IPK1 (GSL1, YDR315C) encodes inositol-1,3,4,5,6-pentakisphosphate 2-kinase (EC 2.7.1.158), the enzyme that phosphorylates the axial 2-hydroxyl of Ins(1,3,4,5,6)P5 to produce inositol hexakisphosphate (IP6, phytate), the final step of the Plc1-Arg82-Ipk1 pathway from PI(4,5)P2 to IP6. Ipk1 is highly selective for IP5 and is the sole route to IP6 in yeast; ipk1 cells lack IP6 and accumulate IP5. Ipk1 was identified in a gle1 synthetic-lethal screen, and its nuclear IP6 product is required for efficient Gle1/Dbp5-dependent mRNA export and supplies the substrate for inositol pyrophosphate synthesis by Kcs1 and Vip1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: IEA from InterPro IPR009286 (inositol-pentakisphosphate 2-kinase family). Ipk1 uses ATP as phosphate donor (Km for ATP 62.8 uM), so ATP binding is correct, but it is a generic consequence of the kinase activity rather than an informative function. Supporting Evidence: PMID:10960485 Purified recombinant scIpk1 kinase activity is highly selective for IP(5) substrate file:yeast/IPK1/IPK1-uniprot.txt Reaction=1D-myo-inositol 1,3,4,5,6-pentakisphosphate + ATP = 1D-myo- |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (is_active_in nucleus) from PTN000374859 (Arabidopsis IPK1, human IPPK, and yeast IPK1 itself as donor). Consistent with yeast data placing Ipk1 in the nucleus, where its IP6 product supports Gle1-dependent mRNA export. Supporting Evidence: file:yeast/IPK1/IPK1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10390371}. PMID:10390371 The common downstream effects of mutations in each component were deficiencies in IP6 synthesis and messenger RNA export |
| GO:0005634 nucleus | IDA PMID:10390371 A phospholipase C-dependent inositol polyphosphate kinase pa... | ACCEPT | Summary: IDA from York et al. 1999 (the Gle1 synthetic-lethal screen paper identifying GSL1/IPK1); UniProt records nuclear localization from this paper. Supporting Evidence: file:yeast/IPK1/IPK1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10390371}. PMID:10390371 The common downstream effects of mutations in each component were deficiencies in IP6 synthesis and messenger RNA export |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0191), based on York et al. 1999. Supporting Evidence: file:yeast/IPK1/IPK1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10390371}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: RCA from YeastPathways PWY3O-402 (inositol phosphate biosynthesis), which places all steps in the cytosol by default. Yeast experimental data place Ipk1 in the nucleus; a cytosolic pool is not excluded, but the YeastCyc compartment is a pathway-level default rather than evidence for Ipk1. Supporting Evidence: file:yeast/IPK1/IPK1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10390371}. |
| GO:0032958 inositol phosphate biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000374859 for inositol phosphate biosynthetic process. Correct and core: Ipk1 performs the final step of IP6 (phytate) synthesis. Supporting Evidence: PMID:10960485 Production of IP(6) predominately occurs through phosphorylation of inositol 1,3,4,5,6-pentakisphosphate (IP(5)) by a 2-kinase. |
| GO:0032958 inositol phosphate biosynthetic process | IDA PMID:10960485 Biochemical and functional characterization of inositol 1,3,... | ACCEPT | Summary: IDA from Ives et al. 2000: recombinant Ipk1 phosphorylates Ins(1,3,4,5,6)P5 to IP6 with high selectivity. Supporting Evidence: PMID:10960485 Purified recombinant scIpk1 kinase activity is highly selective for IP(5) substrate |
| GO:0032958 inositol phosphate biosynthetic process | IMP PMID:10390371 A phospholipase C-dependent inositol polyphosphate kinase pa... | ACCEPT | Summary: IMP from York et al. 1999: ipk1 (gsl1) mutants are deficient in IP6 synthesis. Supporting Evidence: PMID:10390371 The common downstream effects of mutations in each component were deficiencies in IP6 synthesis and messenger RNA export |
| GO:0032958 inositol phosphate biosynthetic process | IMP PMID:10960485 Biochemical and functional characterization of inositol 1,3,... | ACCEPT | Summary: IMP from Ives et al. 2000: ipk1 null cells lack IP6 production, complemented by the S. pombe orthologue. Supporting Evidence: PMID:10960485 Cells lacking sc-IPK1 are deficient in IP(6) production |
| GO:0032958 inositol phosphate biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-402: Ipk1 catalyses the Ins(1,3,4,5,6)P5 to phytate step (EC 2.7.1.158). Correct. Supporting Evidence: file:yeast/IPK1/IPK1-uniprot.txt Reaction=1D-myo-inositol 1,3,4,5,6-pentakisphosphate + ATP = 1D-myo- |
| GO:0035299 inositol-1,3,4,5,6-pentakisphosphate 2-kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000374859 (donors Arabidopsis AtIPK1, Drosophila, S. pombe ipk1 and others). Correct; Ipk1 has direct biochemical evidence for the activity. Supporting Evidence: PMID:10960485 Purified recombinant scIpk1 kinase activity is highly selective for IP(5) substrate file:yeast/IPK1/IPK1-uniprot.txt DOMAIN: The EXKPK motif is conserved in inositol-pentakisphosphate 2- |
| GO:0035299 inositol-1,3,4,5,6-pentakisphosphate 2-kinase activity | IDA PMID:10960485 Biochemical and functional characterization of inositol 1,3,... | ACCEPT | Summary: IDA from Ives et al. 2000: purified recombinant scIpk1 phosphorylates IP5 to IP6 (Km 644 nM for IP5; kcat/Km 31,610 s-1 M-1). Core activity. Supporting Evidence: PMID:10960485 Purified recombinant scIpk1 kinase activity is highly selective for IP(5) substrate |
| GO:0035299 inositol-1,3,4,5,6-pentakisphosphate 2-kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA (InterPro IPR009286, RHEA:20313, EC 2.7.1.158). Correct mapping. Supporting Evidence: file:yeast/IPK1/IPK1-uniprot.txt Reaction=1D-myo-inositol 1,3,4,5,6-pentakisphosphate + ATP = 1D-myo- |
| GO:0035299 inositol-1,3,4,5,6-pentakisphosphate 2-kinase activity | IMP PMID:10960485 Biochemical and functional characterization of inositol 1,3,... | ACCEPT | Summary: IMP from Ives et al. 2000: ipk1 null cells are deficient in IP6 and catalytically inactive point mutants identify catalytic residues, so the in vivo IP5 2-kinase activity is Ipk1's. Supporting Evidence: PMID:10960485 Cells lacking sc-IPK1 are deficient in IP(6) production |
| GO:0035299 inositol-1,3,4,5,6-pentakisphosphate 2-kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-402 (EC 2.7.1.158). Correct. Supporting Evidence: file:yeast/IPK1/IPK1-uniprot.txt Reaction=1D-myo-inositol 1,3,4,5,6-pentakisphosphate + ATP = 1D-myo- |
| GO:0070481 nuclear-transcribed mRNA catabolic process, non-stop decay | IMP PMID:17660569 A genomic screen in yeast reveals novel aspects of nonstop m... | MARK AS OVER ANNOTATED | Summary: IMP from Wilson et al. 2007 (nonstop mRNA genomic screen): ipk1 deletion suppresses the his3-nonstop phenotype. The full text shows this is because ipk1 cells accumulate the substrate IP5 (the effect disappears in ipk1 ipk2 double mutants), and it explicitly rules out a separate function of Ipk1 in nonstop decay. Ipk1 itself therefore does not participate in non-stop decay; the phenotype is an indirect metabolic consequence of losing the IP5 2-kinase. Supporting Evidence: PMID:17660569 Therefore, these results suggest that the suppression phenotype that we observed in an ipk1 Ξ strain is a result of the accumulation of IP5 and not a second, unrelated function of Ipk1p. |
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Download this section (compressed HTML)Q: Is IP6 synthesis by Ipk1 compartmentalised (nuclear versus cytoplasmic pools), and how much of the IP6 used by Kcs1/Vip1 for inositol pyrophosphate synthesis is made in the nucleus?
Q: What is the molecular target through which accumulated IP5 in ipk1 cells inhibits nonstop mRNA decay?
Experiment: Express nucleus-excluded (NES-tagged) Ipk1 in ipk1 cells and measure IP6, PP-IP levels and mRNA export to test whether nuclear localization is required.
Inositol 1,3,4,5,6-pentakisphosphate 2-kinase; nuclear protein required for synthesis of 1,2,3,4,5,6-hexakisphosphate (phytate), which is integral to cell function; has 2 motifs conserved in other fungi; ipk1 gle1 double mutant is inviable; human IPPK can complement ipk1 null mutant
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