Got1 (CG8430) encodes the cytoplasmic aspartate aminotransferase (glutamate oxaloacetate transaminase 1) of Drosophila melanogaster, a homodimeric pyridoxal 5'-phosphate-dependent class I aminotransferase. It reversibly transfers the amino group of L-aspartate to 2-oxoglutarate, interconverting aspartate/oxaloacetate and glutamate/2-oxoglutarate in the cytosol. Together with cytosolic malate dehydrogenase (Mdh1) and the mitochondrial isozyme Got2 it forms the cytosolic arm of the malate-aspartate shuttle that moves NADH reducing equivalents into mitochondria, and it links amino-acid and carbon metabolism, including the supply of glutamate. Like mammalian GOT1 it may also transaminate cysteine and related amino acids. GOT activity is differentially distributed in the adult central nervous system and musculature, and a low-activity Got1 allele was among the first mutations used to probe glutamate metabolism in flies.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Aspartate transaminase activity, phylogenetic inference. Reason: Got1 belongs to the aspartate aminotransferase family (PTHR11879) and carries the conserved PLP-binding lysine; the IBA is consistent with the direct enzymatic data. Supporting Evidence: file:DROME/Got1/Got1-uniprot.txt DR PANTHER; PTHR11879; ASPARTATE AMINOTRANSFERASE; 1. |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IDA PMID:3106567 A genetic analysis of glutamatergic function in Drosophila. | ACCEPT | Summary: Aspartate transaminase activity measured in fly tissues (Chase and Kankel 1987). Reason: GOT enzyme activity was assayed in Drosophila tissues and a Got1 mutant was analysed genetically; core activity. Supporting Evidence: PMID:3106567 we present the results of an initial genetic analysis of one enzymatic function, glutamate oxaloacetic transaminase (GOT) |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IDA PMID:823072 Genetic analysis of aspartate aminotransferase isozymes from... | ACCEPT | Summary: Aspartate aminotransferase isozyme GOT1 characterised electrophoretically and genetically (Grell 1976). Reason: Grell identified GOT1 as an aspartate aminotransferase isozyme, mapped Got1 and recovered a low-activity allele, directly linking the locus to the enzyme activity. Supporting Evidence: PMID:823072 At the locus of Got1 a mutation with low activity was recovered and designated Got1lo. |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Aspartate transaminase activity from combined IEA methods (EC 2.6.1.1). Reason: Consistent with experimental and phylogenetic evidence. Grell (1976) identified GOT1 as an aspartate aminotransferase isozyme and recovered a low-activity Got1 allele, and the protein carries the aspartate aminotransferase InterPro signature (IPR000796); the UniProt reaction line itself is an ARBA prediction and is not cited. Supporting Evidence: PMID:823072 At the locus of Got1 a mutation with low activity was recovered and designated Got1lo. file:DROME/Got1/Got1-uniprot.txt DR InterPro; IPR000796; Asp_trans. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: Cytoplasm from UniProt subcellular-location mapping. Reason: Got1 is the cytoplasmic isozyme; correct but less specific, so MODIFY to cytosol, which Got1 already carries (HDA, IBA, IDA). Proposed replacements: cytosol Supporting Evidence: file:DROME/Got1/Got1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005777 peroxisome | ISM PMID:22758915 An inventory of peroxisomal proteins and pathways in Drosoph... | UNDECIDED | Summary: Peroxisome, from a computational inventory of predicted peroxisomal proteins (Faust et al. 2012). Reason: The annotation is a sequence-based prediction (ISM). Got1 ends in a weak, non-canonical C-terminal tripeptide and the inventory paper experimentally confirmed only five of its predicted peroxisomal proteins; no data show Got1 in fly peroxisomes, while direct and high-throughput data place it in the cytosol. Insufficient evidence to accept or reject. Supporting Evidence: PMID:22758915 The subcellular localization of five of these predicted peroxisomal proteins was confirmed. |
| GO:0005829 cytosol | HDA PMID:25294944 Subcellular localisations of the CPTI collection of YFP-tagg... | ACCEPT | Summary: Cytosol from the CPTI YFP protein-trap localisation screen. Reason: High-throughput YFP-trap localisation consistent with the cytoplasmic isozyme. Supporting Evidence: PMID:25294944 Here, we characterise the subcellular localisations and expression patterns of these insertions, called the CPTI lines, in Drosophila embryos. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Cytosol, phylogenetic inference. Reason: PANTHER places Got1 in the GOT1 subfamily (PTHR11879:SF55), separate from the mitochondrial subfamily (SF22) that holds Got2; the IBA node (PTN000222846) is seeded by mouse Got1 and yeast AAT2, cytosolic isozymes. The quoted classification supports subfamily membership only; the cytosol location itself rests on the PAINT node and, for the fly protein, on the HDA YFP-trap row (PMID:25294944). The UniProt name and the ARBA-derived SUBCELLULAR LOCATION line are not cited as evidence. Supporting Evidence: file:DROME/Got1/Got1-uniprot.txt DR PANTHER; PTHR11879:SF55; GLUTAMATE OXALOACETATE TRANSAMINASE 1, ISOFORM B; 1. |
| GO:0005829 cytosol | IDA PMID:3106567 A genetic analysis of glutamatergic function in Drosophila. | ACCEPT | Summary: Cytosol, from the Chase and Kankel (1987) study of fly GOT isozymes. Reason: Core location of the cytoplasmic isozyme; curators had the full text. Supporting Evidence: PMID:3106567 spatial and temporal distribution of enzymatic activities thought to be important in the regulation of transmitter-glutamate pools |
| GO:0006094 gluconeogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Gluconeogenesis, transferred from mammalian GOT1. Reason: Cytosolic AST can supply oxaloacetate for phosphoenolpyruvate carboxykinase in gluconeogenic tissues of mammals; plausible in the fly fat body but not demonstrated, and a peripheral contribution rather than the enzyme's defining role. Supporting Evidence: file:DROME/Got1/Got1-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0006103 2-oxoglutarate metabolic process | IDA PMID:3106567 A genetic analysis of glutamatergic function in Drosophila. | ACCEPT | Summary: 2-oxoglutarate metabolic process (Chase and Kankel 1987). Reason: 2-Oxoglutarate is a direct substrate/product of the transamination; correct. The cached abstract of the source paper (Chase and Kankel 1987) shows only that GOT activity was assayed and genetically analysed; the curators had the full text. Grell (1976) independently identifies GOT1 as an aspartate aminotransferase, whose reaction consumes or forms 2-oxoglutarate. Supporting Evidence: PMID:3106567 we present the results of an initial genetic analysis of one enzymatic function, glutamate oxaloacetic transaminase (GOT) PMID:823072 The aspartate aminotransferases (designated GOT1 and GOT2) are two enzymes of Drosophila melanogaster |
| GO:0006103 2-oxoglutarate metabolic process | IDA PMID:823072 Genetic analysis of aspartate aminotransferase isozymes from... | ACCEPT | Summary: 2-oxoglutarate metabolic process (Grell 1976). Reason: Follows directly from the demonstrated aspartate aminotransferase activity. Supporting Evidence: PMID:823072 The aspartate aminotransferases (designated GOT1 and GOT2) are two enzymes of Drosophila melanogaster |
| GO:0006107 oxaloacetate metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Oxaloacetate metabolic process, transferred by sequence similarity. Reason: Oxaloacetate is a direct product/substrate of the aspartate aminotransferase reaction. Grell (1976) identifies GOT1 as an aspartate aminotransferase isozyme and Got1 carries the aspartate aminotransferase InterPro signature (IPR000796); the process follows from that activity. Supporting Evidence: PMID:823072 The aspartate aminotransferases (designated GOT1 and GOT2) are two enzymes of Drosophila melanogaster file:DROME/Got1/Got1-uniprot.txt DR InterPro; IPR000796; Asp_trans. |
| GO:0006520 amino acid metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: Amino acid metabolic process from InterPro. Reason: Correct but a general process for an aminotransferase; MODIFY to the specific aspartate/glutamate processes supported by enzyme assays, L-aspartate catabolic process and L-glutamate biosynthetic process, both already annotated to Got1 (GO:0006533: IDA; GO:0097054: IDA). Proposed replacements: L-aspartate catabolic process L-glutamate biosynthetic process Supporting Evidence: file:DROME/Got1/Got1-uniprot.txt DR InterPro; IPR000796; Asp_trans. |
| GO:0006532 L-aspartate biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: L-aspartate biosynthetic process, phylogenetic inference. Reason: The reaction is reversible and AST is the main route of aspartate formation from oxaloacetate; appropriate family-level inference. Support is the fly enzyme identity (Grell 1976) and membership of the aspartate aminotransferase family (PANTHER PTHR11879); the direction in vivo is inferred from the family, not shown for Got1. Supporting Evidence: PMID:823072 The aspartate aminotransferases (designated GOT1 and GOT2) are two enzymes of Drosophila melanogaster file:DROME/Got1/Got1-uniprot.txt DR PANTHER; PTHR11879; ASPARTATE AMINOTRANSFERASE; 1. |
| GO:0006533 L-aspartate catabolic process | IDA PMID:3106567 A genetic analysis of glutamatergic function in Drosophila. | ACCEPT | Summary: L-aspartate catabolic process (Chase and Kankel 1987). Reason: Transamination of aspartate to oxaloacetate; consistent with measured GOT activity. Supporting Evidence: PMID:3106567 glutamate oxaloacetic transaminase |
| GO:0006533 L-aspartate catabolic process | IDA PMID:823072 Genetic analysis of aspartate aminotransferase isozymes from... | ACCEPT | Summary: L-aspartate catabolic process (Grell 1976). Reason: Follows from the demonstrated activity. Supporting Evidence: PMID:823072 The aspartate aminotransferases (designated GOT1 and GOT2) are two enzymes of Drosophila melanogaster |
| GO:0006538 L-glutamate catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: L-glutamate catabolic process, transferred by sequence similarity. Reason: In the reverse direction AST consumes glutamate, but the cytosolic isozyme in the malate-aspartate shuttle predominantly forms glutamate from aspartate and 2-oxoglutarate; the catabolic direction is a minor aspect. Supporting Evidence: file:DROME/Got1/Got1-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0008483 transaminase activity | IEA GO_REF:0000002 | MODIFY | Summary: Transaminase activity from InterPro. Reason: Correct parent; MODIFY to L-aspartate:2-oxoglutarate transaminase activity, which Got1 already carries (IBA, IDA, IEA). Proposed replacements: L-aspartate:2-oxoglutarate transaminase activity Supporting Evidence: file:DROME/Got1/Got1-uniprot.txt DR InterPro; IPR000796; Asp_trans. |
| GO:0030170 pyridoxal phosphate binding | IEA GO_REF:0000002 | ACCEPT | Summary: Pyridoxal phosphate binding from InterPro. Reason: AST is a PLP-dependent enzyme; Got1 carries the PLP-dependent transferase InterPro signature (IPR015424) and the class I/II aminotransferase Pfam domain (PF00155). The UniProt COFACTOR line is an ARBA prediction and is not cited. Supporting Evidence: file:DROME/Got1/Got1-uniprot.txt DR InterPro; IPR015424; PyrdxlP-dep_Trfase. file:DROME/Got1/Got1-uniprot.txt DR Pfam; PF00155; Aminotran_1_2; 1. |
| GO:0043490 malate-aspartate shuttle | ISS GO_REF:0000024 | ACCEPT | Summary: Malate-aspartate shuttle, transferred by sequence similarity. Reason: Cytosolic AST, with cytosolic MDH and the mitochondrial isozymes, forms the conserved malate-aspartate shuttle; Got1 is the cytosolic AST of the fly. The pathway description is Reactome's human model, where cytosolic aspartate is transaminated to glutamate; Got1 is placed in it by orthology (its record cross-references the fly Reactome pathway R-DME-9856872) and by membership of the GOT1 subfamily (PANTHER SF55). Participation in the shuttle has not been shown experimentally in flies. Supporting Evidence: Reactome:R-HSA-9856872 At the same time, aspartate (L-Asp) gets exported and transaminated to glutamate (L-Glu) file:DROME/Got1/Got1-uniprot.txt DR Reactome; R-DME-9856872; Malate-aspartate shuttle. file:DROME/Got1/Got1-uniprot.txt DR PANTHER; PTHR11879:SF55; GLUTAMATE OXALOACETATE TRANSAMINASE 1, ISOFORM B; 1. |
| GO:0047801 L-cysteine:2-oxoglutarate transaminase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: L-cysteine transaminase activity from Rhea/EC mapping. Reason: Mammalian cytosolic AST is the cytosolic cysteine aminotransferase and the fly orthologue probably shares this side activity, but it has not been shown in Drosophila and is secondary to aspartate transamination. Supporting Evidence: file:DROME/Got1/Got1-uniprot.txt Reaction=L-cysteine + 2-oxoglutarate = 2-oxo-3-sulfanylpropanoate + L- |
| GO:0097054 L-glutamate biosynthetic process | IDA PMID:3106567 A genetic analysis of glutamatergic function in Drosophila. | ACCEPT | Summary: L-glutamate biosynthetic process (Chase and Kankel 1987). Reason: AST forms glutamate from 2-oxoglutarate; the paper studied GOT as a regulator of transmitter glutamate pools. Supporting Evidence: PMID:3106567 enzymatic activities thought to be important in the regulation of transmitter-glutamate pools |
| GO:0120554 (2S)-2-aminobutanoate:2-oxoglutarate transaminase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: (2S)-2-aminobutanoate transaminase activity from Rhea mapping. Reason: A side activity documented for mammalian GOT1; not studied in flies and not a core role. Supporting Evidence: file:DROME/Got1/Got1-uniprot.txt Reaction=(2S)-2-aminobutanoate + 2-oxoglutarate = 2-oxobutanoate + L- |
| GO:0120554 (2S)-2-aminobutanoate:2-oxoglutarate transaminase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: (2S)-2-aminobutanoate transaminase activity transferred from human GOT1. Reason: Same as the electronic annotation; plausible conserved side activity. Supporting Evidence: file:DROME/Got1/Got1-uniprot.txt Reaction=(2S)-2-aminobutanoate + 2-oxoglutarate = 2-oxobutanoate + L- |
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Download this section (compressed HTML)Q: Does Got1 contribute to neurotransmitter glutamate supply in glutamatergic neurons (for example DN1 clock neurons), as opposed to the mitochondrial Got2?
Experiment: Measure cytosolic NADH/NAD+ (e.g. with a Peredox-type sensor) and aspartate levels in Got1 mutant fat body or muscle to test its contribution to the malate-aspartate shuttle in vivo.
Glutamate oxaloacetate transaminase 1 (Got1) encodes a cytosolic enzyme that catalyzes the interconversion of L-aspartate and alpha-ketoglutarate to oxaloacetate and L-glutamate. It is involved in glutamate and aspartate biosynthesis, gluconeogenesis and the malate-aspartate shuttle.
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