Mitochondrial CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase (phosphatidylglycerophosphate synthase, PGPS; EC 2.7.8.5) of fission yeast. It transfers the phosphatidyl group of CDP-diacylglycerol to sn-glycerol 3-phosphate, forming phosphatidylglycerophosphate (PGP) and CMP; this is the committed step of the phosphatidylglycerol/cardiolipin branch of CDP-DAG-dependent phospholipid synthesis. The S. pombe enzyme was purified to homogeneity from mitochondrial membranes as a ~60 kDa polypeptide that depends on lipid activators (phosphatidic acid, CDP-DAG and especially cardiolipin), and its activity in cell extracts is regulated by growth phase and inositol. It belongs to the CDP-alcohol phosphatidyltransferase class-II (phospholipase D-like, HKD motif) family and is the ortholog of S. cerevisiae Pgs1. PGP is dephosphorylated to phosphatidylglycerol by gep4, and crd1 then forms cardiolipin.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping from IPR001736 (phospholipase D/transphosphatidylase HKD domain) gives the root MF 'catalytic activity'. True but uninformative: pgs1 has a specific, experimentally supported PGP synthase activity (GO:0008444). Reason: Replace the root term with the specific phosphatidyltransferase activity that is supported by purification of the S. pombe enzyme. Proposed replacements: CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity Supporting Evidence: file:SCHPO/pgs1/pgs1-uniprot.txt Reaction=a CDP-1,2-diacyl-sn-glycerol + sn-glycerol 3-phosphate = a PMID:9468529 In this work, we report the purification to homogeneity of PGPS from S. pombe. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN000287047 (with S. pombe pgs1 itself and S. cerevisiae Pgs1 among the descendants). Mitochondrial location is correct: the S. pombe enzyme was purified from mitochondrial membranes. Reason: Consistent with the S. pombe purification study and with the ortholog; mitochondrial inner membrane is the more precise location (core function). Supporting Evidence: PMID:9468529 is located in the mitochondrial inner membrane and catalyzes the committed step in the cardiolipin branch of phospholipid synthesis |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt ARBA/SubCell mapping of 'Mitochondrion' (by similarity) to GO:0005739. Correct but less precise than inner membrane. Reason: Correct location; the experimental purification places pgs1 in mitochondrial membranes. Supporting Evidence: file:SCHPO/pgs1/pgs1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250}. PMID:9468529 is located in the mitochondrial inner membrane and catalyzes the committed step in the cardiolipin branch of phospholipid synthesis |
| GO:0005759 mitochondrial matrix | IC PMID:9468529 Purification and characterization of phosphatidylglycerolpho... | MODIFY | Summary: PomBase IC (from GO:0032049) placing pgs1 activity in the mitochondrial matrix; the PomBase cardiolipin GO-CAM (67086be200000363) likewise puts pgs1 in the matrix. The cited paper states the enzyme is in the mitochondrial inner membrane and it had to be solubilised from mitochondrial membranes with Triton X-100, i.e. it is membrane-associated, not a soluble matrix protein. Reason: The cited S. pombe evidence supports an inner-membrane location (the catalytic site may face the matrix, but the protein is membrane-bound); this matches the S. cerevisiae Pgs1 core location. Proposed replacements: mitochondrial inner membrane Supporting Evidence: PMID:9468529 is located in the mitochondrial inner membrane and catalyzes the committed step in the cardiolipin branch of phospholipid synthesis PMID:9468529 The enzyme was solubilized from the mitochondrial membrane of S. pombe with Triton X-100. |
| GO:0006655 phosphatidylglycerol biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway mapping (phosphatidylglycerol from CDP-diacylglycerol, step 1/2). PGP is the immediate precursor of PG, so pgs1 catalyses a step of PG synthesis. Reason: pgs1 directly catalyses the first step of PG synthesis. Supporting Evidence: file:SCHPO/pgs1/pgs1-uniprot.txt PATHWAY: Phospholipid metabolism; phosphatidylglycerol biosynthesis; |
| GO:0007006 mitochondrial membrane organization | IC PMID:9468529 Purification and characterization of phosphatidylglycerolpho... | KEEP AS NON CORE | Summary: PomBase IC inferring mitochondrial membrane organization from the cardiolipin biosynthetic role. CL is required for mitochondrial membrane architecture, but pgs1's contribution is synthesis of a lipid precursor, i.e. an indirect, downstream role. Reason: Defensible as a consequence of making CL (mitochondrial membrane biogenesis) but not the core activity; kept as non-core for consistency with the treatment of the CL pathway enzymes (S. cerevisiae CRD1 review). Supporting Evidence: PMID:9468529 is located in the mitochondrial inner membrane and catalyzes the committed step in the cardiolipin branch of phospholipid synthesis |
| GO:0008444 CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity | EXP PMID:1324908 Regulation of CDP-diacylglycerol synthesis and utilization b... | ACCEPT | Summary: PGP synthase activity was assayed in S. pombe cell extracts and shown to be regulated by growth phase and inositol. The activity measured is that of the gene product of pgs1 (the only PGPS in S. pombe). Reason: Direct enzyme assays of S. pombe PGP synthase; curator-assigned EXP from a paper whose full text is not cached. Supporting Evidence: PMID:1324908 membrane-associated phospholipid biosynthetic enzymes CDP-DG synthase, phosphatidylglycerolphosphate (PGP) synthase, phosphatidylinositol (PI) synthase, and phosphatidylserine (PS) synthase in cell extracts of the fission yeast Schizosaccharomyces pombe |
| GO:0008444 CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN000287047; S. pombe pgs1 appears among its own donors, which reflects its own experimental grounding (IDA/EXP) rather than circularity. Reason: Core activity, supported by the S. pombe purification and by the S. cerevisiae ortholog. Supporting Evidence: file:SCHPO/pgs1/pgs1-uniprot.txt Reaction=a CDP-1,2-diacyl-sn-glycerol + sn-glycerol 3-phosphate = a PMID:9468529 In this work, we report the purification to homogeneity of PGPS from S. pombe. |
| GO:0008444 CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity | IDA PMID:9468529 Purification and characterization of phosphatidylglycerolpho... | ACCEPT | Summary: Purification to homogeneity of PGPS from S. pombe mitochondria; the purified ~60 kDa protein has CDP-DAG:sn-glycerol-3-phosphate phosphatidyltransferase activity that is stimulated by phosphatidic acid, CDP-DAG and cardiolipin. Reason: Direct biochemical evidence for the core MF in S. pombe. Supporting Evidence: PMID:9468529 In this work, we report the purification to homogeneity of PGPS from S. pombe. PMID:9468529 The enzyme showed a strong dependence on lipid cofactors for activity in vitro. |
| GO:0008444 CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt combined IEA (ARBA, InterPro IPR016270 PGS1, RHEA:12593, EC 2.7.8.5). Correct. Reason: Agrees with experimental and phylogenetic evidence. Supporting Evidence: file:SCHPO/pgs1/pgs1-uniprot.txt Reaction=a CDP-1,2-diacyl-sn-glycerol + sn-glycerol 3-phosphate = a |
| GO:0016024 CDP-diacylglycerol biosynthetic process | EXP PMID:1324908 Regulation of CDP-diacylglycerol synthesis and utilization b... | MODIFY | Summary: PomBase EXP annotation of pgs1 to 'CDP-diacylglycerol biosynthetic process' from the Gaynor & Greenberg study of CDP-DG synthase, PGP synthase, PI synthase and PS synthase regulation. pgs1 encodes PGP synthase, which CONSUMES CDP-diacylglycerol (the phosphatidyl donor) and produces PGP; CDP-DAG formation from PA and CTP is catalysed by CDP-DG synthase (cds1, and tam41 in mitochondria). The paper measured CDP-DG synthase as a separate enzyme activity, so the term most likely reflects that activity being attached to the wrong gene product or a mis-chosen term. Reason: The experimental row is kept but re-pointed: CDP-DAG is the substrate of pgs1, not its product, so the process it participates in is phosphatidylglycerol biosynthesis. MODIFY rather than REMOVE matches the treatment of the same-paper row on pps1 (PS synthase). Proposed replacements: phosphatidylglycerol biosynthetic process Supporting Evidence: file:SCHPO/pgs1/pgs1-uniprot.txt Reaction=a CDP-1,2-diacyl-sn-glycerol + sn-glycerol 3-phosphate = a PMID:1324908 membrane-associated phospholipid biosynthetic enzymes CDP-DG synthase, phosphatidylglycerolphosphate (PGP) synthase |
| GO:0031966 mitochondrial membrane | IDA PMID:9468529 Purification and characterization of phosphatidylglycerolpho... | ACCEPT | Summary: PGPS was solubilised from S. pombe mitochondrial membranes and the paper states it resides in the inner membrane. Reason: Direct experimental evidence; mitochondrial inner membrane is the more specific location used in core_functions. Supporting Evidence: PMID:9468529 The enzyme was solubilized from the mitochondrial membrane of S. pombe with Triton X-100. |
| GO:0032049 cardiolipin biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000287047) for cardiolipin biosynthesis. PGP synthase catalyses the committed step of the CL branch. Reason: Core process. Supporting Evidence: PMID:9468529 is located in the mitochondrial inner membrane and catalyzes the committed step in the cardiolipin branch of phospholipid synthesis |
| GO:0032049 cardiolipin biosynthetic process | IDA PMID:9468529 Purification and characterization of phosphatidylglycerolpho... | ACCEPT | Summary: Purified S. pombe PGPS; the paper frames the activity as the committed step of cardiolipin synthesis. Reason: pgs1 performs the first step of CL synthesis; supported by direct biochemistry. Supporting Evidence: PMID:9468529 is located in the mitochondrial inner membrane and catalyzes the committed step in the cardiolipin branch of phospholipid synthesis |
| GO:0032049 cardiolipin biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt combined IEA (ARBA, InterPro IPR016270). Correct. Reason: Agrees with experimental evidence. Supporting Evidence: PMID:9468529 is located in the mitochondrial inner membrane and catalyzes the committed step in the cardiolipin branch of phospholipid synthesis |
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Download this section (compressed HTML)Q: Does the catalytic site of S. pombe pgs1 face the matrix (as the PomBase GO-CAM implies by placing it in the matrix) while the protein is anchored in the inner membrane?
Experiment: Protease-protection and carbonate-extraction assays on isolated S. pombe mitochondria expressing tagged pgs1 to define its membrane topology.
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