Mitochondrial phosphatidylglycerophosphate (PGP) phosphatase of fission yeast (EC 3.1.3.27), a small (209-residue) HAD-superfamily (subfamily IIIA) phosphatase of the GEP4 family. By orthology to S. cerevisiae Gep4, it hydrolyses PGP made by pgs1 to phosphatidylglycerol (PG) on the matrix side of the inner mitochondrial membrane, supplying PG for cardiolipin synthesis by crd1. The S. pombe protein localises to mitochondria in a genome-wide YFP-fusion screen; its enzymatic activity has not been measured directly in S. pombe.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MODIFY | Summary: IBA from the deep HAD PGP-phosphatase node PTN002711682 (donors include E. coli PgpA and plant/animal HAD phosphatases). For gep4 'cytoplasm' is formally a superset of the mitochondrion but misleading; the lineage-specific node already gives mitochondrion. Reason: gep4 acts in mitochondria (matrix side of the inner membrane); same treatment as in the S. cerevisiae GEP4 review. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN002711682 · PTN002711682 SUPPORTS SOURCE BUT NOT TARGET Deep HAD PGP-phosphatase node including bacterial PgpA; cytoplasm is right for the bacterial members but not for the mitochondrial fungal GEP4 clade. Proposed replacements: mitochondrial matrix Supporting Evidence: PMID:20485265 we identify a novel phosphatase in the mitochondrial matrix space, Gep4, and demonstrate that it dephosphorylates phosphatidylglycerolphosphate to generate phosphatidylglycerol, an essential step during CL biosynthesis |
| GO:0005739 mitochondrion | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: Genome-wide YFP-fusion localisation in S. pombe placed gep4 in mitochondria. Reason: S. pombe-specific localisation evidence consistent with the ortholog. 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 | ACCEPT | Summary: PAINT IBA from the fungal GEP4 node PTN001060726 (donor S. cerevisiae Gep4). Correct and consistent with the S. pombe HDA. Reason: Mitochondrial location is supported in both yeasts. Supporting Evidence: PMID:20485265 we identify a novel phosphatase in the mitochondrial matrix space, Gep4, and demonstrate that it dephosphorylates phosphatidylglycerolphosphate to generate phosphatidylglycerol, an essential step during CL biosynthesis |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping of 'Mitochondrion inner membrane; peripheral membrane protein; matrix side'. The UniProt record attributes this to the ORFeome study, which can resolve mitochondrion only, so the sub-mitochondrial detail is really by similarity to S. cerevisiae Gep4. Reason: Consistent with Gep4 being a peripheral protein on the matrix face of the inner membrane in S. cerevisiae; the sub-mitochondrial detail is inferred. Supporting Evidence: file:SCHPO/gep4/gep4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane PMID:20485265 we identify a novel phosphatase in the mitochondrial matrix space, Gep4, and demonstrate that it dephosphorylates phosphatidylglycerolphosphate to generate phosphatidylglycerol, an essential step during CL biosynthesis |
| GO:0005759 mitochondrial matrix | ISO GO_REF:0000024 | ACCEPT | Summary: PomBase ISO from S. cerevisiae Gep4 (SGD:S000001142), which was shown to be a matrix-space phosphatase. The PomBase GO-CAM also places gep4 activity in the matrix. Reason: Reasonable transfer from a close functional ortholog. Supporting Evidence: PMID:20485265 we identify a novel phosphatase in the mitochondrial matrix space, Gep4, and demonstrate that it dephosphorylates phosphatidylglycerolphosphate to generate phosphatidylglycerol, an essential step during CL biosynthesis |
| GO:0006655 phosphatidylglycerol biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway mapping (phosphatidylglycerol from CDP-diacylglycerol, step 2/2). PGP dephosphorylation produces PG directly. Reason: gep4 catalyses the PG-forming step. Supporting Evidence: file:SCHPO/gep4/gep4-uniprot.txt PATHWAY: Phospholipid metabolism; phosphatidylglycerol biosynthesis; |
| GO:0007006 mitochondrial membrane organization | IC GO_REF:0000111 | KEEP AS NON CORE | Summary: PomBase IC from the cardiolipin biosynthetic role. CL is needed for mitochondrial membrane architecture, but gep4's contribution is making a CL precursor. Reason: Indirect, downstream consequence of PG/CL synthesis; kept as non-core, consistent with the other CL-pathway enzymes. Supporting Evidence: PMID:20485265 we identify a novel phosphatase in the mitochondrial matrix space, Gep4, and demonstrate that it dephosphorylates phosphatidylglycerolphosphate to generate phosphatidylglycerol, an essential step during CL biosynthesis |
| GO:0008962 phosphatidylglycerophosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from fungal GEP4 node PTN001060726, seeded by S. cerevisiae Gep4 (IDA/IMP/IGI). A single well-characterised donor is adequate; S. pombe gep4 is a clear member of the GEP4 family (PF09419). Reason: Core activity by orthology to the characterised S. cerevisiae enzyme. Supporting Evidence: file:SCHPO/gep4/gep4-uniprot.txt FUNCTION: Phosphatidylglycerophosphatase involved in the biosynthesis file:SCHPO/gep4/gep4-uniprot.txt Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycero-3'-phosphate) PMID:20485265 we identify a novel phosphatase in the mitochondrial matrix space, Gep4, and demonstrate that it dephosphorylates phosphatidylglycerolphosphate to generate phosphatidylglycerol, an essential step during CL biosynthesis |
| GO:0008962 phosphatidylglycerophosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt combined IEA from InterPro IPR027706 (PGP phosphatase) and EC 3.1.3.27. Correct. Reason: Agrees with the phylogenetic inference. Supporting Evidence: file:SCHPO/gep4/gep4-uniprot.txt FUNCTION: Phosphatidylglycerophosphatase involved in the biosynthesis file:SCHPO/gep4/gep4-uniprot.txt Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycero-3'-phosphate) |
| GO:0032049 cardiolipin biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN001060726) for cardiolipin biosynthesis; S. cerevisiae gep4 mutants lack CL. Reason: gep4 catalyses an obligate step of CL synthesis (PG formation). Supporting Evidence: PMID:20485265 we identify a novel phosphatase in the mitochondrial matrix space, Gep4, and demonstrate that it dephosphorylates phosphatidylglycerolphosphate to generate phosphatidylglycerol, an essential step during CL biosynthesis |
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Download this section (compressed HTML)Q: Is S. pombe gep4 required for cardiolipin synthesis, or does a second PGP phosphatase (e.g. a PTPMT1-like enzyme) contribute in fission yeast?
Experiment: Lipidomics of a gep4 deletion in S. pombe (PGP accumulation, PG and CL loss), and PGP phosphatase assays with purified recombinant gep4.
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