Function
ARG82 is an inositol phosphate kinase exhibiting both monophosphoinositol and diphosphoinositol polyphosphate synthase activities. It can phosphorylate inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) at both the carbon-3 and carbon-6 positions, generating inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) and inositol 1,4,5,6-tetrakisphosphate (Ins(1,4,5,6)P4). Subsequently, it further phosphorylates and converts either InsP4 isomer to inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5). Its primary in vivo catalytic function involves converting Ins(1,4,5)P3 to Ins(1,4,5,6)P4 and then to Ins(1,3,4,5,6)P5 through 6- and 3-kinase activities. Additionally, it can utilize Ins(1,3,4,5,6)P5 as a substrate, acting as a diphosphoinositol polyphosphate synthase to produce two distinct isomers of PP-InsP4. ARG82 also plays a role in transcription regulation. It forms a complex with ARG80, ARG81, and MCM1 (ArgR-MCM1), which orchestrates the expression of arginine anabolic and catabolic genes in response to arginine levels. ARG82 recruits ARG80 and MCM21, contributing to their stabilization. Notably, neither the kinase activity nor inositol phosphates are essential for the formation of ArgR-MCM1 transcriptional complexes on DNA promoter elements and the control of arginine metabolism. However, the catalytic activity is crucial for PHO gene repression by phosphate and for NCR gene activation in response to nitrogen availability, highlighting a role for inositol pyrophosphates in these regulatory mechanisms. Inositol polyphosphates may be involved in the regulation of chromatin remodeling during transcription. ARG82 regulates nuclear mRNA export through inositol phosphate metabolism. Moreover, it possesses lipid kinase activity, converting the lipid inositol phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) into phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) within the nucleus. Its kinase activity is essential for the propagation of most [PSI+] prion variants.