Vip1 is the budding-yeast diphosphoinositol pentakisphosphate kinase (PPIP5K), a large bifunctional cytoplasmic enzyme with an N-terminal ATP-grasp inositol pyrophosphate kinase domain and a C-terminal histidine-acid-phosphatase (phytase-like) domain. The kinase domain transfers a beta-phosphate to the 1-position of the inositol ring, converting InsP6 to 1-InsP7 and the Kcs1 product 5-InsP7 to 1,5-InsP8 ((PP)2-InsP4). The phosphatase domain hydrolyses the 1-diphosphate, preferring 1,5-InsP8, and is inhibited by inorganic phosphate, so that the balance of the two activities couples inositol pyrophosphate levels to phosphate availability. Vip1-generated inositol pyrophosphate is required for Pho81-dependent inhibition of the Pho80-Pho85 cyclin-CDK in the PHO phosphate-starvation response, and Vip1 also influences cortical actin organisation and growth.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000828 inositol hexakisphosphate kinase activity | IBA GO_REF:0000033 | TOO GENERAL | Summary: PAINT IBA (PTN000297581) for InsP6 kinase activity, seeded by Arabidopsis VIH1/VIH2, mouse/human PPIP5Ks, S. pombe Asp1 and Vip1 itself. Vip1 phosphorylates InsP6 at position 1; the general InsP6 kinase parent term is correct for this protein. Supporting Evidence: PMID:17412958 Vip1 and Asp1 acted as enzymes that encode inositol hexakisphosphate (IP6) and inositol heptakisphosphate (IP7) kinase activities |
| GO:0000828 inositol hexakisphosphate kinase activity | RCA GO_REF:0000123 | TOO GENERAL | Summary: YeastPathways RCA from the inositol phosphate biosynthesis pathway (PWY3O-402) for the InsP6 -> PP-InsP5 step. Matches experimental data for Vip1; the more precise 1-kinase term GO:0052723 is also annotated. Supporting Evidence: PMID:18981179 the VIP/PPIP5K enzymes convert inositol hexakisphosphate to 1/3-diphosphoinositol pentakisphosphate |
| GO:0000829 diphosphoinositol pentakisphosphate kinase activity | IDA PMID:17412958 A conserved family of enzymes that phosphorylate inositol he... | ACCEPT | Summary: IDA (Mulugu et al. 2007) for phosphorylation of PP-InsP5 (IP7) to (PP)2-InsP4. Consistent with the later structural assignment that Vip1 converts the Kcs1 product 5-InsP7 to 1,5-InsP8. Supporting Evidence: PMID:17412958 Vip1 and Asp1 acted as enzymes that encode inositol hexakisphosphate (IP6) and inositol heptakisphosphate (IP7) kinase activities PMID:18981179 1/3,5-(PP)2-IP4 is the isomeric structure of the bis-diphosphoinositol tetrakisphosphate that is synthesized by yeasts and mammals |
| GO:0000829 diphosphoinositol pentakisphosphate kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from ARBA00047220 and InterPro IPR037446 (PPIP5K family). Correct family-level transfer for Vip1, experimentally confirmed. Supporting Evidence: file:yeast/VIP1/VIP1-uniprot.txt Bifunctional inositol kinase that acts in concert with the |
| GO:0000829 diphosphoinositol pentakisphosphate kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-402) for the PP-InsP5 -> (PP)2-InsP4 step (EC 2.7.4.24). Correct for Vip1. Supporting Evidence: PMID:18981179 1/3,5-(PP)2-IP4 is the isomeric structure of the bis-diphosphoinositol tetrakisphosphate that is synthesized by yeasts and mammals |
| GO:0000830 inositol hexakisphosphate 4-kinase activity | IDA PMID:17412958 A conserved family of enzymes that phosphorylate inositol he... | REMOVE | Summary: IDA for InsP6 4-kinase activity from the 2007 discovery paper, which initially placed the new pyrophosphate at the 4/6 position. Positional analysis by HPLC and 2D NMR (Lin et al. 2009, same York laboratory) showed that yeast and mammalian Vip1/PPIP5Ks phosphorylate the 1/3 position in vitro and in vivo, and UniProt/Rhea record the reaction at position 1. Reason: Positional specificity contradicted by the definitive structural analysis; Vip1 is an InsP6 1-kinase, captured by GO:0052723. Supporting Evidence: PMID:18981179 we have determined that the mammalian and yeast VIP/PPIP5K family phosphorylates the 1/3-position of the inositol ring in vitro and in vivo |
| GO:0000831 inositol hexakisphosphate 6-kinase activity | IDA PMID:17412958 A conserved family of enzymes that phosphorylate inositol he... | REMOVE | Summary: IDA for InsP6 6-kinase activity from the 2007 discovery paper (4/6-position assignment). Superseded by NMR-based positional analysis showing 1/3-position phosphorylation by yeast Vip1. Reason: Contradicted by later definitive positional analysis; Vip1 is an InsP6 1-kinase (GO:0052723). Supporting Evidence: PMID:18981179 we have determined that the mammalian and yeast VIP/PPIP5K family phosphorylates the 1/3-position of the inositol ring in vitro and in vivo |
| GO:0005524 ATP binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from human PPIP5K1 (O43314) for ATP binding. Vip1 has an ATP-grasp kinase domain and its structure was solved with ADP bound, so the binding is real, but it is a cofactor-level property implied by the kinase activities. Reason: Correct but uninformative relative to the specific inositol pyrophosphate kinase activities. Supporting Evidence: PMID:39966396 The structure of ScVip1KD in complex with adenosine diphosphate revealed the typical ATP-grasp fold |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: HDA from the genome-wide GFP localisation screen (Huh et al. 2003), which placed Vip1-GFP in the cytoplasm. Consistent with a soluble inositol polyphosphate kinase. Supporting Evidence: PMID:14562095 Global analysis of protein localization in budding yeast. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0086 cytoplasm), itself based on the Huh et al. GFP data. Correct. Supporting Evidence: file:yeast/VIP1/VIP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for cytosol (PTN000297583, from human/mouse PPIP5Ks). Vip1 is a soluble cytoplasmic enzyme; cytosol is the appropriate refinement. Supporting Evidence: file:yeast/VIP1/VIP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA placing the inositol phosphate kinase reactions of PWY3O-402 in the cytosol. Consistent with the GFP data. Supporting Evidence: file:yeast/VIP1/VIP1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA from UniProt subcellular location (SL-0090 cytoskeleton), derived from the same high-throughput GFP screen. No targeted study shows Vip1 associated with actin or microtubule structures in S. cerevisiae; the genetic links to the Arp2/3 complex come mainly from S. pombe Asp1. Reason: Weak, screen-derived localisation; not part of the enzymatic core. Supporting Evidence: file:yeast/VIP1/VIP1-uniprot.txt Cytoplasm, cytoskeleton {ECO:0000269|PubMed:14562095}. |
| GO:0030643 intracellular phosphate ion homeostasis | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA IEA for intracellular phosphate ion homeostasis. Supported for Vip1 by the IMP data (Lee et al. 2007) showing that Vip1-derived inositol pyrophosphate is needed for the PHO starvation response, and by the Pi-sensitive balance of its kinase and phosphatase activities. Supporting Evidence: PMID:17412959 suggesting that Vip1 mediates synthesis of IP 7 relevant to the PHO system |
| GO:0030643 intracellular phosphate ion homeostasis | IMP PMID:17412959 Regulation of a cyclin-CDK-CDK inhibitor complex by inositol... | ACCEPT | Summary: IMP (Lee et al. 2007). Extracts from Pi-starved vip1 deletion cells fail to inactivate Pho80-Pho85 in a Pho81-dependent manner, and Pho4 stays cytoplasmic under starvation in vip1 cells. Supporting Evidence: PMID:17412959 The extract from kcs1 Ξ cells inactivated Pho80-Pho85 in a Pho81-dependent manner, whereas extract from vip1 Ξ cells did not, suggesting that Vip1 mediates synthesis of IP 7 relevant to the PHO system. |
| GO:0032958 inositol phosphate biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for inositol phosphate biosynthetic process (PTN000297581). Vip1 synthesises the inositol pyrophosphates 1-InsP7 and 1,5-InsP8. Supporting Evidence: PMID:18981179 the VIP/PPIP5K enzymes convert inositol hexakisphosphate to 1/3-diphosphoinositol pentakisphosphate |
| GO:0032958 inositol phosphate biosynthetic process | IDA PMID:17412958 A conserved family of enzymes that phosphorylate inositol he... | ACCEPT | Summary: IDA (Mulugu et al. 2007) - recombinant Vip1 synthesises inositol pyrophosphates from InsP6/InsP7. Supporting Evidence: PMID:17412958 Vip1 and Asp1 acted as enzymes that encode inositol hexakisphosphate (IP6) and inositol heptakisphosphate (IP7) kinase activities |
| GO:0032958 inositol phosphate biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA IEA for inositol phosphate biosynthetic process; correct for Vip1 (experimentally confirmed). Supporting Evidence: PMID:17412958 Vip1 and Asp1 acted as enzymes that encode inositol hexakisphosphate (IP6) and inositol heptakisphosphate (IP7) kinase activities |
| GO:0032958 inositol phosphate biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-402 inositol phosphate biosynthesis). Vip1 catalyses the pyrophosphate steps of this pathway; correct. Supporting Evidence: PMID:18981179 1/3,5-(PP)2-IP4 is the isomeric structure of the bis-diphosphoinositol tetrakisphosphate that is synthesized by yeasts and mammals |
| GO:0033857 5-diphosphoinositol pentakisphosphate 1-kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for 5-diphosphoinositol pentakisphosphate 1-kinase activity (5-InsP7 -> 1,5-InsP8). This is the most precise description of the Vip1 reaction acting on the Kcs1 product, consistent with the 1,5-(PP)2-IP4 structure determined for yeast. Supporting Evidence: PMID:18981179 1/3,5-(PP)2-IP4 is the isomeric structure of the bis-diphosphoinositol tetrakisphosphate that is synthesized by yeasts and mammals |
| GO:0051516 regulation of bipolar cell growth | ISS GO_REF:0000024 | REMOVE | Summary: ISS from S. pombe Asp1 (O74429), whose loss affects bipolar growth (growth at both cell tips) in fission yeast. S. cerevisiae grows by budding and has no bipolar tip-growth mode; no budding-yeast data support this process for Vip1. Reason: Taxon-inappropriate transfer of a fission-yeast growth-mode process to budding yeast. Supporting Evidence: file:yeast/VIP1/VIP1-uniprot.txt growth and modulates interphase microtubule cytoskeleton. Regulates |
| GO:0052723 inositol hexakisphosphate 1-kinase activity | EXP PMID:17412958 A conserved family of enzymes that phosphorylate inositol he... | ACCEPT | Summary: EXP (Mulugu et al. 2007) for InsP6 kinase activity; refined by Lin et al. 2009 to the 1/3 position. UniProt and Rhea (RHEA:37459) record InsP6 1-kinase activity; core kinase activity of Vip1. Supporting Evidence: PMID:17412958 Vip1 and Asp1 acted as enzymes that encode inositol hexakisphosphate (IP6) and inositol heptakisphosphate (IP7) kinase activities |
| GO:0052723 inositol hexakisphosphate 1-kinase activity | IDA PMID:18981179 Structural analysis and detection of biological inositol pyr... | ACCEPT | Summary: IDA (Lin et al. 2009) - HPLC and NMR analysis of products shows phosphorylation of InsP6 at the 1/3 position by yeast Vip1. Core activity. Supporting Evidence: PMID:18981179 the VIP/PPIP5K enzymes convert inositol hexakisphosphate to 1/3-diphosphoinositol pentakisphosphate |
| GO:0052723 inositol hexakisphosphate 1-kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA00088884, RHEA:37459). Correct mapping for Vip1. Supporting Evidence: file:yeast/VIP1/VIP1-uniprot.txt Reaction=1D-myo-inositol hexakisphosphate + ATP = 1-diphospho-1D-myo- |
| GO:0052724 inositol hexakisphosphate 3-kinase activity | IDA PMID:18981179 Structural analysis and detection of biological inositol pyr... | MARK AS OVER ANNOTATED | Summary: IDA (Lin et al. 2009) for InsP6 3-kinase. The study could not distinguish the 1 and 3 enantiomeric positions and reported '1/3-kinase'; the field and UniProt/Rhea assign the reaction to position 1, so the 3-kinase reading of the same data is an over-interpretation. Reason: Enantiomeric 1/3 ambiguity in the source; position 1 is the accepted assignment and is already annotated (GO:0052723). Supporting Evidence: PMID:18981179 VIP/PPIP5K family phosphorylates the 1/3-position of the inositol ring in vitro and in vivo |
| GO:0052841 inositol bisdiphosphate tetrakisphosphate diphosphatase activity | IDA PMID:39966396 A small signaling domain controls PPIP5K phosphatase activit... | ACCEPT | Summary: IDA (2025 structural/biochemical study) showing that the isolated ScVip1 phosphatase domain hydrolyses 1,5-InsP8 (its preferred substrate) back to 5-InsP7. Overrides the UniProt caution that the domain is inactive. Supporting Evidence: PMID:39966396 ScVip1PD specifically hydrolyzes 1,5-InsP8 using a conserved phytase active site. |
| GO:0052841 inositol bisdiphosphate tetrakisphosphate diphosphatase activity | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA IEA for inositol bisdiphosphate tetrakisphosphate diphosphatase; experimentally confirmed for Vip1. Supporting Evidence: PMID:39966396 ScVip1PD specifically hydrolyzes 1,5-InsP8 using a conserved phytase active site. |
| GO:0052841 inositol bisdiphosphate tetrakisphosphate diphosphatase activity | IMP PMID:39966396 A small signaling domain controls PPIP5K phosphatase activit... | ACCEPT | Summary: IMP from the same study (catalytic-loop RHR mutants of the phosphatase domain) supporting the 1,5-InsP8 phosphatase activity. Supporting Evidence: PMID:39966396 we replaced the catalytic loop residues Arg547, His548 and Arg551 in ScVip1PD |
| GO:0052843 inositol-1-diphosphate-2,3,4,5,6-pentakisphosphate diphosphatase activity | IDA PMID:31436531 Two bifunctional inositol pyrophosphate kinases/phosphatases... | ACCEPT | Summary: IDA from Zhu et al. 2019 (plant VIH paper that also assayed the S. cerevisiae Vip1 phosphatase domain); ScVip1-PD hydrolyses 1-InsP7 to InsP6, especially at low ATP. Supporting Evidence: PMID:31436531 We found that at low ATP concentrations the ScVip1 phosphatase activity predominates, releasing InsP6 |
| GO:0052843 inositol-1-diphosphate-2,3,4,5,6-pentakisphosphate diphosphatase activity | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA IEA for 1-InsP7 diphosphatase; experimentally supported for Vip1. Supporting Evidence: PMID:31436531 We found that at low ATP concentrations the ScVip1 phosphatase activity predominates, releasing InsP6 |
| GO:0052845 inositol-5-diphosphate-1,2,3,4,6-pentakisphosphate diphosphatase activity | IDA PMID:31436531 Two bifunctional inositol pyrophosphate kinases/phosphatases... | KEEP AS NON CORE | Summary: IDA from Zhu et al. 2019 showing ScVip1 phosphatase-domain hydrolysis of 5PP-InsP5 (inhibited by Pi). The domain prefers 1-diphosphates (1,5-InsP8 >> 5-InsP7 in the 2025 kinetics), so 5-InsP7 hydrolysis is a real but secondary in vitro activity. Reason: Demonstrated in vitro but a minor substrate relative to 1,5-InsP8/1-InsP7. Supporting Evidence: PMID:31436531 We found that 5PP-InsP5 hydrolysis by the isolated ScVip1 phosphatase domain is inhibited in the presence of 10 mM Pi |
| GO:0070507 regulation of microtubule cytoskeleton organization | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS from S. pombe Asp1 (O74429), where inositol pyrophosphate levels modulate interphase microtubule dynamics. No S. cerevisiae Vip1 data on microtubules exist; the transfer rests on a fission-yeast-specific phenotype. Reason: Downstream phenotype in another species, not shown for budding-yeast Vip1. Supporting Evidence: file:yeast/VIP1/VIP1-uniprot.txt growth and modulates interphase microtubule cytoskeleton. Regulates |
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Download this section (compressed HTML)Q: Which Vip1 product (1-InsP7 or 1,5-InsP8) is the physiological ligand of Pho81 and of SPX-domain proteins in budding yeast, and how is the kinase/phosphatase balance of Vip1 set in vivo by Pi?
Experiment: Compare PHO-pathway signalling and InsP7/InsP8 isomer profiles (capillary electrophoresis-MS) in vip1 kinase-dead versus phosphatase-dead (RH/AA) point mutants under Pi-replete and Pi-starved conditions.
Bifunctional inositol pyrophosphate kinase and phosphatase; contains two conserved catalytic motifs, a PPIP5K kinase domain that phosphorylates inositol hexakis- and heptakisphosphate, and a PPIP5K phosphatase domain that preferentially hydrolyzes, 1PP-InsP5 and 1,5-InsP8; unique GAF domain channels PPase substrates to the active site; IP7 levels decrease during starvation, suggesting a role in Pi homeostasis; may regulate the dimorphic switch and function of the cortical actin cytoskeleton
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