LHPP:Mg2+ dimer hydrolyses PPi

Stable Identifier
R-HSA-6788912
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Inorganic pyrophosphate (PPi) is continuously produced as a result of ATP-utilising biosynthesis of protein, RNA, and DNA. Inorganic pyrophosphatase (PPase) catalyses the hydrolysis of PPi into two orthophosphates (Pi) thereby minimizing the cellular level of PPi and driving otherwise reversible reactions in the direction of PPi generation. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a dimeric protein, binding a Mg2+ in each subunit which can mediate the hydrolysis of PPi to 2xPi (Yokoi et al. 2003, Koike et al. 2006). LHPP is expressed in thyrocytes, located in the cytosol and nucleoplasm. In addition, LHPP is more prominently expressed in hyperfunctional states of the thyroid, such as in Graves disease and autonomously functional thyroid nodule (AFTN) (Koike et al. 2006).
More recent work indicates that LHPP acts as well to dephosphorylate phosphohistidine residues, that variants of it may be associated with suceptibilty to depression, and that it may be a tumor suppressor (reviewed in Gohla 2019), although without the molecular detail needed for a Reactome annotation.

Literature References
PubMed ID Title Journal Year
30030002 Do metabolic HAD phosphatases moonlight as protein phosphatases?

Gohla, A

Biochim Biophys Acta Mol Cell Res 2019
12801912 Molecular cloning of a cDNA for the human phospholysine phosphohistidine inorganic pyrophosphate phosphatase

Yokoi, F, Hiraishi, H, Izuhara, K

J. Biochem. 2003
16430861 Expression of new human inorganic pyrophosphatase in thyroid diseases: its intimate association with hyperthyroidism

Koike, E, Toda, S, Yokoi, F, Izuhara, K, Koike, N, Itoh, K, Miyazaki, K, Sugihara, H

Biochem. Biophys. Res. Commun. 2006
Participants
Output
Participates
Catalyst Activity

inorganic diphosphatase activity of LHPP:Mg2+ dimer [cytosol]

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