Probable 2-dehydropantoate 2-reductase (ketopantoate reductase, PanE-like; EC 1.1.1.169) of fission yeast, encoded by SPBPB2B2.09c. By homology it reduces 2-dehydropantoate to (R)-pantoate using NADPH, the second step of pantoate synthesis, which with beta-alanine is condensed to pantothenate by pan6. The protein is cytosolic and nuclear in a genome-wide YFP-fusion screen. Activity has not been measured in S. pombe, and in S. cerevisiae loss of the ortholog PAN5 still allows prototrophic growth, implying redundancy with other reductases.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: Genome-wide YFP-fusion screen detected pan5 in the nucleus as well as the cytosol. A small soluble enzyme often gives nuclear+cytosolic signal; no nuclear role is known. Reason: High-throughput observation without a functional nuclear role. 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:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN002464833) for cytoplasm; consistent with the S. pombe HDA cytosol observation. Reason: Supported by S. pombe localisation data. 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:0005739 mitochondrion | IBA GO_REF:0000033 | REMOVE | Summary: IBA for mitochondrion from the fungal node PTN001093729, whose only donor is SGD:S000002605. That SGD id is not S. cerevisiae PAN5 (SGD:S000001105); the S. cerevisiae PAN5 review identifies it as CBS2, a divergent mitochondrial member of this family (a cytochrome b translational activator). pan5 has no predicted transit peptide and was seen in cytosol and nucleus in S. pombe. The PomBase pantothenate GO-CAM (67b1629100001098) nevertheless places pan5 activity in the mitochondrion on the basis of this IBA. Reason: Location propagated from a functionally divergent paralog; S. pombe localisation data (cytosol/nucleus) contradict it. Same conclusion as the S. cerevisiae PAN5 review. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN001093729 · PTN001093729 SUPPORTS SOURCE BUT NOT TARGET Fungal IBD node in PTHR43765 for mitochondrion with a single SGD donor that is not PAN5. SGD:S000002605 · CBS2 (per S. cerevisiae PAN5 review) SUPPORTS SOURCE BUT NOT TARGET Mitochondrial location reflects the divergent function of the donor, not the ketopantoate reductase. 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:0005829 cytosol | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: Genome-wide YFP-fusion screen placed pan5 in the cytosol; consistent with S. cerevisiae Pan5 (cytoplasmic). Reason: S. pombe-specific localisation evidence; the main site of activity. 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:0008677 2-dehydropantoate 2-reductase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from the canonical PanE node PTN002464833 (donors E. coli PanE and another characterised bacterial KPR). Reason: Core activity by phylogenetic inference; the active-site and NADP-binding residues are annotated in UniProt. Supporting Evidence: file:SCHPO/pan5/pan5-uniprot.txt FUNCTION: Catalyzes the NADPH-dependent reduction of ketopantoate into file:SCHPO/pan5/pan5-uniprot.txt Reaction=(R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH + H(+); file:SCHPO/pan5/pan5-uniprot.txt SIMILARITY: Belongs to the ketopantoate reductase family. |
| GO:0008677 2-dehydropantoate 2-reductase activity | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt combined IEA (InterPro IPR003710, RHEA:16233, EC 1.1.1.169). Correct. Reason: Agrees with phylogenetic inference. Supporting Evidence: file:SCHPO/pan5/pan5-uniprot.txt Reaction=(R)-pantoate + NADP(+) = 2-dehydropantoate + NADPH + H(+); file:SCHPO/pan5/pan5-uniprot.txt SIMILARITY: Belongs to the ketopantoate reductase family. |
| GO:0015940 pantothenate biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt combined IEA (InterPro IPR003710, UniPathway UPA00028). Correct. Reason: Ketopantoate reduction is a step of pantoate/pantothenate synthesis. Supporting Evidence: file:SCHPO/pan5/pan5-uniprot.txt PATHWAY: Cofactor biosynthesis; (R)-pantothenate biosynthesis; (R)- |
| GO:0015940 pantothenate biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: PomBase ISS from S. cerevisiae Pan5 (P38787). Correct by orthology, although in S. cerevisiae PAN5 is not essential for pantothenate prototrophy (redundancy). Reason: Consistent with the predicted activity. Supporting Evidence: file:SCHPO/pan5/pan5-uniprot.txt FUNCTION: Catalyzes the NADPH-dependent reduction of ketopantoate into PMID:19266201 loss of PAN5 (related to panE from E. coli) still allows prototrophic growth |
| GO:0050661 NADP binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT IBA (PTN002464833) for NADP binding, from E. coli PanE. pan5 has the conserved N-terminal Rossmann NADP-binding motif annotated in UniProt. Reason: Cofactor binding inherent to the reductase activity; not a separate function. Supporting Evidence: file:SCHPO/pan5/pan5-uniprot.txt FUNCTION: Catalyzes the NADPH-dependent reduction of ketopantoate into |
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Download this section (compressed HTML)Q: Is S. pombe pan5 the sole ketopantoate reductase, or (as suggested for S. cerevisiae PAN5) do other reductases supply pantoate?
Experiment: Assay NADPH-dependent 2-dehydropantoate reduction by recombinant pan5 and test pantothenate prototrophy of a pan5 deletion in a liz1 background.
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