GOT2 encodes the mitochondrial aspartate aminotransferase (mAspAT / mAST / GOT), a homodimeric, pyridoxal-5'-phosphate (PLP)-dependent class-I aminotransferase located in the mitochondrial matrix. Its principal reaction is the reversible transfer of the amino group between L-aspartate and 2-oxoglutarate to form oxaloacetate and L-glutamate (EC 2.6.1.1). PLP is bound covalently as a Schiff base to the active-site lysine (Lys-279 in the precursor numbering). GOT2 is the mitochondrial transaminase arm of the malate-aspartate shuttle, which transfers reducing equivalents (NADH) from the cytosol into mitochondria and maintains the intracellular NAD(H) redox balance; through the interconversion of aspartate, glutamate, oxaloacetate and 2-oxoglutarate it links amino-acid metabolism to the tricarboxylic acid cycle and to metabolite exchange between mitochondria and cytosol. Loss of GOT2 function causes an autosomal-recessive, treatable malate-aspartate-shuttle-related developmental and epileptic encephalopathy (DEE82), with impaired de novo serine biosynthesis. Beyond its core transaminase role, GOT2 is a moonlighting protein: as a plasma-membrane-associated fatty-acid-binding protein (FABPpm) it mediates cellular uptake of long-chain free fatty acids, and it possesses kynurenine aminotransferase activity (KAT4/KYAT4, EC 2.6.1.7), transaminating L-kynurenine to kynurenic acid. The cytosolic paralog is encoded by the separate gene GOT1. Serum mitochondrial-AST activity is used clinically as a marker of tissue (liver, heart) injury.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assignment of the defining aspartate aminotransferase molecular function. This is the core catalytic activity of GOT2 and is independently supported by direct assays (IDA/EXP) and the curated EC 2.6.1.1 reaction. Reason: Correct core molecular function; the PAN-GO family assignment matches the experimentally verified EC 2.6.1.1 activity of mitochondrial AST. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) localization to the mitochondrion, using the is_active_in qualifier. Correct and core: GOT2 is the mitochondrial AST isozyme (the more precise location is the mitochondrial matrix). Reason: Mitochondrion is the well-established site of action; corroborated by UniProt SUBCELL (Mitochondrion matrix), IDA and multiple proteomic datasets. |
| GO:0006533 L-aspartate catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic assignment of aspartate catabolism, reflecting the direction of the transamination that consumes L-aspartate (to oxaloacetate). A core metabolic role, also supported by IDA (PMID:2567216). Reason: GOT2 converts L-aspartate to oxaloacetate, the catabolic direction of the reversible transaminase reaction; consistent with experimental evidence. |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Root-level "catalytic activity" from InterPro. Correct but entirely uninformative given the specific aspartate aminotransferase activity is known. Reason: Superseded by the specific molecular function GO:0004069; a top-level grouping term that adds no information. |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of the core aspartate aminotransferase activity via combined IEA methods (Rhea/EC 2.6.1.1). Redundant with, and confirmed by, the experimental annotations. Reason: Correct core molecular function, consistent with the curated EC 2.6.1.1 catalytic activity. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic localization to the mitochondrial matrix from the UniProt Subcellular Location keyword. Correct and core; the matrix is the site of the malate-aspartate shuttle transaminase step. Reason: Consistent with the experimentally supported mitochondrial-matrix localization of mAST. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic localization to the plasma membrane from the UniProt Subcellular Location keyword (Cell membrane). Reflects the genuine moonlighting FABPpm pool of GOT2 at the plasma membrane, not the core mitochondrial-matrix location. Reason: A real, secondary localization: GOT2 translocates to the plasma membrane as FABPpm. Non-core relative to its mitochondrial matrix site; supported experimentally by PMID:9537447. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Cell membrane |
| GO:0006520 amino acid metabolic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Broad "amino acid metabolic process" from InterPro. True but generic; the specific aspartate/glutamate/2-oxoglutarate metabolic processes are annotated separately. Reason: High-level grouping term superseded by the more specific aspartate/glutamate metabolic-process annotations. |
| GO:0006533 L-aspartate catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA electronic annotation for aspartate catabolism, mirroring the direction of transamination that consumes L-aspartate. A core metabolic role, also supported by IBA and IDA (PMID:2567216). Reason: GOT2 converts L-aspartate to oxaloacetate, the catabolic direction; consistent with experimental evidence. |
| GO:0008483 transaminase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Parent "transaminase activity" from InterPro. Correct but less specific than the annotated L-aspartate:2-oxoglutarate transaminase activity. Reason: Grouping term superseded by the specific GO:0004069. |
| GO:0016212 L-kynurenine:2-oxoglutarate transaminase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic assignment (from EC 2.6.1.7 / Rhea) of kynurenine aminotransferase activity. A genuine secondary activity: GOT2 is kynurenine aminotransferase 4 (KAT4/KYAT4), transaminating L-kynurenine to kynurenate. Human support is by similarity to the pig ortholog (P00507) rather than direct assay. Reason: Real but non-primary moonlighting catalytic activity of this broad-specificity aminotransferase (AltName "Kynurenine aminotransferase 4"); human evidence is ISS/by-similarity, and it is a minor branch relative to the core aspartate reaction. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-kynurenine + 2-oxoglutarate = kynurenate + L-glutamate + |
| GO:0030170 pyridoxal phosphate binding | IEA GO_REF:0000002 | ACCEPT | Summary: PLP binding from InterPro. Core enzymatic feature: GOT2 is a PLP-dependent transaminase with pyridoxal 5'-phosphate bound covalently as a Schiff base to the active-site lysine (N6-(pyridoxal phosphate)lysine at position 279). Reason: Structurally and biochemically confirmed cofactor binding; UniProt records PLP as cofactor and the pyridoxal-phosphate lysine modification. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Name=pyridoxal 5'-phosphate |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | EXP PMID:26902786 Recombinant expression, purification and crystallographic st... | ACCEPT | Summary: Experimental (EXP) evidence for the core aspartate aminotransferase activity. Jiang et al. recombinantly expressed, purified and crystallized the mature human mAspAT and characterized its catalytic activity (optimum pH 8.5, 47.5 C; PDB 5AX8). Reason: Direct experimental confirmation of GOT2's core EC 2.6.1.1 activity in a recombinant human-protein study. Supporting Evidence: PMID:26902786 This enzyme plays a |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | EXP PMID:31422819 Bi-allelic GOT2 Mutations Cause a Treatable Malate-Aspartate... | ACCEPT | Summary: Experimental (EXP) evidence for the core aspartate aminotransferase activity. van Karnebeek et al. measured GOT2 enzyme activity, showing it is deficient in fibroblasts of individuals with bi-allelic GOT2 mutations (DEE82), and characterized loss-of-function variants. Reason: Directly links human GOT2 to the EC 2.6.1.1 activity via patient/variant enzymology. Supporting Evidence: PMID:31422819 activity was deficient in fibroblasts with bi-allelic mutations. GOT2, a member |
| GO:0043490 malate-aspartate shuttle | IMP PMID:37647199 The malate-aspartate shuttle is important for de novo serine... | ACCEPT | Summary: IMP for involvement in the malate-aspartate shuttle (MAS). Broeks et al. genetically disrupted each MAS component in HEK293 cells; GOT2 is the mitochondrial transaminase arm of the shuttle, which the study shows is important for de novo serine biosynthesis. A core physiological role. Reason: GOT2 is a canonical MAS enzyme (mitochondrial AST converts oxaloacetate to aspartate, completing the NADH-transfer cycle). The cached abstract foregrounds MDH1/OGC/serine, but the full-text MAS-component knockout panel includes GOT2; the annotation is biologically sound. Supporting Evidence: PMID:37647199 We genetically disrupted each MAS component to generate a panel of MAS-deficient |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput detection of GOT2 in a high-confidence human mitochondrial proteome. Correct and consistent with the core mitochondrial-matrix localization. Reason: Confirms mitochondrial localization; consistent with UniProt SUBCELL and IDA. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6784393 | ACCEPT | Summary: Reactome TAS localizing GOT2 to the mitochondrial matrix (in the reaction where the PXLP-K279-GOT2 dimer transaminates 4-hydroxy-L-glutamate to 4-hydroxy-2-oxoglutarate). Correct and core. Reason: Consistent with the established mitochondrial-matrix localization of mAST. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-70596 | ACCEPT | Summary: Reactome TAS (GOT2 dimer transaminates L-Asp) localizing the enzyme to the mitochondrial matrix. Correct and core. Reason: Consistent with mitochondrial-matrix localization; the Reactome reaction captures the core L-aspartate transamination. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-70613 | ACCEPT | Summary: Reactome TAS (GOT2 transaminates OA and L-Glu) localizing the enzyme to the mitochondrial matrix. Correct and core; captures the reverse (aspartate-synthesizing) direction. Reason: Consistent with mitochondrial-matrix localization and the reversible transaminase reaction. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: High-throughput MS detection of GOT2 in exosomes from prostatic secretions. Common for abundant metabolic enzymes; not a core functional localization. Reason: Secondary/incidental localization from exosome proteomics; the functional site is the mitochondrial matrix (with a moonlighting plasma-membrane pool). |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MARK AS OVER ANNOTATED | Summary: RNA binding from a high-throughput mRNA-interactome-capture study. Abundant mitochondrial metabolic enzymes are frequently recovered as incidental RNA-binders in such datasets; there is no evidence this is a physiological function of GOT2. Reason: Non-specific, high-throughput RNA-binding call with no mechanistic follow-up; not an informative or core molecular function for an aspartate aminotransferase. Retained (not removed) as it derives from an experimental HDA dataset. |
| GO:0005739 mitochondrion | HDA PMID:20833797 Phosphoproteome analysis of functional mitochondria isolated... | ACCEPT | Summary: High-throughput MS detection of GOT2 in a human muscle mitochondrial phosphoproteome. Correct and consistent with the core mitochondrial localization. Reason: Confirms mitochondrial localization; consistent with UniProt SUBCELL and other datasets. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: High-throughput MS detection of GOT2 in B-cell exosomes. Incidental localization of an abundant enzyme. Reason: Secondary exosomal localization; not core to GOT2 function. |
| GO:0019470 trans-4-hydroxy-L-proline catabolic process | TAS PMID:21998747 Structural and biochemical studies of human 4-hydroxy-2-oxog... | KEEP AS NON CORE | Summary: Author-statement (TAS, BHF-UCL) that mitochondrial aspartate aminotransferase is one of the four mitochondrial enzymes of the 4-hydroxy-L-proline degradation pathway, performing the conversion of 4-hydroxy-glutamate to 4-hydroxy-2-oxoglutarate. A genuine but minor, context-specific metabolic branch (the same GOT2 step is captured in Reactome R-HSA-6784393). Reason: Real participation in hydroxyproline catabolism via the broad substrate range of mAST, but peripheral to the core aspartate/glutamate transamination and malate-aspartate shuttle role. Supporting Evidence: PMID:21998747 aspartate aminotransferase (AspAT), and 4-hydroxy-2-oxoglutarate aldolase |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Core aspartate aminotransferase activity assigned by sequence similarity (to bovine P00508). Redundant with, and confirmed by, the experimental (IDA/EXP) evidence for the same function. Reason: Correct core molecular function. |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrial localization assigned by sequence similarity. Correct and core. Reason: Consistent with the well-established mitochondrial localization of mAST. |
| GO:0006103 2-oxoglutarate metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: 2-Oxoglutarate metabolism assigned by sequence similarity. Core: 2-oxoglutarate is the amino-group acceptor/donor in the AST reaction, linking to glutamate and the TCA cycle. Reason: 2-Oxoglutarate is a direct co-substrate/product of the aspartate aminotransferase reaction; a correct core metabolic-process annotation. |
| GO:0006531 aspartate metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Aspartate metabolism assigned by sequence similarity. Core: interconversion of L-aspartate and oxaloacetate is the defining reaction of the enzyme. Reason: Central to GOT2 function; L-aspartate is a primary substrate/product. |
| GO:0006536 glutamate metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: Glutamate metabolism assigned by sequence similarity. Core: L-glutamate is a primary product/substrate of the transamination. Reason: L-glutamate is a direct product/substrate of the AST reaction; a core metabolic-process annotation. |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IDA PMID:2182221 New automated measurement of mitochondrial aspartate aminotr... | ACCEPT | Summary: Direct-assay evidence for mitochondrial aspartate aminotransferase activity in the context of an automated serum method that distinguishes mitochondrial from cytosolic AST via protease-401 inactivation of the cytosolic form. Reason: Supports the core EC 2.6.1.1 activity of the mitochondrial isoenzyme (GOT2) and the GOT1/GOT2 biochemical distinction. Supporting Evidence: PMID:2182221 Total mitochondrial aspartate aminotransferase (EC 2.6.1.1) |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IDA PMID:2567216 Serum mitochondrial aspartate aminotransferase activity: not... | ACCEPT | Summary: Direct measurement of mitochondrial AST (mAST) catalytic activity in serum by an immunochemical method. Although the paper's clinical conclusion is negative (mAST not a useful alcohol marker), it directly assays the mitochondrial isoenzyme activity. Reason: Assays the catalytic activity of the mitochondrial isoenzyme (GOT2); supports the core molecular function. Supporting Evidence: PMID:2567216 we measured the activity of the mitochondrial |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IDA PMID:2731362 Effects of therapeutic coronary reperfusion on aspartate ami... | ACCEPT | Summary: Direct measurement of mitochondrial AST (m-AST) catalytic activity in patient serum, distinguished from the cytosolic isoenzyme. Supports the core enzymatic function of GOT2. Reason: Assays the catalytic activity of mitochondrial AST; consistent with the core molecular function. Supporting Evidence: PMID:2731362 mitochondrial AST (m-AST) |
| GO:0006533 L-aspartate catabolic process | IDA PMID:2567216 Serum mitochondrial aspartate aminotransferase activity: not... | ACCEPT | Summary: Aspartate catabolic process supported by direct assay of mitochondrial AST activity, which converts L-aspartate to oxaloacetate. A core metabolic role. Reason: GOT2 catalyzes the catabolic (aspartate-consuming) direction of the transamination; supported by the direct serum-activity measurement of the mitochondrial isoenzyme. Supporting Evidence: PMID:2567216 we measured the activity of the mitochondrial |
| GO:0005739 mitochondrion | IDA PMID:9537447 Ethanol up-regulates fatty acid uptake and plasma membrane e... | ACCEPT | Summary: Direct evidence for mitochondrial localization of mAspAT in HepG2 cells (Zhou et al.). Mitochondrial levels were unchanged by ethanol while plasma-membrane expression increased. Confirms the core mitochondrial localization. Reason: Experimental support for the mitochondrial localization of GOT2; consistent with the core matrix location. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix |
| GO:0005886 plasma membrane | IDA PMID:9537447 Ethanol up-regulates fatty acid uptake and plasma membrane e... | KEEP AS NON CORE | Summary: Direct evidence that mAspAT is expressed at the plasma membrane in HepG2 cells and that this pool increases with ethanol exposure, in parallel with fatty-acid uptake. Basis for the FABPpm moonlighting localization. Reason: A genuine, experimentally supported secondary localization (GOT2 as plasma-membrane FABPpm), distinct from and non-core relative to its mitochondrial-matrix site. Supporting Evidence: PMID:9537447 Plasma membrane mAspAT content also correlated with |
| GO:0015908 fatty acid transport | IEP PMID:9537447 Ethanol up-regulates fatty acid uptake and plasma membrane e... | KEEP AS NON CORE | Summary: IEP evidence that plasma-membrane mAspAT (FABPpm) mediates long-chain fatty-acid uptake: fatty-acid uptake Vmax increased in parallel with plasma-membrane mAspAT expression in ethanol-treated HepG2 cells. A genuine moonlighting role of GOT2. Reason: Well-supported secondary (moonlighting) function of the plasma-membrane pool of GOT2; UniProt states GOT2 "Facilitates cellular uptake of long-chain free fatty acids". Not the core mitochondrial transaminase function. Supporting Evidence: PMID:9537447 fatty acid uptake Vmax file:human/GOT2/GOT2-uniprot.txt Facilitates |
| GO:0045471 response to ethanol | IDA PMID:9537447 Ethanol up-regulates fatty acid uptake and plasma membrane e... | KEEP AS NON CORE | Summary: IDA that GOT2/mAspAT is up-regulated by ethanol: exposure produced a dose-dependent increase in mAspAT mRNA and increased plasma-membrane expression and export, linking ethanol to increased fatty-acid uptake (alcoholic fatty liver). Reason: A genuine, experimentally supported physiological-response context (ethanol induction and plasma-membrane translocation) rather than the core catalytic/shuttle function. Supporting Evidence: PMID:9537447 increase in mAspAT messenger RNA |
Loading supporting content…
Download this section (compressed HTML)Q: How is GOT2 partitioned between its mitochondrial-matrix transaminase pool and the plasma-membrane FABPpm pool, and what signals (beyond ethanol) control the translocation?
Q: What is the quantitative contribution of GOT2's kynurenine aminotransferase (KAT4) activity to kynurenic acid production relative to the other human KATs in different tissues?
Experiment: Isoform-/pool-resolved metabolic-flux analysis (13C tracing) in GOT2-knockout versus wild-type human cells to quantify its contribution to the malate-aspartate shuttle, NAD(H) redox balance and de novo serine biosynthesis.
Experiment: Structure-guided separation-of-function mutants that disrupt the long-chain-fatty-acid binding site without affecting transaminase activity, to test whether the FABPpm fatty-acid-uptake role is genuinely independent of catalysis.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)