ppc1

UniProt ID: Q9USK7
Organism: Schizosaccharomyces pombe 972h-
Review Status: COMPLETE
Aliases:
SPCC4B3.18
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Gene Description

Phosphopantothenate--cysteine ligase (phosphopantothenoylcysteine synthetase, PPCS; EC 6.3.2.51/6.3.2.5) of fission yeast, encoded by SPCC4B3.18 (UniProt still names it 'Uncharacterized protein C4B3.18'). It condenses 4'-phosphopantothenate with L-cysteine to 4'-phosphopantothenoylcysteine, the second step of CoA biosynthesis. Ppc1 is essential: temperature-sensitive mutants (ts-537, T48I; ts-88, M209T) map in ppc1; ppc1-537 becomes auxotrophic for pantothenate at permissive temperature and has greatly reduced CoA and acetyl-CoA, histone hypoacetylation, failure to exit quiescence, mitotic chromosome-segregation defects and fragile DNA. GFP-tagged Ppc1 is distributed throughout the cell.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004632 phosphopantothenate--cysteine ligase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: PAINT IBA from PTN000265180 (donors human PPCS, S. cerevisiae Cab2, Arabidopsis and Drosophila PPCS, and S. pombe ppc1 itself through its IMP).
Reason: Core activity; inherited family function with target-level experimental grounding.
Supporting Evidence:
PMID:23091701
We isolated a novel S. pombe temperature-sensitive strain ppc1-537 mutated in the catalytic region of phosphopantothenoylcysteine synthetase (designated Ppc1), which is essential for CoA synthesis.
PMID:23091701
The mutant becomes auxotrophic to pantothenate at permissive temperature, displaying greatly decreased levels of CoA, acetyl-CoA and histone acetylation.
PMID:23091701
It is similar to human PPCS (amino acid identity 42%) and budding yeast Cab2 (identity 45%).
file:SCHPO/ppc1/ppc1-uniprot.txt
SIMILARITY: Belongs to the PPC synthetase family.
GO:0004632 phosphopantothenate--cysteine ligase activity
IEA
GO_REF:0000117 		ACCEPT
Summary: ARBA rule mapping to phosphopantothenate--cysteine ligase activity. Correct.
Reason: Agrees with phylogeny and S. pombe genetics.
Supporting Evidence:
file:SCHPO/ppc1/ppc1-uniprot.txt
SIMILARITY: Belongs to the PPC synthetase family.
GO:0004632 phosphopantothenate--cysteine ligase activity
IMP
PMID:23091701
Impaired coenzyme A synthesis in fission yeast causes defect... 		ACCEPT
Summary: ts mutations in the catalytic region of ppc1 cause pantothenate auxotrophy-like phenotypes and greatly reduced CoA, consistent with loss of PPCS activity (enzyme activity itself was not assayed in the abstract).
Reason: Curator IMP from full-text paper; loss-of-function plus strong homology to human PPCS/Cab2 support the activity.
Supporting Evidence:
PMID:23091701
We isolated a novel S. pombe temperature-sensitive strain ppc1-537 mutated in the catalytic region of phosphopantothenoylcysteine synthetase (designated Ppc1), which is essential for CoA synthesis.
PMID:23091701
The mutant becomes auxotrophic to pantothenate at permissive temperature, displaying greatly decreased levels of CoA, acetyl-CoA and histone acetylation.
PMID:23091701
It is similar to human PPCS (amino acid identity 42%) and budding yeast Cab2 (identity 45%).
GO:0005634 nucleus
HDA
PMID:16823372
ORFeome cloning and global analysis of protein localization ... 		KEEP AS NON CORE
Summary: ORFeome YFP screen detected ppc1 in the nucleus as well as the cytosol.
Reason: Whole-cell distribution; no nuclear role is known (nuclear effects of ppc1 mutants such as histone hypoacetylation are indirect consequences of low acetyl-CoA).
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein
GO:0005634 nucleus
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: PAINT IBA (PTN000265180) for nucleus from S. pombe ppc1 and a trypanosome PPCS.
Reason: Observed but not functionally relevant.
Supporting Evidence:
PMID:23091701
The GFP signals of both Ppc1 and Ptk1 were observed in the whole cell (figure 4e), whereas Acs1 was enriched in the nuclear chromatin.
GO:0005634 nucleus
IDA
PMID:23091701
Impaired coenzyme A synthesis in fission yeast causes defect... 		KEEP AS NON CORE
Summary: GFP-tagged Ppc1 seen throughout the cell, including the nucleus.
Reason: Direct observation, non-core.
Supporting Evidence:
PMID:23091701
The GFP signals of both Ppc1 and Ptk1 were observed in the whole cell (figure 4e), whereas Acs1 was enriched in the nuclear chromatin.
GO:0005634 nucleus
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: UniProt SubCell mapping of 'Nucleus' (from ORFeome).
Reason: As for the HDA row.
Supporting Evidence:
file:SCHPO/ppc1/ppc1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus
GO:0005737 cytoplasm
IBA
GO_REF:0000033 		ACCEPT
Summary: PAINT IBA (PTN000265180) for cytoplasm.
Reason: Correct; CoA synthesis is cytosolic.
Supporting Evidence:
PMID:23091701
The GFP signals of both Ppc1 and Ptk1 were observed in the whole cell (figure 4e), whereas Acs1 was enriched in the nuclear chromatin.
GO:0005737 cytoplasm
IDA
PMID:23091701
Impaired coenzyme A synthesis in fission yeast causes defect... 		ACCEPT
Summary: GFP-tagged Ppc1 expressed from its native promoter is distributed through the cytoplasm.
Reason: Direct S. pombe evidence.
Supporting Evidence:
PMID:23091701
The GFP signals of both Ppc1 and Ptk1 were observed in the whole cell (figure 4e), whereas Acs1 was enriched in the nuclear chromatin.
GO:0005737 cytoplasm
IEA
GO_REF:0000044 		ACCEPT
Summary: UniProt SubCell mapping of 'Cytoplasm'. Correct.
Reason: Consistent with experimental data.
Supporting Evidence:
file:SCHPO/ppc1/ppc1-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus
GO:0005829 cytosol
HDA
PMID:16823372
ORFeome cloning and global analysis of protein localization ... 		ACCEPT
Summary: ORFeome YFP screen places ppc1 in the cytosol.
Reason: S. pombe localisation; matches the PomBase CoA GO-CAM.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein
GO:0015937 coenzyme A biosynthetic process
IBA
GO_REF:0000033 		ACCEPT
Summary: PAINT IBA (PTN000265180) for CoA biosynthesis.
Reason: Core process.
Supporting Evidence:
PMID:23091701
We isolated a novel S. pombe temperature-sensitive strain ppc1-537 mutated in the catalytic region of phosphopantothenoylcysteine synthetase (designated Ppc1), which is essential for CoA synthesis.
PMID:23091701
The mutant becomes auxotrophic to pantothenate at permissive temperature, displaying greatly decreased levels of CoA, acetyl-CoA and histone acetylation.
GO:0015937 coenzyme A biosynthetic process
IEA
GO_REF:0000117 		ACCEPT
Summary: ARBA rule mapping to CoA biosynthesis. Correct.
Reason: Agrees with genetics.
Supporting Evidence:
PMID:23091701
We isolated a novel S. pombe temperature-sensitive strain ppc1-537 mutated in the catalytic region of phosphopantothenoylcysteine synthetase (designated Ppc1), which is essential for CoA synthesis.
GO:0015937 coenzyme A biosynthetic process
IMP
PMID:23091701
Impaired coenzyme A synthesis in fission yeast causes defect... 		ACCEPT
Summary: ppc1 ts mutants have greatly decreased CoA and acetyl-CoA levels.
Reason: Direct S. pombe genetic evidence; full text cached.
Supporting Evidence:
PMID:23091701
We isolated a novel S. pombe temperature-sensitive strain ppc1-537 mutated in the catalytic region of phosphopantothenoylcysteine synthetase (designated Ppc1), which is essential for CoA synthesis.
PMID:23091701
The mutant becomes auxotrophic to pantothenate at permissive temperature, displaying greatly decreased levels of CoA, acetyl-CoA and histone acetylation.

Core Functions

Phosphopantothenoylcysteine synthetase: condenses 4'-phosphopantothenate with L-cysteine to 4'-phosphopantothenoylcysteine, the second step of CoA biosynthesis, in the cytosol; essential for CoA and acetyl-CoA production.

Molecular Function:
phosphopantothenate--cysteine ligase activity
Directly Involved In:
coenzyme A biosynthetic process
Cellular Locations:
cytosol
Supporting Evidence:
  • PMID:23091701
    We isolated a novel S. pombe temperature-sensitive strain ppc1-537 mutated in the catalytic region of phosphopantothenoylcysteine synthetase (designated Ppc1), which is essential for CoA synthesis.
  • PMID:23091701
    The mutant becomes auxotrophic to pantothenate at permissive temperature, displaying greatly decreased levels of CoA, acetyl-CoA and histone acetylation.
  • PMID:23091701
    It is similar to human PPCS (amino acid identity 42%) and budding yeast Cab2 (identity 45%).
  • file:SCHPO/ppc1/ppc1-uniprot.txt
    SIMILARITY: Belongs to the PPC synthetase family.
  • PMID:23091701
    The GFP signals of both Ppc1 and Ptk1 were observed in the whole cell (figure 4e), whereas Acs1 was enriched in the nuclear chromatin.

References

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Suggested Questions for Experts

Q: Does S. pombe Ppc1 use CTP or ATP as the nucleotide (human PPCS is ATP-preferring, bacterial CoaB uses CTP)?

Q: Does S. pombe form a CoA-synthesizing protein complex comparable to the S. cerevisiae CoA-SPC (Cab2-Cab3-Cab4-Cab5-Sis2/Vhs3) with hal3 and cab4/cab5?

Suggested Experiments

Experiment: Assay recombinant Ppc1 (wild type, T48I, M209T) for phosphopantothenoylcysteine synthesis with ATP versus CTP.

📚 Additional Documentation

Notes

(ppc1-notes.md)

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