F
IPR020552

Inositol monophosphatase, lithium-sensitive

InterPro entry
Short nameInositol_monoPase_Li-sen
family relationships

Description

It has been shown that several proteins share two sequence motifs
[1]
. Two of these proteins, vertebrate and plant inositol monophosphatase (
3.1.3.25
), and vertebrate inositol polyphosphate 1-phosphatase (
3.1.3.57
), are enzymes of the inositol phosphate second messenger signalling pathway, and share similar enzyme activity. Both enzymes exhibit an absolute requirement for metal ions (Mg2 is preferred), and their amino acid sequences contain a number of conserved motifs, which are also shared by several other proteins related to MPTASE (including products of fungal QaX and qutG, bacterial suhB and cysQ, and yeast hal2)
[2]
. The function of the other proteins is not yet clear, but it is suggested that they may act by enhancing the synthesis or degradation of phosphorylated messenger molecules
[1]
.

Structural analysis of these proteins has revealed a common core of 155 residues, which includes residues essential for metal binding and catalysis. An interesting property of the enzymes of this family is their sensitivity to Li+. The targets and mechanism of action of Li+ are unknown, but overactive inositol phosphate signalling may account for symptoms of manic depression
[5]
.

An interesting property of the enzymes of this family is their sensitivity to Li+ at levels achieved in patients undergoing therapy for manic depression. The targets and mechanism of action of Li+ are unknown, but overactive inositol phosphate signalling may account for symptoms of the disease
[5, 3]
. It has been proposed that these Li+-sensitive proteins could represent targets for Li+ in manic depressive disease
[2, 3, 4]
.

References

1.Diverse proteins homologous to inositol monophosphatase. Neuwald AF, York JD, Majerus PW. FEBS Lett. 294, 16-8, (1991). View articlePMID: 1660408

2.Definition of a metal-dependent/Li(+)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure. York JD, Ponder JW, Majerus PW. Proc. Natl. Acad. Sci. U.S.A. 92, 5149-53, (1995). View articlePMID: 7761465

3.High-resolution structure of myo-inositol monophosphatase, the putative target of lithium therapy. Gill R, Mohammed F, Badyal R, Coates L, Erskine P, Thompson D, Cooper J, Gore M, Wood S. Acta Crystallogr. D Biol. Crystallogr. 61, 545-55, (2005). View articlePMID: 15858264

4.A human myo-inositol monophosphatase gene (IMPA2) localized in a putative susceptibility region for bipolar disorder on chromosome 18p11.2: genomic structure and polymorphism screening in manic-depressive patients. Sjoholt G, Gulbrandsen AK, Lovlie R, Berle JO, Molven A, Steen VM. Mol. Psychiatry 5, 172-80, (2000). View articlePMID: 10822345

5.Neural and developmental actions of lithium: a unifying hypothesis. Berridge MJ, Downes CP, Hanley MR. Cell 59, 411-9, (1989). View articlePMID: 2553271

GO terms

molecular function

  • None

cellular component

  • None

Cross References

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