Inositol polyphosphate multikinase

UniProtKB accession:  P07250

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UniProtKB description:  Inositol phosphate kinase with both monophosphoinositol and diphosphoinositol polyphosphate synthase activities. Able to phosphorylate inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) on both the carbon-3 and carbon-6 positions to synthesize 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), and then to subsequently phosphorylate and convert either isomer of InsP4 to inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) (PubMed:10574768, PubMed:10683435, PubMed:11311242). Its predominant in vivo catalytic function is to convert Ins(1,4,5)P3 to Ins(1,4,5,6)P4 to Ins(1,3,4,5,6)P5 via 6- and 3-kinase activities (PubMed:15944147). It can also use Ins(1,3,4,5,6)P5 as a substrate and act as a diphosphoinositol polyphosphate synthase to generate two different isomers of PP-InsP4 (PubMed:11311242). Has also a role in transcription regulation. Forms a complex with ARG80, ARG81 and MCM1 (ArgR-MCM1), which coordinates the expression of arginine anabolic and catabolic genes in response to arginine. Recruits ARG80 and MCM21 to stabilize them (PubMed:10632874, PubMed:3298999, PubMed:8043104). Neither the kinase activity nor inositol phosphates are required for the formation of ArgR-MCM1 transcriptional complexes on DNA promoter elements and the control of arginine metabolism (PubMed:10720331, PubMed:11119723, PubMed:12828642, PubMed:22992733). In contrast, only the catalytic activity is required for PHO gene repression by phosphate and for NCR gene activation in response to nitrogen availability, indicating a role for inositol pyrophosphates in these controls (PubMed:12828642). Inositol polyphosphates may be involved in the regulation of chromatin remodeling of transcription (PubMed:12434012). Regulates nuclear mRNA export via inositol phosphate metabolism (PubMed:10390371, PubMed:10683435). Also has lipid kinase activity, transforming the lipid inositol phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) into phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) in the nucleus (PubMed:16123124). Its kinase activity is necessary for the propagation of most [PSI+] prion variants (PubMed:28923943).