asp1

UniProt ID: O74429
Organism: Schizosaccharomyces pombe 972h-
Review Status: DRAFT
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Gene Description

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.

Existing Annotations Review

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.

Core Functions

Inositol pyrophosphate 1-kinase domain: 5-IP7 -> 1,5-IP8 (preferred) and IP6 -> 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
  • PMID:35536002
    reaction of Asp1 kinase with 5-IP7 is 22-fold faster than with IP6
  • 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.

Fe-S-regulated inositol pyrophosphate 1-pyrophosphatase domain hydrolysing 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.
  • 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.
  • PMID:35536002
    the activity of the C-terminal pyrophosphatase domain stifled net phosphorylation of the 1-position

IP8 produced by Asp1 regulates the PHO regulon via lncRNA 3-prime processing/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

References

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