Pathways & interactions
Histidine phosphatase superfamily (IPR029033)
Short name: His_PPase_superfam
- Histidine phosphatase superfamily, clade-2 (IPR000560)
- Fructose-2,6-bisphosphatase (IPR003094)
- Phosphohistidine phosphatase SixA (IPR004449)
- Phosphoglycerate mutase 1 (IPR005952)
- Lipopolysaccharide core heptose(II)-phosphate phosphatase (IPR011310)
- PRIB5 (IPR012398)
- Histidine phosphatase superfamily, clade-1 (IPR013078)
- Transcription factor TFIIIC subunit Tfc7/tau55 (IPR014623)
- RNase H, phosphoglycerate mutase domain-containing (IPR014636)
- Agropine synthesis reductase (IPR015845)
- Histidine acid phosphatase, eukaryotic (IPR016274)
- Uncharacterised conserved protein UCP036920, phosphoglycerate mutase, plant X4/Y4 (IPR017070)
- Alpha-ribazole phosphatase, CobC (IPR017578)
- Phosphomutase MSMEG4193, putative (IPR022492)
- Phosphoglycerate mutase, GpmB, probable (IPR023086)
- Venom acid phosphatase Acph-1 (IPR029630)
- Histidine acid phosphatase, VIP1 family (IPR037446)
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].