tam41 encodes the mitochondrial CDP-diacylglycerol synthase (phosphatidate cytidylyltransferase, EC 2.7.7.41) of Schizosaccharomyces pombe, the ortholog of S. cerevisiae Tam41/Mmp37 and human TAMM41. Unrelated in sequence to the ER CDS-family enzyme bbl1, Tam41 is a nucleotidyltransferase-fold protein with a winged-helix domain that binds CTP in an L-shaped pocket and uses a sequential mechanism to convert phosphatidic acid to CDP-DAG. A positively charged C-terminal amphipathic helix anchors it peripherally to the matrix face of the mitochondrial inner membrane, where its CDP-DAG feeds phosphatidylglycerophosphate synthase and cardiolipin synthase.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004605 phosphatidate cytidylyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PANTHER IBA from the Tam41 family node PTN000341245 (sources include S. cerevisiae Tam41 and tam41 itself, which carries its own IDA). Reason: Phylogenetic inference agrees with direct kinetic data for the S. pombe enzyme. Supporting Evidence: PMID:31178220 Here we show that Tam41 adopts sequential catalytic mechanism |
| GO:0004605 phosphatidate cytidylyltransferase activity | IDA PMID:31178220 Structures of the Mitochondrial CDP-DAG Synthase Tam41 Sugge... | ACCEPT | Summary: Jiao et al. (2019) assayed recombinant S. pombe Tam41, determined its sequential catalytic mechanism and kinetic parameters (Km for CTP and PA, recorded by UniProt), and solved apo and CTP-bound structures. Reason: Direct biochemical evidence for the core activity of this protein. Supporting Evidence: PMID:31178220 Here we show that Tam41 adopts sequential catalytic mechanism file:SCHPO/tam41/tam41-uniprot.txt KM=0.094 mM for phosphatidic acid |
| GO:0004605 phosphatidate cytidylyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from InterPro IPR015222 (Tam41 family), RHEA:16229 and EC 2.7.7.41. Reason: Correct mapping for the Tam41 family. Supporting Evidence: file:SCHPO/tam41/tam41-uniprot.txt Reaction=a 1,2-diacyl-sn-glycero-3-phosphate + CTP + H(+) = a CDP-1,2- |
| GO:0004605 phosphatidate cytidylyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Curator sequence-similarity transfer from S. cerevisiae Tam41 (P53230), which was shown to make CDP-DAG directly. Reason: Consistent with the direct S. pombe biochemistry. Supporting Evidence: PMID:23623749 Taken together, we conclude that Tam41 directly catalyzes the conversion of PA to CDP-DAG in the presence of CTP. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PANTHER IBA (PTN000341245) placing the Tam41 family in mitochondria (S. cerevisiae Tam41, rat and human TAMM41 sources). Reason: Correct though general; the specific site is the matrix face of the inner membrane. Supporting Evidence: file:SCHPO/tam41/tam41-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (SL-0168, mitochondrion inner membrane; peripheral, matrix side), itself by similarity to P53230. Reason: Correct; Tam41 acts at the inner membrane where its PA substrate resides. Supporting Evidence: file:SCHPO/tam41/tam41-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion inner membrane |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Curator transfer of inner-membrane location from S. cerevisiae Tam41. Reason: Correct; the S. pombe C-terminal amphipathic helix mediates membrane association, consistent with a peripheral inner-membrane enzyme. Supporting Evidence: PMID:23623749 Tam41 is a peripheral IM protein facing the matrix PMID:31178220 The C-terminal region of SpTam41 contains a positively charged amphipathic helix crucial for membrane association and participates in binding phospholipids. |
| GO:0005759 mitochondrial matrix | ISO GO_REF:0000024 | ACCEPT | Summary: PomBase ortholog transfer of mitochondrial matrix (is_active_in) from S. cerevisiae Tam41 (SGD:S000003278); this is the location used in the PomBase cardiolipin GO-CAM (67086be200000363). Reason: Tam41 is a matrix-facing peripheral inner-membrane protein, so the active site faces the matrix; consistent with the S. cerevisiae TAM41 review, which lists matrix and inner membrane. Supporting Evidence: PMID:23623749 Tam41 is a peripheral IM protein facing the matrix |
| GO:0007006 mitochondrial membrane organization | IC GO_REF:0000111 | KEEP AS NON CORE | Summary: PomBase curator inference from the cardiolipin biosynthetic process annotation (with GO:0032049) to mitochondrial membrane organization. Reason: Cardiolipin shapes the inner membrane, so tam41 contributes indirectly by supplying the CL precursor; the enzyme itself does not organize the membrane. Retained as a deliberate curator inference but not core. Supporting Evidence: PMID:31178220 In mitochondria, CDP-diacylglycerol (CDP-DAG) is a crucial precursor for cardiolipin biosynthesis. |
| GO:0016024 CDP-diacylglycerol biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PANTHER IBA (PTN000341245) to CDP-diacylglycerol biosynthetic process. Reason: Correct; this is the process tam41 catalyses. Supporting Evidence: PMID:31178220 Mitochondrial CDP-DAG is synthesized by the translocator assembly and maintenance protein 41 (Tam41) |
| GO:0016024 CDP-diacylglycerol biosynthetic process | IDA PMID:31178220 Structures of the Mitochondrial CDP-DAG Synthase Tam41 Sugge... | ACCEPT | Summary: Direct in vitro CDP-DAG synthesis by recombinant S. pombe Tam41. Reason: Core process, direct evidence. Supporting Evidence: PMID:31178220 Here we show that Tam41 adopts sequential catalytic mechanism PMID:31178220 Mitochondrial CDP-DAG is synthesized by the translocator assembly and maintenance protein 41 (Tam41) |
| GO:0016024 CDP-diacylglycerol biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway UPA00557 mapping (CDP-DAG biosynthesis, step 3/3). Reason: Correct pathway placement. Supporting Evidence: file:SCHPO/tam41/tam41-uniprot.txt Reaction=a 1,2-diacyl-sn-glycero-3-phosphate + CTP + H(+) = a CDP-1,2- |
| GO:0031314 extrinsic component of mitochondrial inner membrane | ISO GO_REF:0000024 | ACCEPT | Summary: PomBase ortholog transfer from S. cerevisiae Tam41 (peripheral inner-membrane protein facing the matrix). Reason: Accurately describes the topology of a matrix-side peripheral inner-membrane enzyme; supported in S. pombe by the membrane-binding amphipathic helix. Supporting Evidence: PMID:23623749 Tam41 is a peripheral IM protein facing the matrix PMID:31178220 The C-terminal region of SpTam41 contains a positively charged amphipathic helix crucial for membrane association and participates in binding phospholipids. |
| GO:0032049 cardiolipin biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PANTHER IBA (PTN000341245) to cardiolipin biosynthetic process, sourced from S. cerevisiae Tam41. Reason: Tam41 makes the mitochondrial CDP-DAG consumed by pgs1 and by cardiolipin synthase, so it performs a step of this pathway; consistent with the S. cerevisiae TAM41 review. Supporting Evidence: PMID:31178220 In mitochondria, CDP-diacylglycerol (CDP-DAG) is a crucial precursor for cardiolipin biosynthesis. |
| GO:0032049 cardiolipin biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro IPR015222 (Tam41 family) mapping to cardiolipin biosynthetic process. Reason: Correct for this family. Supporting Evidence: PMID:31178220 In mitochondria, CDP-diacylglycerol (CDP-DAG) is a crucial precursor for cardiolipin biosynthesis. |
| GO:0032049 cardiolipin biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: Curator transfer from S. cerevisiae Tam41 (P53230), required for cardiolipin synthesis. Reason: Correct; also the process of the PomBase cardiolipin GO-CAM. Supporting Evidence: PMID:31178220 In mitochondria, CDP-diacylglycerol (CDP-DAG) is a crucial precursor for cardiolipin biosynthesis. PMID:23623749 Taken together, we conclude that Tam41 directly catalyzes the conversion of PA to CDP-DAG in the presence of CTP. |
| GO:0070300 phosphatidic acid binding | IDA PMID:31178220 Structures of the Mitochondrial CDP-DAG Synthase Tam41 Sugge... | KEEP AS NON CORE | Summary: Phosphatidic acid binding from the Tam41 lipid-binding/docking experiments. PA is the substrate of the enzyme. Reason: Substrate binding is part of the catalytic activity already captured by GO:0004605; retained as non-core, deferring to the curator who read the full text. Supporting Evidence: PMID:31178220 Docking of phosphatidic acid/CDP-DAG in the structure suggests a lipid entry/exit pathway PMID:31178220 The C-terminal region of SpTam41 contains a positively charged amphipathic helix crucial for membrane association and participates in binding phospholipids. |
| GO:1901612 cardiolipin binding | IDA PMID:31178220 Structures of the Mitochondrial CDP-DAG Synthase Tam41 Sugge... | KEEP AS NON CORE | Summary: Cardiolipin binding from lipid-binding assays of the C-terminal amphipathic region, which the abstract says participates in binding phospholipids. Reason: Plausible membrane-anchoring property of the C-terminal helix rather than a distinct function; abstract-only, so the curator-read full text is deferred to. Supporting Evidence: PMID:31178220 The C-terminal region of SpTam41 contains a positively charged amphipathic helix crucial for membrane association and participates in binding phospholipids. |
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Download this section (compressed HTML)Q: Is the cardiolipin binding of the C-terminal amphipathic helix a product-feedback or targeting mechanism, and does it couple Tam41 to pgs1/crd1 at the inner membrane?
Experiment: Measure cardiolipin and PG levels and respiratory growth in S. pombe tam41 deletion and catalytic-site mutants to confirm that the mitochondrial CDP-DAG pool for cardiolipin depends on tam41 and not bbl1.
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