Phosphatase Subfamily LHPP

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Phosphatase Classification: Fold HAD: Superfamily HAD: Family NagD: Subfamily LHPP

LHPP is a protein histidine phosphatase conserved in holozoan.

Evolution

LHPP is found across holozoan. Human has two members of this subfamily, LHPP (lysine histidine pyrophosphate phosphatase) and HDHD2 (Haloacid Dehalogenase-like Hydrolase Domain containing 2). Distinct HDHD2 and LHPP genes are found as single copies in most animals, though Drosophila lacks LHPP and sea urchin has an additional HDHD2 degenerated into a pseudogene with frameshift.

Several fungi and oomycetes and a small number of bacteria have genes like HDHD2 in sequence, but it is uncertain whether they are true orthologs of HDHD2.

Domain

LHPP proteins consist of a single HAD domain with little flanking sequence.

Function

LHPP from cow was shown to dephosphorylate succinic thiokinase and nucleoside diphosphate kinase autophosphorylated at His residues. LHPP also has activity against free phospho-lysine and phospho-histidine amino acids [1]. HDHD2 has not been experimentally studied.

References

  1. Hiraishi H, Yokoi F, and Kumon A. Bovine liver phosphoamidase as a protein histidine/lysine phosphatase. J Biochem. 1999 Aug;126(2):368-74. DOI:10.1093/oxfordjournals.jbchem.a022459 | PubMed ID:10423531 | HubMed [Hiraishi]