Histidine phosphatase superfamily (IPR029033)

Short name: His_PPase_superfam

Family relationships


The histidine phosphatase superfamily is a large and functionally diverse group of proteins. They share a conserved catalytic core centred on a histidine which becomes phosphorylated during the course of the reaction. The superfamily is mainly composed of phosphatases, but the best-studied member is dPGM (cofactor-dependent phosphoglycerate mutase). The superfamily contains two branches sharing very limited sequence similarity: histidine phosphatase clade-1 and clade-2 [PMID: 18092946].

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.

The smaller clade-2 is composed mainly of acid phosphatases and phytases. Acid phosphatases are a heterogeneous group of proteins that hydrolyse phosphate esters, optimally at low pH. The catalytic functions of these proteins include phytase, glucose-1-phosphatase and multiple inositol polyphosphate phosphatase. Fungal phytases are histidine acid phosphatases that catalyze the hydrolysis of phytate (myo-inositol hexakisphosphate) to myo-inositol and inorganic phosphate [PMID: 8387447, PMID: 25132310].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.