TAM41 (MMP37, YGR046W) encodes the mitochondrial CDP-diacylglycerol synthase (phosphatidate cytidylyltransferase, EC 2.7.7.41) of S. cerevisiae. It is a peripheral protein of the inner mitochondrial membrane facing the matrix and converts phosphatidic acid and CTP into CDP-diacylglycerol, the precursor used by Pgs1 for phosphatidylglycerol and hence cardiolipin synthesis; the ER CDP-DAG synthase Cds1 is not present in mitochondria. Purified Tam41 is active in vitro and needs Mg2+ (Co2+ and Cu2+ partly substitute). tam41 mutants lack cardiolipin and are temperature-sensitive, with secondary defects in TIM23/TIM22 protein import and respiratory supercomplex stability that were first interpreted as a direct translocator maintenance role but are explained by cardiolipin deficiency. Tam41 is unrelated in sequence to the CDS1-type integral-membrane synthases.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004605 phosphatidate cytidylyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000341245 (Tam41 family node, with S. pombe tam41 and rat Tamm41). Tam41 is the founding experimentally characterised member and appears in the with/from list because its own IDA grounds the node. Correct core activity. Supporting Evidence: PMID:23623749 Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM PMID:23623749 When we incubated NBD-PA and purified Tam41, NBD-PA was efficiently consumed |
| GO:0004605 phosphatidate cytidylyltransferase activity | IDA PMID:23623749 Tam41 is a CDP-diacylglycerol synthase required for cardioli... | ACCEPT | Summary: IDA (Tamura et al. 2013): purified Tam41 converted NBD-PA to CDP-DAG in vitro in a CTP- and Mg2+-dependent manner. Defines the core activity. Supporting Evidence: PMID:23623749 When we incubated NBD-PA and purified Tam41, NBD-PA was efficiently consumed PMID:23623749 Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM |
| GO:0004605 phosphatidate cytidylyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA from InterPro IPR015222 / RHEA:16229 / EC 2.7.7.41 mapping. Correct for Tam41. Supporting Evidence: PMID:23623749 Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM file:yeast/TAM41/TAM41-uniprot.txt Catalyzes the formation of CDP-diacylglycerol (CDP-DAG) from |
| GO:0004605 phosphatidate cytidylyltransferase activity | IMP PMID:23623749 Tam41 is a CDP-diacylglycerol synthase required for cardioli... | ACCEPT | Summary: IMP (Tamura et al. 2013): mitochondria lacking Tam41 lose CDP-DAG synthase activity, while Cds1 is ER-only, showing Tam41 provides the mitochondrial activity. Supporting Evidence: PMID:23623749 Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM PMID:23623749 Cds1 resides in the ER but not in mitochondria |
| GO:0005739 mitochondrion | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: HDA from the Huh et al. 2003 GFP localization screen. Correct but less specific than the matrix-side inner membrane location. Supporting Evidence: PMID:14562095 Global analysis of protein localization in budding yeast PMID:16943180 Tam41 is a peripheral inner mitochondrial membrane protein facing the matrix |
| GO:0005739 mitochondrion | HDA PMID:14690591 Assigning function to yeast proteins by integration of techn... | ACCEPT | Summary: HDA from Steinmetz/Hughes et al. 2003 integrated functional genomics (mitochondrial proteomics). Correct but general. Supporting Evidence: PMID:14690591 Assigning function to yeast proteins by integration of technologies PMID:16790493 Mmp37p is located in the mitochondrial matrix where it is peripherally associated with the inner membrane |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the Tam41 family node to mitochondrion (is_active_in). Correct; Tam41 acts at the matrix face of the inner membrane. Supporting Evidence: PMID:16943180 Tam41 is a peripheral inner mitochondrial membrane protein facing the matrix |
| GO:0005743 mitochondrial inner membrane | EXP PMID:23623749 Tam41 is a CDP-diacylglycerol synthase required for cardioli... | ACCEPT | Summary: EXP (UniProt, Tamura et al. 2013) for mitochondrial inner membrane. Tam41 is a peripheral inner-membrane protein facing the matrix, where it makes CDP-DAG from inner-membrane PA. Supporting Evidence: PMID:23623749 Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM PMID:16943180 Tam41 is a peripheral inner mitochondrial membrane protein facing the matrix |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (mitochondrion inner membrane; peripheral, matrix side). Consistent with the experimental data. Supporting Evidence: PMID:16943180 Tam41 is a peripheral inner mitochondrial membrane protein facing the matrix |
| GO:0005759 mitochondrial matrix | IDA PMID:16790493 Characterization of Mmp37p, a Saccharomyces cerevisiae mitoc... | ACCEPT | Summary: IDA (Gallas et al. 2006): Mmp37/Tam41 is in the matrix, peripherally associated with the inner membrane. Compatible with the inner-membrane annotation. Supporting Evidence: PMID:16790493 Mmp37p is located in the mitochondrial matrix where it is peripherally associated with the inner membrane |
| GO:0005759 mitochondrial matrix | IDA PMID:16943180 Identification of Tam41 maintaining integrity of the TIM23 p... | ACCEPT | Summary: IDA (Tamura et al. 2006): Tam41 is a peripheral inner-membrane protein facing the matrix (matrix compartment by protease protection/fractionation). Supporting Evidence: PMID:16943180 Tam41 is a peripheral inner mitochondrial membrane protein facing the matrix |
| GO:0016024 CDP-diacylglycerol biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000341245 to CDP-diacylglycerol biosynthetic process. Tam41 makes CDP-DAG directly; this is the process of its core activity. Supporting Evidence: PMID:23623749 Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM PMID:23623749 When we incubated NBD-PA and purified Tam41, NBD-PA was efficiently consumed |
| GO:0016024 CDP-diacylglycerol biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: IEA from UniPathway UPA00557 (CDP-diacylglycerol biosynthesis). Correct. Supporting Evidence: PMID:23623749 Tam41, a highly conserved mitochondrial maintenance protein, directly catalyzes the formation of CDP-DAG from PA in the mitochondrial IM |
| GO:0032049 cardiolipin biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000341245 to cardiolipin biosynthetic process. Tam41 supplies the CDP-DAG consumed by Pgs1 in the first committed step of cardiolipin synthesis, so it performs a step of the pathway. Supporting Evidence: PMID:23623749 The present findings unveil the missing step of the cardiolipin synthesis pathway in mitochondria PMID:19114592 we found that Tam41 is required for the biosynthesis of the dimeric phospholipid cardiolipin |
| GO:0032049 cardiolipin biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: IEA from InterPro IPR015222 (Tam41 family) to cardiolipin biosynthetic process. Correct for this family. Supporting Evidence: PMID:23623749 The present findings unveil the missing step of the cardiolipin synthesis pathway in mitochondria |
| GO:0032049 cardiolipin biosynthetic process | IGI PMID:20485265 A mitochondrial phosphatase required for cardiolipin biosynt... | ACCEPT | Summary: IGI (Osman et al. 2010) with GEP4-pathway genes: epistasis placed Tam41 in an early step of cardiolipin synthesis, later identified as CDP-DAG formation. Supporting Evidence: PMID:20485265 assign an essential function during early steps of CL synthesis to Tam41 |
| GO:0032049 cardiolipin biosynthetic process | IGI PMID:20485265 A mitochondrial phosphatase required for cardiolipin biosynt... | ACCEPT | Summary: IGI (Osman et al. 2010), second epistasis partner: as above, Tam41 acts upstream in cardiolipin synthesis. Supporting Evidence: PMID:20485265 assign an essential function during early steps of CL synthesis to Tam41 |
| GO:0032049 cardiolipin biosynthetic process | IMP PMID:19114592 The translocator maintenance protein Tam41 is required for m... | ACCEPT | Summary: IMP (Kutik et al. 2008): tam41 mitochondria lack cardiolipin, and the import/respiratory phenotypes are explained by this. Correct. Supporting Evidence: PMID:19114592 we found that Tam41 is required for the biosynthesis of the dimeric phospholipid cardiolipin PMID:19114592 The pleiotropic effects of the translocator maintenance protein on preprotein import and respiratory chain can be attributed to its role in biosynthesis of mitochondrial cardiolipin |
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Download this section (compressed HTML)Q: How does matrix-facing Tam41 access phosphatidic acid in the inner membrane, and which transfer system (e.g. Ups1-Mdm35) supplies the PA pool it uses?
Experiment: Reconstitute purified Tam41 with PA-containing liposomes of varying cardiolipin/PE content to test membrane binding and lipid-composition dependence of CDP-DAG synthesis.
Mitochondrial phosphatidate cytidylyltransferase (CDP-DAG synthase); required for cardiolipin biosynthesis; viability of null mutant is strain-dependent; mRNA is targeted to the bud; mutant displays defect in mitochondrial protein import, likely due to altered membrane lipid composition
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