Mitochondrial aspartate aminotransferase (AspAT, EC 2.6.1.1) of Schizosaccharomyces pombe (SPBC725.01, allelic with the classical glu1 locus), a pyridoxal 5'-phosphate-dependent class-I aminotransferase located in the mitochondrial matrix. It interconverts L-aspartate + 2-oxoglutarate and oxaloacetate + L-glutamate. The glu1 (glutamate-requiring) mutant carries a nonsense mutation in maa1 and cannot grow on ammonium as sole nitrogen source; growth is restored by maa1, weakly by multicopy yhm2 (the mitochondrial 2-oxoglutarate carrier), but not by the cytosolic isozyme caa1. The tested glutamate-requiring phenotype supports a glutamate-forming role for Maa1 during ammonium assimilation, distinct from the aspartate-biosynthetic role of Caa1. This genetic evidence does not measure a universal net reaction direction. It is also the expected matrix arm of the malate-aspartate shuttle.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: The broad molecular-function annotation is true; the characterized or conserved L-aspartate:2-oxoglutarate transaminase activity is the informative activity. Reason: Refine to L-aspartate:2-oxoglutarate transaminase activity, already supported elsewhere in this review. This is term specificity, not a rejection of the original evidence. Proposed replacements: L-aspartate:2-oxoglutarate transaminase activity Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from the mitochondrial AspAT clade (Arabidopsis, FB Got2, MGI Got2). maa1 is in PTHR11879:SF22 with the mitochondrial isozymes; the S. pombe genetics confirm it is a functional AspAT. Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; PMID:39502420 maa1 , encoding a mitochondrial aspartate aminotransferase, is the causative |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Rhea/EC mapping (RHEA:21824, EC 2.6.1.1) of the UniProt catalytic activity; correct. Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IMP PMID:39502420 Mitochondrial aspartate aminotransferase ( maa1 ) inactivati... | ACCEPT | Summary: Kitamura (2024) identified maa1 as the glu1 gene: a nonsense allele truncating Maa1 after residue 175 causes the glutamate requirement and is complemented by a single integrated maa1+ copy and by an opal suppressor. The MF is inferred from loss of the AspAT-dependent phenotype rather than an enzyme assay, but the curator call is sound. Supporting Evidence: PMID:39502420 maa1 , encoding a mitochondrial aspartate aminotransferase, is the causative PMID:39502420 Since this reaction can proceed in both directions, the same enzyme also supplies glutamate by catalyzing the reverse reaction. |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Manual ISS from chicken mitochondrial AspAT (P00508), a direct counterpart of maa1. Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Manual ISS from S. cerevisiae mitochondrial AspAT Aat1 (Q01802), the budding-yeast ortholog. Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; PMID:1482685 which is likely to be the yeast mitochondrial AspAT |
| GO:0005739 mitochondrion | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: Retain the supported mitochondrial localization alongside the existing matrix annotation. Reason: The native S. pombe localization screen (PMID:16823372) supports the organelle assignment; curated Maa1 matrix localization independently agrees. The screening evidence need not resolve matrix topology to establish a valid mitochondrion annotation. Retain the informative mitochondrion assertion under the root-organelle policy; existing mitochondrial matrix annotations are separate and are not substituted for this row. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins file:SCHPO/maa1/maa1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the supported mitochondrial localization alongside the existing matrix annotation. Reason: The PAINT-inherited mitochondrial claim is consistent with native S. pombe localization evidence (PMID:16823372) and the curated Maa1 matrix location. The previously recorded PANTHER:PTN000222845 provenance is not evidence of a granularity failure; no reconstruction of the ancestral placement or target-specific loss is asserted. Retain the informative mitochondrion assertion under the root-organelle policy; existing mitochondrial matrix annotations are separate and are not substituted for this row. Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the supported mitochondrial localization alongside the existing matrix annotation. Reason: The similarity-based mitochondrial claim agrees with native S. pombe localization evidence (PMID:16823372) and curated Maa1 matrix localization. Orthology supports the organelle assignment without implying that the transfer itself supplies a matrix-resolved native assay. Retain the informative mitochondrion assertion under the root-organelle policy; existing mitochondrial matrix annotations are separate and are not substituted for this row. Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | EXP PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: UniProt records Mitochondrion matrix with experimental evidence from the ORFeome study (ECO:0000269|PubMed:16823372). The matrix is where maa1 transaminates. Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell (SL-0170) mapping of the experimentally supported matrix location; correct. Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0006103 2-oxoglutarate metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: The aminotransferase directly consumes or produces 2-oxoglutarate in its core reaction. Reason: This is participation in 2-oxoglutarate metabolism through the enzyme chemistry, not an indirect phenotype; the broad process is appropriate because the physiological direction is context dependent. Supporting Evidence: PMID:39502420 However, mitochondrial Maa1 has a pivotal role in glutamate synthesis by promoting the reaction in an opposite direction file:SCHPO/maa1/maa1-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0006520 amino acid metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: The enzyme directly catalyzes amino-acid metabolism; the established reaction-specific process is more informative. Reason: Retain the biological claim and refine to the supported biosynthetic or catabolic processes already represented in this review. Proposed replacements: L-glutamate biosynthetic process Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0006531 aspartate metabolic process | ISS GO_REF:0000024 | MODIFY | Summary: Aspartate metabolism is correct, with more specific supported directional processes. Reason: Refine the broad process using the native biosynthetic role or the supported inherited catabolic direction; reversibility does not imply equal net flux in all conditions. Proposed replacements: L-aspartate catabolic process Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0006532 L-aspartate biosynthetic process | IC GO_REF:0000111 | KEEP AS NON CORE | Summary: PomBase IC (with GO:0004069) from GO-CAM gomodel:67c10cc400005826, where maa1 is part_of L-aspartate biosynthetic process in the matrix. The reaction is reversible and matrix aspartate is needed for shuttle export, so the term is not wrong; however Kitamura (2024) states that caa1 carries the major aspartate-forming flux and that maa1 acts mainly in the opposite, glutamate-forming direction. The glu1 mutant is rescued by glutamate but not by aspartate. Reason: Reversible enzyme; S. pombe genetics put maa1's main flux in glutamate formation, not aspartate synthesis. Supporting Evidence: PMID:39502420 The cytoplasmic Caa1 has a major role for this reaction in PMID:39502420 However, mitochondrial Maa1 has a pivotal role in glutamate synthesis by promoting the reaction in an opposite direction PMID:39502420 growth defects in this mutant may be related to glutamate, but not aspartate, shortage. |
| GO:0006533 L-aspartate catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for L-aspartate catabolic process from the mitochondrial AspAT clade (rat/human GOT2). In S. pombe this direction (aspartate + 2-oxoglutarate to oxaloacetate + glutamate) is the one Kitamura (2024) assigns as maa1's main physiological role, so the family inference fits the S. pombe data. Supporting Evidence: PMID:39502420 However, mitochondrial Maa1 has a pivotal role in glutamate synthesis by promoting the reaction in an opposite direction PMID:39502420 Since this reaction can proceed in both directions, the same enzyme also supplies glutamate by catalyzing the reverse reaction. |
| GO:0006536 glutamate metabolic process | ISS GO_REF:0000024 | MODIFY | Summary: Manual ISS (P00508) for glutamate metabolic process. For maa1 there is S. pombe-specific evidence for the more precise process: the maa1 nonsense (glu1) mutant needs glutamate for growth on ammonium, and maa1 supplies glutamate by running the transamination in the reverse direction. The enzyme itself forms the glutamate, so L-glutamate biosynthetic process is a participation (not merely necessity) term. Reason: S. pombe genetics support the specific child term L-glutamate biosynthetic process. Proposed replacements: L-glutamate biosynthetic process Supporting Evidence: PMID:39502420 However, mitochondrial Maa1 has a pivotal role in glutamate synthesis by promoting the reaction in an opposite direction PMID:39502420 Since this reaction can proceed in both directions, the same enzyme also supplies glutamate by catalyzing the reverse reaction. PMID:39502420 growth defects in this mutant may be related to glutamate, but not aspartate, shortage. |
| GO:0008483 transaminase activity | IEA GO_REF:0000002 | MODIFY | Summary: The broad molecular-function annotation is true; the characterized or conserved L-aspartate:2-oxoglutarate transaminase activity is the informative activity. Reason: Refine to L-aspartate:2-oxoglutarate transaminase activity, already supported elsewhere in this review. This is term specificity, not a rejection of the original evidence. Proposed replacements: L-aspartate:2-oxoglutarate transaminase activity Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0030170 pyridoxal phosphate binding | IEA GO_REF:0000002 | ACCEPT | Summary: Pyridoxal phosphate binding is integral to the aminotransferase catalytic mechanism. Reason: The cofactor-binding property is core to this enzyme, not peripheral merely because it is not an independent reaction. Direct target biochemical evidence, where available, and conserved PLP-dependent architecture support the claim. Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; |
| GO:0043490 malate-aspartate shuttle | IC GO_REF:0000111 | KEEP AS NON CORE | Summary: PomBase IC (with GO:0004069) from the GO-CAM malate-aspartate shuttle model, where maa1 is the matrix AspAT of the shuttle alongside odc1 carriers and mdh1. Mitochondrial AspAT is a canonical shuttle enzyme (S. cerevisiae aat1 deletion causes respiratory deficiency), but the shuttle has not been tested in S. pombe and the glu1 phenotype points to glutamate supply as maa1's dominant role. Reason: Plausible role by analogy; not the experimentally supported S. pombe function. Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt metabolite exchange between mitochondria and cytosol (By similarity). |
| GO:0043490 malate-aspartate shuttle | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA (ARBA00043538) rule for malate-aspartate shuttle; same assessment as the IC row. Reason: Family-level rule; shuttle not tested in S. pombe. Supporting Evidence: file:SCHPO/maa1/maa1-uniprot.txt metabolite exchange between mitochondria and cytosol (By similarity). |
Loading supporting content…
Download this section (compressed HTML)Q: Why does loss of maa1 cause a glutamate rather than an aspartate requirement, and does the glu1 phenotype reflect matrix glutamate supply for mitochondrial biosynthesis (e.g. arginine) or for whole-cell nitrogen assimilation?
Q: Should the PomBase GO-CAM part_of L-aspartate biosynthetic process for maa1 be complemented or replaced by L-glutamate biosynthetic process, given the glu1 genetics?
Experiment: Assay AspAT activity in purified mitochondria of wild type and glu1/maa1 strains and trace 15N from ammonium into glutamate and aspartate to establish the direction of maa1 flux.
Type: enzyme assay and isotope tracing
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)