalytic functions, the best known being fructose 2,6-bisphosphatase (found in a bifunctional protein with 2-phosphofructokinase) and cofactor-dependent phosphoglycerate mutase. The latter is an unusual example of a mutase activity in the superfamily: the vast majority of members appear to be phosphatases. The bacterial regulatory protein phosphatase SixA is also in clade-1 and has a minimal, and possible ancestral-like structure, lacking the large domain insertions that contribute to binding of small molecules in clade-1 members.

1. The histidine phosphatase superfamily: structure and function. Biochem. J. 409, 333-48