InterPro: IPR020583 Inositol monophosphatase, metal-binding site

It has been shown that several proteins share two sequence motifs [1]. Two of these proteins, vertebrate and plant inositol monophosphatase (EC:3.1.3.25), and vertebrate inositol polyphosphate 1-phosphatase (EC: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 [3].

This entry represents the metal-binding site found within the inositol monophosphatase family of proteins. It is suggested [1] that these proteins may act by enhancing the synthesis or degradation of phosphorylated messenger molecules. The signature pattern of this entry contains the aspartic and threonine residues involved in binding a metal ion [4].