IUBMB Enzyme Nomenclature


Accepted name: phosphohistidine phosphatase

Reaction: a [protein]-N-phospho-L-histidine + H2O = a [protein]-L-histidine + phosphate

Other name(s): PHPT1 (gene name); protein histidine phosphatase; PHP

Systematic name: [protein]-N-phospho-L-histidine phosphohydrolase

Comments: This eukaryotic enzyme dephosphorylates phosphorylated histidine residues within proteins and peptides. The enzyme acts on phosphate groups attached to both the pros- and tele-nitrogen atoms, but the pros- position is somewhat preferred (by a factor of two at the most) [4]. The substrate specificity depends on the amino acid sequence or structural context of the phosphohistidine in a phosphoprotein. The enzyme is also active on free phosphoramidate [1,4] and peptide-bound phospholysine [5].

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:


1. Ek, P., Pettersson, G., Ek, B., Gong, F., Li, J.P. and Zetterqvist, O. Identification and characterization of a mammalian 14-kDa phosphohistidine phosphatase. Eur. J. Biochem. 269 (2002) 5016-5023. [PMID: 12383260]

2. Klumpp, S., Hermesmeier, J., Selke, D., Baumeister, R., Kellner, R. and Krieglstein, J. Protein histidine phosphatase: a novel enzyme with potency for neuronal signaling. J Cereb Blood Flow Metab 22 (2002) 1420-1424. [PMID: 12468887]

3. Baumer, N., Maurer, A., Krieglstein, J. and Klumpp, S. Expression of protein histidine phosphatase in Escherichia coli, purification, and determination of enzyme activity. Methods Mol Biol 365 (2007) 247-260. [PMID: 17200567]

4. Attwood, P.V., Ludwig, K., Bergander, K., Besant, P.G., Adina-Zada, A., Krieglstein, J. and Klumpp, S. Chemical phosphorylation of histidine-containing peptides based on the sequence of histone H4 and their dephosphorylation by protein histidine phosphatase. Biochim. Biophys. Acta 1804 (2010) 199-205. [PMID: 19836471]

5. Ek, P., Ek, B. and Zetterqvist, O. Phosphohistidine phosphatase 1 (PHPT1) also dephosphorylates phospholysine of chemically phosphorylated histone H1 and polylysine. Ups J Med Sci 120 (2015) 20-27. [PMID: 25574816]

[EC created 2016]

Return to EC 3.9.1 home page
Return to EC 3.9 home page
Return to EC 3 home page
Return to Enzymes home page
Return to IUBMB Biochemical Nomenclature home page