erg8

UniProt ID: Q9UT88
Organism: Schizosaccharomyces pombe 972h-
Review Status: COMPLETE
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Gene Description

erg8 (SPAC343.01c) encodes the fission-yeast GHMP-family phosphomevalonate kinase. The enzyme phosphorylates (R)-mevalonate 5-phosphate with ATP to form (R)-mevalonate 5-diphosphate, the second of three mevalonate-pathway reactions that produce isopentenyl diphosphate and feed fungal sterol biosynthesis. The protein is cytosolic by PomBase curation from the genome-wide S. pombe ORFeome localization screen, and the same screen also reported nuclear and mitochondrial signal for the tagged protein.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004631 phosphomevalonate kinase activity
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT infers phosphomevalonate kinase activity from PTN001274235, the GHMP-type phosphomevalonate kinase node seeded by Arabidopsis PMK and S. cerevisiae ERG8. S. pombe erg8 is a PTHR31814:SF2 family member and UniProt carries the expected Rhea reaction, so this core MF propagates correctly.
Supporting Evidence:
file:SCHPO/erg8/erg8-uniprot.txt
Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + ADP; Xref=Rhea:RHEA:16341
file:SCHPO/erg8/erg8-uniprot.txt
PANTHER; PTHR31814:SF2; PHOSPHOMEVALONATE KINASE; 1.
GO:0004631 phosphomevalonate kinase activity
IEA
GO_REF:0000120
ACCEPT
Summary: Combined automated EC/Rhea/InterPro mapping to the same PMK reaction. Correct.
Supporting Evidence:
file:SCHPO/erg8/erg8-uniprot.txt
Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + ADP; Xref=Rhea:RHEA:16341
file:SCHPO/erg8/erg8-uniprot.txt
InterPro; IPR016005; Erg8.
GO:0004631 phosphomevalonate kinase activity
ISS
GO_REF:0000024
ACCEPT
Summary: Curator transfer from S. cerevisiae ERG8 to its S. pombe ortholog. The transfer is consistent with the PAINT placement and with the UniProt catalytic reaction on Q9UT88.
Supporting Evidence:
file:SCHPO/erg8/erg8-uniprot.txt
Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + ADP; Xref=Rhea:RHEA:16341
GO:0005634 nucleus
EXP
PMID:16823372
ORFeome cloning and global analysis of protein localization ...
KEEP AS NON CORE
Summary: The ORFeome YFP screen reported nuclear erg8 signal. No nuclear phosphomevalonate-kinase role is known, but this EXP localization should be retained as a non-core high-throughput observation.
Reason: High-throughput localization with no known nuclear function.
Supporting Evidence:
PMID:16823372
Next, 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
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: UniProt SubCell mapping of the same nuclear localization. Keep as non-core.
Reason: High-throughput localization with no known nuclear function.
Supporting Evidence:
file:SCHPO/erg8/erg8-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Mitochondrion {ECO:0000269|PubMed:16823372}. Nucleus {ECO:0000269|PubMed:16823372}.
GO:0005737 cytoplasm
EXP
PMID:16823372
ORFeome cloning and global analysis of protein localization ...
ACCEPT
Summary: Cytoplasmic localization from the ORFeome YFP screen. Correct for a soluble PMK.
Supporting Evidence:
PMID:16823372
Next, 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:0005737 cytoplasm
IEA
GO_REF:0000120
ACCEPT
Summary: UniProt SubCell mapping of the experimentally reported cytoplasmic localization. Correct.
Supporting Evidence:
file:SCHPO/erg8/erg8-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Mitochondrion {ECO:0000269|PubMed:16823372}. Nucleus {ECO:0000269|PubMed:16823372}.
GO:0005739 mitochondrion
EXP
PMID:16823372
ORFeome cloning and global analysis of protein localization ...
UNDECIDED
Summary: The ORFeome YFP screen also recorded mitochondrial signal. Fungal Erg8 is expected to catalyze a cytosolic mevalonate-pathway step, and the cached Matsuyama et al. record is abstract-only, so the screen call cannot be adjudicated further here.
Reason: The mitochondrial call comes from the same abstract-only high-throughput localization screen as the accepted cytosol and cytoplasm calls, but mitochondrial localization conflicts with the conserved cytosolic mevalonate-pathway role and cannot be resolved from the cached evidence.
Supporting Evidence:
PMID:16823372
Next, 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:0005739 mitochondrion
IEA
GO_REF:0000044
UNDECIDED
Summary: UniProt SubCell mapping of the mitochondrial localization from the ORFeome screen. The underlying high-throughput observation cannot be checked from the cached abstract.
Reason: The mitochondrial UniProtKB-SubCell mapping traces to the same abstract-only high-throughput screen as the accepted cytosol and cytoplasm calls, but mitochondrial localization conflicts with the conserved cytosolic mevalonate-pathway role and cannot be resolved from the cached evidence.
Supporting Evidence:
file:SCHPO/erg8/erg8-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Mitochondrion {ECO:0000269|PubMed:16823372}. Nucleus {ECO:0000269|PubMed:16823372}.
GO:0005777 peroxisome
IBA
GO_REF:0000033
REMOVE
Summary: The peroxisome IBA comes from PTN000781523, a plant PMK node seeded by Arabidopsis AT1G31910. PTHR31814 fungal members inherit the PMK activity from PTN001274235, but the peroxisome placement is a plant-lineage localization that should not propagate to S. pombe erg8.
Reason: The PANTHER family review marks PTN000781523/GO:0005777 as NEEDS_PRUNING: fungal Erg8 catalyzes a cytosolic mevalonate-pathway step, while the peroxisomal placement is supported for the plant PMK seed and not for the fungal ERG8 clade.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: COMPARTMENT OR COMPLEX MISMATCH LINEAGE OR TAXON MISMATCH
Sources checked:
PANTHER:PTN000781523 Β· PTN000781523 SUPPORTS SOURCE BUT NOT TARGET
Plant peroxisomal PMK is not the fungal cytosolic ERG8 localization state.
Supporting Evidence:
file:SCHPO/erg8/erg8-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Mitochondrion {ECO:0000269|PubMed:16823372}. Nucleus {ECO:0000269|PubMed:16823372}.
file:SCHPO/erg8/erg8-uniprot.txt
PANTHER; PTHR31814:SF2; PHOSPHOMEVALONATE KINASE; 1.
GO:0005829 cytosol
HDA
PMID:16823372
ORFeome cloning and global analysis of protein localization ...
ACCEPT
Summary: PomBase curates cytosolic localization from the ORFeome YFP screen; this agrees with the expected soluble mevalonate-pathway PMK activity.
Supporting Evidence:
PMID:16823372
Next, 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:0006696 ergosterol biosynthetic process
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT infers the fungal ergosterol-biosynthesis process from PTN001274236, a fungal node seeded by S. cerevisiae ERG8. erg8 provides the PMK step in the upstream mevalonate pathway that supplies isopentenyl diphosphate for sterol biosynthesis.
Supporting Evidence:
file:SCHPO/erg8/erg8-uniprot.txt
Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: step 2/3.
file:SCHPO/erg8/erg8-uniprot.txt
Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + ADP; Xref=Rhea:RHEA:16341
GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT infers the IPP biosynthesis term from the same PTN001274235 node that carries phosphomevalonate kinase activity. erg8 directly catalyzes step 2/3 from mevalonate to IPP.
Supporting Evidence:
file:SCHPO/erg8/erg8-uniprot.txt
Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: step 2/3.
file:SCHPO/erg8/erg8-uniprot.txt
Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + ADP; Xref=Rhea:RHEA:16341
GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway
IEA
GO_REF:0000041
ACCEPT
Summary: UniPathway mapping to IPP biosynthesis via the mevalonate pathway. Correct core BP.
Supporting Evidence:
file:SCHPO/erg8/erg8-uniprot.txt
Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: step 2/3.

Core Functions

Phosphorylates (R)-mevalonate 5-phosphate with ATP to form (R)-mevalonate 5-diphosphate in the cytosolic mevalonate pathway to isopentenyl diphosphate, upstream of ergosterol biosynthesis.

Supporting Evidence:
  • file:SCHPO/erg8/erg8-uniprot.txt
    Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + ADP; Xref=Rhea:RHEA:16341
  • file:SCHPO/erg8/erg8-uniprot.txt
    Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: step 2/3.
  • PMID:16823372
    Next, 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.

References

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Notes

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