cem1 (SPBC887.13c) encodes the fission yeast mitochondrial beta-ketoacyl-[acyl-carrier-protein] synthase (mtKAS, EC 2.3.1.41), a 426-residue freestanding FabF-like condensing enzyme of the thiolase-like superfamily. A predicted N-terminal mitochondrial presequence precedes a single ketosynthase (KS3) domain that retains the Cys-His-His catalytic triad (Cys170, His311, His351). By orthology with budding-yeast Cem1 and human OXSM it is expected to catalyse the decarboxylative Claisen condensation of malonyl-ACP with a growing acyl-ACP, the chain-extending step of the dissociated (type II) mitochondrial fatty acid synthase in the mitochondrial matrix. In other eukaryotes this pathway supplies octanoyl-ACP, the precursor of protein-bound lipoic acid, and longer acyl chains needed for respiratory competence. A genome-wide YFP-tagging screen places the S. pombe protein in mitochondria; its catalytic activity, chain-length preference and mutant phenotype have not been measured directly in fission yeast.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core catalytic activity, propagated from the PANTHER PTHR11712 node PTN000918584 that unites bacterial FabB/FabF/KasA/KasB, plant KAS and human mitochondrial OXSM. Reason: cem1 is classified in PANTHER subfamily PTHR11712:SF336 (3-oxoacyl-ACP synthase, mitochondrial) together with S. cerevisiae CEM1 and human/mouse OXSM, and it descends from the eukaryotic node PTN000918585 that carries the mitochondrial localisation of this lineage. The IBD at PTN000918584 is seeded by experimentally characterised condensing enzymes including human OXSM, which elongates C2-C14 acyl-ACP with malonyl-ACP and complements a cem1-null budding yeast (PMID:15668256). The fission yeast protein retains the full KS3 domain and the Cys-His-His catalytic triad (C170, H311, H351) that mtKAS enzymes use (PMID:17242430), so there is no sequence evidence for loss of activity. The node placement is therefore sound for this target. Supporting Evidence: file:SCHPO/cem1/cem1-uniprot.txt DR PANTHER; PTHR11712:SF336; 3-OXOACYL-[ACYL-CARRIER-PROTEIN] SYNTHASE, MITOCHONDRIAL; 1. file:SCHPO/cem1/cem1-uniprot.txt DR NCBIfam; TIGR03150; fabF; 1. file:SCHPO/cem1/cem1-uniprot.txt FT ACT_SITE 170 PMID:15668256 The enzyme can elongate acyl-chains containing 2-14 carbon atoms with malonyl moieties attached in thioester linkage to the human mitochondrial acyl carrier protein and is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase and exhibits lowered lipoic acid levels. PMID:17242430 KASes catalyze the C(2) fatty acid elongation reaction using either a Cys-His-His or Cys-His-Asn catalytic triad. |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Same core activity, mapped electronically from the EC 2.3.1.41 / Rhea reactions that UniProt attaches by similarity to human OXSM. Reason: Consistent with the IBA and ISS rows for the same term. The Rhea reactions describe malonyl-ACP-dependent elongation of C4-C14 acyl-ACP, the chemistry measured for human OXSM (PMID:15668256); the target retains the KS3 domain and catalytic triad. The exact chain-length range in S. pombe is not measured, but the term itself does not assert one. Supporting Evidence: file:SCHPO/cem1/cem1-uniprot.txt DR InterPro; IPR000794; Beta-ketoacyl_synthase. file:SCHPO/cem1/cem1-uniprot.txt FT ACT_SITE 311 PMID:15668256 The enzyme can elongate acyl-chains containing 2-14 carbon atoms with malonyl moieties attached in thioester linkage to the human mitochondrial acyl carrier protein |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Same core activity, transferred by curator judgement from human OXSM (Q9NWU1). Reason: Human OXSM sits in the same PANTHER subfamily (SF336) and the same eukaryotic mitochondrial clade (PTN000918585) as cem1, so the transfer is phylogenetically grounded, not a best-hit inference. OXSM activity and its ability to replace budding-yeast Cem1 are experimentally established (PMID:15668256). Supporting Evidence: PMID:15668256 is able to restore growth to the respiratory-deficient yeast mutant cem1 that lacks the endogenous mitochondrial beta-ketoacyl synthase file:SCHPO/cem1/cem1-uniprot.txt FT ACT_SITE 351 |
| GO:0005739 mitochondrion | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: Direct S. pombe localisation from the genome-wide YFP-tagged ORFeome screen. Reason: This is the only experimental observation on the fission yeast protein itself. PomBase curators recorded a mitochondrial pattern for the tagged ORF from this screen; the cached abstract does not list individual proteins, so the call is deferred to the curators. It agrees with the predicted N-terminal transit peptide (residues 1-18) and with mitochondrial targeting of the human 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 file:SCHPO/cem1/cem1-uniprot.txt FT TRANSIT 1..18 |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial localisation propagated from the eukaryotic node PTN000918585 (taxon Eukaryota), seeded by human OXSM and Trypanosoma brucei mtKAS. Reason: The PAINT curator placed mitochondrial localisation at the eukaryote-specific node of this lineage rather than at the deeper node shared with bacterial FabF. cem1 descends from it and carries its own predicted presequence and an independent HDA observation, so the inheritance is supported for this target. The only negated propagation in the family (NOT mitochondrion, PTN000196554) is restricted to a bacterial taxon and does not apply. Supporting Evidence: PMID:15668256 The full-length nuclear-encoded 459-residue protein includes an N-terminal sequence element of approximately 38 residues that functions as a mitochondrial targeting sequence. file:SCHPO/cem1/cem1-uniprot.txt FT TRANSIT 1..18 |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: Mitochondrial localisation mapped from the UniProt subcellular-location comment. Reason: Concordant with the HDA observation and the IBA propagation for the same term. The UniProt comment is itself by similarity, so this row adds no independent evidence, but the claim is correct. 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 file:SCHPO/cem1/cem1-uniprot.txt FT TRANSIT 1..18 |
| GO:0006633 fatty acid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Process in which the condensation step is performed; propagated from PTN000918584. Reason: The ketoacyl-ACP synthase directly performs the C-C bond-forming step of each elongation cycle, so it participates in (not merely supports) fatty acid biosynthesis. In mitochondria a single mtKAS carries out all elongation reactions (PMID:17242430). The budding-yeast cem1 null did not change bulk mitochondrial fatty acids (PMID:8412701), which is consistent with mtFAS making a specialised acyl-ACP pool rather than bulk lipid; the cytosolic Fas1/Fas2 complex makes bulk fatty acids. The term remains accurate for the mitochondrial pathway. PAINT curators did not propagate lipoate biosynthesis to this node; that omission is respected here. Supporting Evidence: PMID:17242430 By comparison, mtKAS carries out all elongation reactions in the mitochondria. PMID:15668256 The enzyme can elongate acyl-chains containing 2-14 carbon atoms with malonyl moieties attached in thioester linkage to the human mitochondrial acyl carrier protein |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Same process, mapped from the 3-oxoacyl-ACP synthase 2 InterPro family and UniPathway. Reason: Consistent with the IBA row for the same term; the IPR017568 (FabF-type) family match is appropriate classification evidence for a condensing enzyme of type II fatty acid synthesis. Supporting Evidence: file:SCHPO/cem1/cem1-uniprot.txt DR InterPro; IPR017568; 3-oxoacyl-ACP_synth-2. PMID:17242430 By comparison, mtKAS carries out all elongation reactions in the mitochondria. |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: Correct but very general parent of the supported activity, from the thiolase-like fold signature. Reason: 3-oxoacyl-[acyl-carrier-protein] synthase activity (GO:0004315) is an acyltransferase activity and is already carried by this gene with family, catalytic-residue and ortholog support, so the general term should be refined to it. Proposed replacements: 3-oxoacyl-[acyl-carrier-protein] synthase activity Supporting Evidence: file:SCHPO/cem1/cem1-uniprot.txt DR InterPro; IPR000794; Beta-ketoacyl_synthase. file:SCHPO/cem1/cem1-uniprot.txt FT ACT_SITE 170 |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IEA GO_REF:0000002 | MODIFY | Summary: Correct but general parent of the supported activity, from the FabF-type family signature. Reason: The same IPR017568 signature supports the specific 3-oxoacyl-[acyl-carrier-protein] synthase activity (GO:0004315), which the gene already carries; refine to that term. Proposed replacements: 3-oxoacyl-[acyl-carrier-protein] synthase activity Supporting Evidence: file:SCHPO/cem1/cem1-uniprot.txt DR InterPro; IPR017568; 3-oxoacyl-ACP_synth-2. |
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Download this section (compressed HTML)Q: Does S. pombe cem1 deletion abolish protein lipoylation (pyruvate and 2-oxoglutarate dehydrogenase E2 subunits) and respiratory growth, as the budding-yeast cem1 null does?
Q: Should the mtKAS step be linked to lipoate biosynthesis in GO for this lineage? PAINT curators propagated only fatty acid biosynthesis and the KAS activity to PTN000918584, so any octanoyl-ACP to lipoate link would need experimental support in a fungal or animal ortholog first.
Experiment: Complement a S. cerevisiae cem1-null strain with S. pombe cem1 (wild type and C170A) and assay respiratory growth and lipoylation, to test catalytic function and conservation.
Experiment: Assay recombinant mature Cem1 (residues 19-426) with S. pombe mitochondrial ACP-bound acyl substrates of increasing chain length to determine its chain-length preference.
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