asp1 (SPCC1672.06c; UniProt O74429) is the fission yeast PPIP5K/Vip1, a bifunctional inositol pyrophosphate enzyme. Its N-terminal ATP-grasp kinase domain phosphorylates the 1-position of 5-IP7, its preferred substrate, to give 1,5-IP8, and more slowly IP6 to 1-IP7. Its C-terminal histidine-acid-phosphatase-like domain specifically removes the 1-diphosphate of 1-IP7 and 1,5-IP8. That domain carries a [2Fe-2S] cluster which inhibits its activity, and inorganic phosphate antagonises it, so Asp1 sets cellular IP8 levels. IP8 controls phosphate homeostasis by promoting precocious termination of the lncRNAs that repress pho1, pho84 and tgp1. Asp1-generated IPPs also tune microtubule dynamics, bipolar spindle formation, chromosome segregation and polarised growth.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000828 inositol hexakisphosphate kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of IP6 kinase activity for the PPIP5K/Vip1 family; Asp1 phosphorylates IP6 (at position 1). Supporting Evidence: PMID:35536002 Reaction of Asp1 kinase with IP6 and ATP resulted in both IP6 phosphorylation to 1-IP7 and hydrolysis of the ATP Ξ³-phosphate |
| GO:0000828 inositol hexakisphosphate kinase activity | IDA PMID:25254656 The Vip1 inositol polyphosphate kinase family regulates pola... | ACCEPT | Summary: In vitro kinase assays of Asp1 variants show inositol pyrophosphate synthesis by the N-terminal kinase domain. Supporting Evidence: PMID:25254656 our analysis of the in vitro kinase activities of various S. pombe Asp1 variants demonstrated that the C-terminal phosphatase-like domain of the dual domain Vip1 protein negatively affects the inositol pyrophosphate output of the N-terminal kinase domain |
| GO:0000828 inositol hexakisphosphate kinase activity | IDA PMID:36468882 Structures of Fission Yeast Inositol Pyrophosphate Kinase As... | ACCEPT | Summary: Structures of the Asp1 kinase domain bound to IP6, 5-IP7 and 1,5-IP8 support its kinase activity on IP6. Supporting Evidence: PMID:36468882 IP8 dynamics are determined by Asp1, a bifunctional enzyme consisting of an N-terminal kinase domain and a C-terminal pyrophosphatase domain that catalyze IP8 synthesis and catabolism, respectively. |
| GO:0000829 diphosphoinositol pentakisphosphate kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Asp1 phosphorylates 5-IP7 (diphosphoinositol pentakisphosphate) to 1,5-IP8, its preferred reaction. Supporting Evidence: PMID:35536002 reaction of Asp1 kinase with 5-IP7 is 22-fold faster than with IP6 |
| GO:0005524 ATP binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ATP is the kinase cosubstrate; ATP-bound structures exist. Subsidiary. Supporting Evidence: PMID:36468882 IP8 dynamics are determined by Asp1, a bifunctional enzyme consisting of an N-terminal kinase domain and a C-terminal pyrophosphatase domain that catalyze IP8 synthesis and catabolism, respectively. |
| GO:0005634 nucleus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: Nuclear signal in the ORFeome screen; Asp1 is predominantly cytoplasmic. Reason: Not part of the core function. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt location mapping of the nuclear screen signal; no nuclear role known. Reason: Not part of the core function. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005737 cytoplasm | EXP PMID:10388810 Identification and characterization of Schizosaccharomyces p... | ACCEPT | Summary: Asp1 is cytoplasmic and not in any discrete structure. Supporting Evidence: PMID:10388810 Although Asp1p is not stably associated with the Arp2/3 complex nor localized in any discrete structure within the cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: Cytoplasmic signal in the ORFeome screen. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (cytoplasm), derived from the localisation screen. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005829 cytosol | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome YFP screen placed asp1 in the cytosol, consistent with a soluble metabolic enzyme. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of location; agrees with the localisation screen. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: UniProt location mapping to cytoskeleton. Asp1 regulates microtubule dynamics through its IPP products, but the original characterisation found it in no discrete cytoplasmic structure. Reason: A role affecting the cytoskeleton is not cytoskeletal location. Supporting Evidence: PMID:10388810 Although Asp1p is not stably associated with the Arp2/3 complex nor localized in any discrete structure within the cytoplasm PMID:25254656 Inositol pyrophosphates generated by Asp1 modulate MT dynamic parameters independent of the central +TIP EB1 and in a dose-dependent and cellular-context-dependent manner. |
| GO:0016887 ATP hydrolysis activity | IDA PMID:35536002 Activities and Structure-Function Analysis of Fission Yeast ... | KEEP AS NON CORE | Summary: The Asp1 kinase domain hydrolyses the ATP gamma-phosphate as an unproductive side reaction, comparable to IP6 phosphorylation and suppressed with 5-IP7 as substrate. Real but not physiological. Reason: Side reaction of the kinase. Supporting Evidence: PMID:35536002 Reaction of Asp1 kinase with IP6 and ATP resulted in both IP6 phosphorylation to 1-IP7 and hydrolysis of the ATP Ξ³-phosphate PMID:35536002 reaction of Asp1 kinase with 5-IP7 is 22-fold faster than with IP6 |
| GO:0023052 signaling | NAS GO_REF:0000051 | KEEP AS NON CORE | Summary: Inositol pyrophosphate signalling; vague, but the more specific processes are annotated. Supporting Evidence: PMID:31276588 Failure to synthesize IP8 (via Asp1 IPP kinase mutation) results in pho1 hyper-repression. |
| GO:0030643 intracellular phosphate ion homeostasis | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA mapping; supported by the IMP. Supporting Evidence: PMID:31276588 Failure to synthesize IP8 (via Asp1 IPP kinase mutation) results in pho1 hyper-repression. |
| GO:0030643 intracellular phosphate ion homeostasis | IMP PMID:31276588 Inositol pyrophosphates impact phosphate homeostasis via mod... | ACCEPT | Summary: IP8 made by Asp1 controls the PHO regulon: loss of kinase activity hyper-represses pho1, and loss of pyrophosphatase activity de-represses it through lncRNA termination. Supporting Evidence: PMID:31276588 Failure to synthesize IP8 (via Asp1 IPP kinase mutation) results in pho1 hyper-repression. PMID:31276588 Increasing IP8 (via Asp1 IPP pyrophosphatase mutation) de-represses the PHO regulon |
| GO:0032958 inositol phosphate biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference; consistent. Supporting Evidence: PMID:35536002 reaction of Asp1 kinase with 5-IP7 is 22-fold faster than with IP6 |
| GO:0032958 inositol phosphate biosynthetic process | IDA PMID:25254656 The Vip1 inositol polyphosphate kinase family regulates pola... | ACCEPT | Summary: Asp1 generates inositol pyrophosphates. Supporting Evidence: PMID:25254656 Inositol pyrophosphates generated by Asp1 modulate MT dynamic parameters independent of the central +TIP EB1 and in a dose-dependent and cellular-context-dependent manner. |
| GO:0032958 inositol phosphate biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA mapping; consistent. Supporting Evidence: PMID:35536002 reaction of Asp1 kinase with 5-IP7 is 22-fold faster than with IP6 |
| GO:0033857 5-diphosphoinositol pentakisphosphate 1-kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of 5-IP7 1-kinase activity; the defining PPIP5K reaction. Supporting Evidence: PMID:35536002 reaction of Asp1 kinase with 5-IP7 is 22-fold faster than with IP6 |
| GO:0033857 5-diphosphoinositol pentakisphosphate 1-kinase activity | IDA PMID:26422458 Asp1 from Schizosaccharomyces pombe binds a [2Fe-2S](2+) clu... | ACCEPT | Summary: Direct characterisation of Asp1 as a bifunctional IPP kinase/1-pyrophosphatase. Supporting Evidence: PMID:26422458 The phosphatase activity is exquisitely specific: it hydrolyzes the 1-diphosphate from just two members of the inositol pyrophosphate (PP-InsP) signaling family, namely, 1-InsP7 and 1,5-InsP8. |
| GO:0033857 5-diphosphoinositol pentakisphosphate 1-kinase activity | IDA PMID:27697865 Inositol Pyrophosphate Kinase Asp1 Modulates Chromosome Segr... | ACCEPT | Summary: Asp1 kinase activity is needed for bipolar spindle formation; the kinase domain generates IPPs. Supporting Evidence: PMID:27697865 We show that Asp1 kinase function is required for bipolar spindle formation. PMID:27697865 Vip1 enzymes are bifunctional: they consist of an IPP-generating kinase domain and a pyrophosphatase domain that uses such IPPs as substrates. |
| GO:0043647 inositol phosphate metabolic process | IMP PMID:25254656 The Vip1 inositol polyphosphate kinase family regulates pola... | ACCEPT | Summary: Asp1 controls cellular IPP levels. Supporting Evidence: PMID:25254656 Inositol pyrophosphates generated by Asp1 modulate MT dynamic parameters independent of the central +TIP EB1 and in a dose-dependent and cellular-context-dependent manner. |
| GO:0051516 regulation of bipolar cell growth | IMP PMID:25254656 The Vip1 inositol polyphosphate kinase family regulates pola... | ACCEPT | Summary: asp1 disruption causes polarised-growth defects, and Vip1 kinases regulate polarised growth in fungi. Supporting Evidence: PMID:10388810 disruption of asp1(+) leads to altered morphology and growth properties at elevated temperatures and defects in polarized growth PMID:25254656 Inositol pyrophosphates generated by Asp1 modulate MT dynamic parameters independent of the central +TIP EB1 and in a dose-dependent and cellular-context-dependent manner. |
| GO:0051537 2 iron, 2 sulfur cluster binding | IDA PMID:26422458 Asp1 from Schizosaccharomyces pombe binds a [2Fe-2S](2+) clu... | ACCEPT | Summary: The pyrophosphatase domain binds a [2Fe-2S] cluster that inhibits its 1-phosphatase activity; a unique feature of Asp1. Supporting Evidence: PMID:26422458 The presence of a [2Fe-2S](2+) cluster in Asp1(371-920) was demonstrated by UV-visible absorption, resonance Raman spectroscopy, and electron paramagnetic resonance spectroscopy. |
| GO:0052723 inositol hexakisphosphate 1-kinase activity | IDA PMID:35536002 Activities and Structure-Function Analysis of Fission Yeast ... | ACCEPT | Summary: Asp1 kinase phosphorylates IP6 at position 1 to give 1-IP7. Supporting Evidence: PMID:35536002 Reaction of Asp1 kinase with IP6 and ATP resulted in both IP6 phosphorylation to 1-IP7 and hydrolysis of the ATP Ξ³-phosphate |
| GO:0052723 inositol hexakisphosphate 1-kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC/RHEA mapping; consistent. Supporting Evidence: PMID:35536002 Reaction of Asp1 kinase with IP6 and ATP resulted in both IP6 phosphorylation to 1-IP7 and hydrolysis of the ATP Ξ³-phosphate |
| GO:0052723 inositol hexakisphosphate 1-kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Transfer from S. cerevisiae VIP1; consistent. Supporting Evidence: PMID:35536002 Reaction of Asp1 kinase with IP6 and ATP resulted in both IP6 phosphorylation to 1-IP7 and hydrolysis of the ATP Ξ³-phosphate |
| GO:0052841 inositol bisdiphosphate tetrakisphosphate diphosphatase activity | IEA GO_REF:0000117 | TOO GENERAL | Summary: ARBA mapping to the broad inositol bisdiphosphate tetrakisphosphate diphosphatase; Asp1 specifically removes the 1-diphosphate of 1,5-IP8, which is annotated separately. Supporting Evidence: PMID:26422458 The phosphatase activity is exquisitely specific: it hydrolyzes the 1-diphosphate from just two members of the inositol pyrophosphate (PP-InsP) signaling family, namely, 1-InsP7 and 1,5-InsP8. |
| GO:0052843 inositol-1-diphosphate-2,3,4,5,6-pentakisphosphate diphosphatase activity | IDA PMID:25254656 The Vip1 inositol polyphosphate kinase family regulates pola... | ACCEPT | Summary: Pyrophosphatase domain activity on 1-IP7, inferred from domain analysis. Supporting Evidence: PMID:25254656 our analysis of the in vitro kinase activities of various S. pombe Asp1 variants demonstrated that the C-terminal phosphatase-like domain of the dual domain Vip1 protein negatively affects the inositol pyrophosphate output of the N-terminal kinase domain |
| GO:0052843 inositol-1-diphosphate-2,3,4,5,6-pentakisphosphate diphosphatase activity | IDA PMID:26422458 Asp1 from Schizosaccharomyces pombe binds a [2Fe-2S](2+) clu... | ACCEPT | Summary: The phosphatase specifically hydrolyses the 1-diphosphate of 1-IP7 and 1,5-IP8. Supporting Evidence: PMID:26422458 The phosphatase activity is exquisitely specific: it hydrolyzes the 1-diphosphate from just two members of the inositol pyrophosphate (PP-InsP) signaling family, namely, 1-InsP7 and 1,5-InsP8. |
| GO:0052843 inositol-1-diphosphate-2,3,4,5,6-pentakisphosphate diphosphatase activity | IDA PMID:35536002 Activities and Structure-Function Analysis of Fission Yeast ... | ACCEPT | Summary: The pyrophosphatase domain opposes net 1-position phosphorylation. Supporting Evidence: PMID:35536002 the activity of the C-terminal pyrophosphatase domain stifled net phosphorylation of the 1-position |
| GO:0052843 inositol-1-diphosphate-2,3,4,5,6-pentakisphosphate diphosphatase activity | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA mapping; consistent. Supporting Evidence: PMID:26422458 The phosphatase activity is exquisitely specific: it hydrolyzes the 1-diphosphate from just two members of the inositol pyrophosphate (PP-InsP) signaling family, namely, 1-InsP7 and 1,5-InsP8. |
| GO:0052846 inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 1-diphosphatase activity | IDA PMID:26422458 Asp1 from Schizosaccharomyces pombe binds a [2Fe-2S](2+) clu... | ACCEPT | Summary: 1,5-IP8 1-phosphatase activity. Supporting Evidence: PMID:26422458 The phosphatase activity is exquisitely specific: it hydrolyzes the 1-diphosphate from just two members of the inositol pyrophosphate (PP-InsP) signaling family, namely, 1-InsP7 and 1,5-InsP8. |
| GO:0052846 inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 1-diphosphatase activity | IDA PMID:27697865 Inositol Pyrophosphate Kinase Asp1 Modulates Chromosome Segr... | ACCEPT | Summary: Bifunctional enzyme with an IPP pyrophosphatase domain. Supporting Evidence: PMID:27697865 Vip1 enzymes are bifunctional: they consist of an IPP-generating kinase domain and a pyrophosphatase domain that uses such IPPs as substrates. |
| GO:0052846 inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 1-diphosphatase activity | IDA PMID:35536002 Activities and Structure-Function Analysis of Fission Yeast ... | ACCEPT | Summary: The pyrophosphatase domain catabolises IP8. Supporting Evidence: PMID:35536002 the activity of the C-terminal pyrophosphatase domain stifled net phosphorylation of the 1-position PMID:36468882 IP8 dynamics are determined by Asp1, a bifunctional enzyme consisting of an N-terminal kinase domain and a C-terminal pyrophosphatase domain that catalyze IP8 synthesis and catabolism, respectively. |
| GO:0070507 regulation of microtubule cytoskeleton organization | IMP PMID:25254656 The Vip1 inositol polyphosphate kinase family regulates pola... | ACCEPT | Summary: Asp1-generated IPPs modulate microtubule dynamics in a dose-dependent way. Supporting Evidence: PMID:25254656 Inositol pyrophosphates generated by Asp1 modulate MT dynamic parameters independent of the central +TIP EB1 and in a dose-dependent and cellular-context-dependent manner. |
| GO:0071545 inositol phosphate catabolic process | IDA PMID:25254656 The Vip1 inositol polyphosphate kinase family regulates pola... | ACCEPT | Summary: The C-terminal domain hydrolyses IPPs; inositol phosphate catabolism. Supporting Evidence: PMID:25254656 our analysis of the in vitro kinase activities of various S. pombe Asp1 variants demonstrated that the C-terminal phosphatase-like domain of the dual domain Vip1 protein negatively affects the inositol pyrophosphate output of the N-terminal kinase domain |
| GO:0110162 regulation of mitotic spindle elongation (spindle phase three) | IMP PMID:27697865 Inositol Pyrophosphate Kinase Asp1 Modulates Chromosome Segr... | ACCEPT | Summary: Asp1 kinase function is needed for bipolar spindle formation and accurate chromosome segregation. Supporting Evidence: PMID:27697865 We show that Asp1 kinase function is required for bipolar spindle formation. |
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