Fission yeast cardiolipin synthase (CMP-forming; EC 2.7.8.41), encoded by SPAC22A12.08c as the C-terminal part of a tandem fusion protein whose N-terminal part is a HAD-like mitochondrial hydrolase of unknown function. The CL synthase transfers the phosphatidyl group of CDP-diacylglycerol to phosphatidylglycerol to form cardiolipin in the mitochondrial inner membrane, the last step of the CDP-DAG route to cardiolipin. Unlike S. cerevisiae crd1 mutants, the S. pombe gene is essential; S. pombe and S. cerevisiae CL synthases complement each other. Functional CL synthase is produced only from a minor transcript that retains intron IV (isoform 1), whereas the major spliced transcript encodes only the hydrolase part; the precursor is imported into mitochondria and proteolytically processed.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: Genome-wide YFP-fusion localisation placed the SPAC22A12.08c product in mitochondria. Reason: Consistent with the dedicated study. 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 (PTN000370358) for mitochondrion; S. pombe crd1 is among the donors because it has its own IDA. Reason: Correct; inner membrane is the precise location. Supporting Evidence: file:SCHPO/crd1/crd1-uniprot.txt Mitochondrion inner membrane {ECO:0000305|PubMed:29958934}; Multi-pass |
| GO:0005739 mitochondrion | IDA PMID:29958934 Schizosaccharomyces pombe cardiolipin synthase is part of a ... | ACCEPT | Summary: The dedicated S. pombe study localised the fusion protein/its products to mitochondria. Reason: Direct S. pombe evidence (abstract describes a mitochondrial fusion protein). Supporting Evidence: PMID:29958934 It is encoded by the ORF SPAC22A12.08c as a C terminal part of a tandem fusion protein together with a mitochondrial hydrolase of unknown function. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping of 'Mitochondrion'. Correct. Reason: Consistent with experimental data. Supporting Evidence: file:SCHPO/crd1/crd1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16823372}. |
| GO:0005743 mitochondrial inner membrane | IC GO_REF:0000111 | ACCEPT | Summary: PomBase IC inferring inner membrane from the CMP-forming CL synthase activity (the C-terminal CLS domain has two predicted TM helices). Reason: CL synthase is an integral inner-membrane enzyme in S. cerevisiae; consistent with the predicted TM helices of the S. pombe CLS domain. Supporting Evidence: file:SCHPO/crd1/crd1-uniprot.txt Mitochondrion inner membrane {ECO:0000305|PubMed:29958934}; Multi-pass |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping of 'Mitochondrion inner membrane' for the CL synthase chain. Reason: Correct location of the CLS chain. Supporting Evidence: file:SCHPO/crd1/crd1-uniprot.txt Mitochondrion inner membrane {ECO:0000305|PubMed:29958934}; Multi-pass |
| GO:0006644 phospholipid metabolic process | IEA GO_REF:0000117 | TOO GENERAL | Summary: ARBA rule mapping to the broad term 'phospholipid metabolic process'. True but very general. Reason: Correct, if general; the specific process (cardiolipin biosynthesis) is also annotated. Supporting Evidence: file:SCHPO/crd1/crd1-uniprot.txt of cardiolipin (CL) (diphosphatidylglycerol) by specifically |
| GO:0007006 mitochondrial membrane organization | ISO GO_REF:0000024 | KEEP AS NON CORE | Summary: PomBase ISO from S. cerevisiae CRD1 (IMP for mitochondrial membrane organization). CL loss perturbs mitochondrial membranes, so crd1 contributes indirectly through CL production. Reason: Downstream consequence of CL synthesis; same treatment as in the S. cerevisiae CRD1 review. Supporting Evidence: PMID:29958934 Expression of S. pombe CL synthase is able to complement deletion of the CRD1 gene of Saccharomyces cerevisiae |
| GO:0008610 lipid biosynthetic process | IEA GO_REF:0000117 | MODIFY | Summary: ARBA rule mapping to 'lipid biosynthetic process'. Correct but overly general. Reason: Use the specific process supported by S. pombe genetics. Proposed replacements: cardiolipin biosynthetic process Supporting Evidence: file:SCHPO/crd1/crd1-uniprot.txt of cardiolipin (CL) (diphosphatidylglycerol) by specifically |
| GO:0008654 phospholipid biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from IPR000462 (CDP-alcohol phosphatidyltransferase). Correct parent of cardiolipin biosynthesis. Reason: Correct, general. Supporting Evidence: file:SCHPO/crd1/crd1-uniprot.txt of cardiolipin (CL) (diphosphatidylglycerol) by specifically |
| GO:0008808 cardiolipin synthase activity | ISO GO_REF:0000024 | MODIFY | Summary: PomBase ISO from S. cerevisiae CRD1 to GO:0008808 'cardiolipin synthase activity'. In current GO this term is defined as PG + PG -> cardiolipin + glycerol (the bacterial phospholipase D-type reaction, RHEA:31451), which is NOT the reaction of the eukaryotic enzyme; crd1 uses CDP-DAG + PG and releases CMP (GO:0043337). Reason: Wrong reaction variant; the eukaryotic CDP-alcohol phosphatidyltransferase-type CL synthase is captured by GO:0043337. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: SGD:S000002301 · CRD1 SUPPORTS TRANSFER S. cerevisiae CRD1 is a CMP-forming CL synthase; the transferred term GO:0008808 is now defined as the PG+PG (PLD-type) reaction, so the term, not the ortholog, is wrong. Proposed replacements: cardiolipin synthase (CMP-forming) activity Supporting Evidence: file:SCHPO/crd1/crd1-uniprot.txt of cardiolipin (CL) (diphosphatidylglycerol) by specifically file:SCHPO/crd1/crd1-uniprot.txt Reaction=a CDP-1,2-diacyl-sn-glycerol + a 1,2-diacyl-sn-glycero-3- |
| GO:0016020 membrane | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from IPR000462 to 'membrane'. True (inner membrane) but uninformative. Reason: Correct but general; the specific location is mitochondrial inner membrane. Supporting Evidence: file:SCHPO/crd1/crd1-uniprot.txt Mitochondrion inner membrane {ECO:0000305|PubMed:29958934}; Multi-pass |
| GO:0016780 phosphotransferase activity, for other substituted phosphate groups | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/InterPro mapping to the parent class 'phosphotransferase activity, for other substituted phosphate groups'. Correct parent of the CMP-forming CL synthase activity. Reason: Correct, general; GO:0043337 is the specific activity. Supporting Evidence: file:SCHPO/crd1/crd1-uniprot.txt of cardiolipin (CL) (diphosphatidylglycerol) by specifically |
| GO:0016787 hydrolase activity | ISM GO_REF:0000050 | KEEP AS NON CORE | Summary: PomBase ISM from IPR006357 (HAD-superfamily hydrolase subfamily IIA) for the N-terminal mitochondrial hydrolase part of the fusion protein. The domain is real, but its substrate is unknown and its activity is dispensable for viability; it is distinct from the CL synthase. Reason: Plausible activity of the N-terminal HAD domain (a separate mature chain), but uncharacterised and not part of the CL synthase function. Supporting Evidence: file:SCHPO/crd1/crd1-uniprot.txt SIMILARITY: In the N-terminal section; belongs to the HAD-like file:SCHPO/crd1/crd1-uniprot.txt FUNCTION: [Mitochondrial hydrolase]: Activity is dispensable for PMID:29958934 It is encoded by the ORF SPAC22A12.08c as a C terminal part of a tandem fusion protein together with a mitochondrial hydrolase of unknown function. |
| GO:0032049 cardiolipin biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000370438) for cardiolipin biosynthesis; correct. Reason: Core process. Supporting Evidence: PMID:29958934 Expression of S. pombe CL synthase is able to complement deletion of the CRD1 gene of Saccharomyces cerevisiae |
| GO:0032049 cardiolipin biosynthetic process | IMP PMID:29958934 Schizosaccharomyces pombe cardiolipin synthase is part of a ... | ACCEPT | Summary: The S. pombe CL synthase is essential; genetic analysis and cross-species complementation link SPAC22A12.08c to cardiolipin synthesis. Reason: Direct S. pombe genetic evidence. Supporting Evidence: PMID:29958934 Here we show that CL synthase is an essential protein in S. pombe. PMID:29958934 Expression of S. pombe CL synthase is able to complement deletion of the CRD1 gene of Saccharomyces cerevisiae |
| GO:0043337 cardiolipin synthase (CMP-forming) activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000370438), with S. pombe crd1 among descendants that carry experimental evidence. Correct. Reason: Core activity. Supporting Evidence: file:SCHPO/crd1/crd1-uniprot.txt of cardiolipin (CL) (diphosphatidylglycerol) by specifically PMID:29958934 It is encoded by the ORF SPAC22A12.08c as a C terminal part of a tandem fusion protein together with a mitochondrial hydrolase of unknown function. PMID:29958934 Expression of S. pombe CL synthase is able to complement deletion of the CRD1 gene of Saccharomyces cerevisiae |
| GO:0043337 cardiolipin synthase (CMP-forming) activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC2GO mapping from EC 2.7.8.41. Correct. Reason: Agrees with experimental evidence. Supporting Evidence: file:SCHPO/crd1/crd1-uniprot.txt of cardiolipin (CL) (diphosphatidylglycerol) by specifically |
| GO:0043337 cardiolipin synthase (CMP-forming) activity | IMP PMID:29958934 Schizosaccharomyces pombe cardiolipin synthase is part of a ... | ACCEPT | Summary: Reciprocal complementation between S. pombe SPAC22A12.08c and S. cerevisiae CRD1, and identification of the CL synthase-producing transcript, support CMP-forming CL synthase activity. Reason: Direct S. pombe evidence; curator read full text (abstract-only in cache). Supporting Evidence: PMID:29958934 Expression of S. pombe CL synthase is able to complement deletion of the CRD1 gene of Saccharomyces cerevisiae PMID:29958934 Functional CL synthase, however, is produced only from the minor SPAC22A12.08c derived mRNA that has intron IV retained. |
| GO:0055091 phospholipid homeostasis | IMP PMID:29958934 Schizosaccharomyces pombe cardiolipin synthase is part of a ... | KEEP AS NON CORE | Summary: PomBase IMP for phospholipid homeostasis, presumably reflecting altered phospholipid composition (loss of CL) when CL synthase expression is perturbed. This is a consequence of losing the biosynthetic activity. Reason: Phenotypic consequence of losing CL synthesis rather than a distinct homeostatic activity; curator-assigned from full text not in the cache. Supporting Evidence: PMID:29958934 Here we show that CL synthase is an essential protein in S. pombe. |
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Download this section (compressed HTML)Q: What is the substrate of the N-terminal HAD-like mitochondrial hydrolase domain fused to S. pombe CL synthase, and is the fusion functionally meaningful for cardiolipin synthesis or remodelling?
Q: Why is CL synthase essential in S. pombe but dispensable in S. cerevisiae?
Experiment: Purify the processed N-terminal hydrolase chain and screen phosphatase/hydrolase activity on lipid and small-molecule phosphate substrates (e.g. PGP, nucleotide phosphates).
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