InterPro domain: IPR005522

Inositol phosphates (IPs) act as signalling messengers to regulate various cellular processes such as growth. This entry includes a group of inositol polyphosphate kinase, including inositol polyphosphate multikinase Arg82 and Inositol hexakisphosphate/inositol heptakisphosphate kinase Kcs1 from budding yeast. They play important roles in vacuole biogenesis and the cell's response to certain environmental stresses. The kinase activity of Arg82 and Kcs1 is required for the production of soluble inositol phosphates [ 1 ]. Independently of its catalytic activity, Arg82 is crucial for assembling the Arg80-Mcm1 protein complex at the promoter region of genes involved in arginine metabolism [ 2 ].

This entry also includes human inositol hexakisphosphate kinase 1/2/3 (IP6K1/2/3)[ 2 ], inositol polyphosphate multikinase (IPMK) [ 3 ] and inositol-trisphosphate 3-kinase A/B/C (IP3KA/B/C) [ 4 ]. They are involved in inositol phosphate biosynthesis [ 5 ]. Independently of its catalytic activity, IPMK mediates the activation of mammalian target of rapamycin (mTOR) in response to essential amino acids [ 6 . Crystallographic analysis showed that the disordered domains of IPMK modulates its kinase activity [ 6 ].

1. Arg82p is a bifunctional protein whose inositol polyphosphate kinase activity is essential for nitrogen and PHO gene expression but not for Mcm1p chaperoning in yeast. Mol. Microbiol. 49, 457-68
2. Identification and characterization of a novel inositol hexakisphosphate kinase. J. Biol. Chem. 276, 39179-85
3. The human homolog of the rat inositol phosphate multikinase is an inositol 1,3,4,6-tetrakisphosphate 5-kinase. J. Biol. Chem. 277, 43836-43
4. Ins(1,4,5)P3 3-kinase-A overexpression induces cytoskeletal reorganization via a kinase-independent mechanism. Biochem. J. 414, 407-17
5. Inositol polyphosphate multikinase signaling in the regulation of metabolism. Ann. N. Y. Acad. Sci. 1271, 68-74
6. Crystallographic and kinetic analyses of human IPMK reveal disordered domains modulate ATP binding and kinase activity. Sci Rep 8, 16672