Bcat2 encodes the mitochondrial branched-chain amino acid aminotransferase (BCATm), a pyridoxal 5'-phosphate-dependent class-IV aminotransferase (EC 2.6.1.42). After import into the mitochondrial matrix via an N-terminal transit peptide, it reversibly transfers the amino group of leucine, isoleucine or valine to 2-oxoglutarate, forming glutamate and the corresponding branched-chain 2-oxo acids. This is the first step of BCAA catabolism and feeds the branched-chain 2-oxo acid dehydrogenase complex, with which Bcat2 associates in a mitochondrial metabolon. Bcat2 is expressed in most peripheral tissues, with skeletal muscle a major site, but is largely absent from hepatocytes. Bcat2-deficient mice accumulate BCAAs and branched-chain keto acids in plasma and tissues and develop a maple syrup urine disease-like illness that responds to dietary BCAA restriction. Downstream consequences of its loss include increased energy expenditure, improved insulin sensitivity, exercise intolerance and, after adipose-specific deletion, increased browning of white fat.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based assignment of generic catalytic activity. Reason: True but uninformative; the class-IV aminotransferase signatures and mouse loss-of-function data support the specific branched-chain-amino-acid:2-oxoglutarate transaminase activity, which this review accepts. Proposed replacements: branched-chain-amino-acid:2-oxoglutarate transaminase activity Supporting Evidence: file:mouse/Bcat2/Bcat2-uniprot.txt SIMILARITY: Belongs to the class-IV pyridoxal-phosphate-dependent PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity |
| GO:0004084 branched-chain-amino-acid:2-oxoglutarate transaminase activity | IDA PMID:14755340 ENU mutagenesis identifies mice with mitochondrial branched-... | ACCEPT | Summary: Mouse Bcat2 has branched-chain-amino-acid:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0004084 branched-chain-amino-acid:2-oxoglutarate transaminase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Mouse Bcat2 has branched-chain-amino-acid:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Combined IEA (EC 2.6.1.42, InterPro BCAT family) is consistent with the mouse experimental evidence. Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0004084 branched-chain-amino-acid:2-oxoglutarate transaminase activity | IMP PMID:14755340 ENU mutagenesis identifies mice with mitochondrial branched-... | ACCEPT | Summary: Mouse Bcat2 has branched-chain-amino-acid:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0004084 branched-chain-amino-acid:2-oxoglutarate transaminase activity | ISO GO_REF:0000096 | ACCEPT | Summary: Mouse Bcat2 has branched-chain-amino-acid:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0004084 branched-chain-amino-acid:2-oxoglutarate transaminase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Mouse Bcat2 has branched-chain-amino-acid:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0005654 nucleoplasm | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Nucleoplasm location transferred from human BCAT2 by orthology. Reason: Mouse Bcat2 carries an N-terminal mitochondrial transit peptide, is found in mitochondria in mouse fractionation and organelle proteomics, and acts with BCKDH in the mitochondrial matrix. No mouse evidence places it in the nucleoplasm; the human source is a single-location observation not reflected in the PAINT mitochondrion node (PTN000214536). The nucleoplasm location should not be transferred as a property of the mouse protein. Propagation Review Root cause: SOURCE STALE OR MISSING Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:O15382 SOURCE STALE OR MISSING The human BCAT2 GOA snapshot cached in this repository (genes/human/BCAT2/BCAT2-goa.tsv) no longer carries a nucleoplasm annotation; the ISO row appears to transfer a retired or single-screen human location onto a mitochondrial matrix enzyme. Supporting Evidence: file:mouse/Bcat2/Bcat2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14755340}. PMID:14651853 we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver |
| GO:0005739 mitochondrion | HDA PMID:14651853 Integrated analysis of protein composition, tissue diversity... | ACCEPT | Summary: Bcat2 is a mitochondrial protein, imported via an N-terminal transit peptide. Reason: Supported in mouse by fractionation in the Bcat2 mutant study (UniProt ECO:0000269 to PMID:14755340) and by two independent mouse mitochondrial proteomic surveys. The IBA row derives from PAINT node PTN000214536, for which mouse Bcat2 is itself one of the seeds, so the IBA additionally states that mitochondrial location is inherited across the clade. Mitochondrial matrix is the more precise sublocation, accepted separately; mitochondrion is as precise as these particular evidence sources allow. Supporting Evidence: file:mouse/Bcat2/Bcat2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14755340}. PMID:14651853 we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver PMID:18614015 we performed mass spectrometry, GFP tagging, and machine learning to create a mitochondrial compendium of 1098 genes |
| GO:0005739 mitochondrion | HDA PMID:18614015 A mitochondrial protein compendium elucidates complex I dise... | ACCEPT | Summary: Bcat2 is a mitochondrial protein, imported via an N-terminal transit peptide. Reason: Supported in mouse by fractionation in the Bcat2 mutant study (UniProt ECO:0000269 to PMID:14755340) and by two independent mouse mitochondrial proteomic surveys. The IBA row derives from PAINT node PTN000214536, for which mouse Bcat2 is itself one of the seeds, so the IBA additionally states that mitochondrial location is inherited across the clade. Mitochondrial matrix is the more precise sublocation, accepted separately; mitochondrion is as precise as these particular evidence sources allow. Supporting Evidence: file:mouse/Bcat2/Bcat2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14755340}. PMID:14651853 we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver PMID:18614015 we performed mass spectrometry, GFP tagging, and machine learning to create a mitochondrial compendium of 1098 genes |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Bcat2 is a mitochondrial protein, imported via an N-terminal transit peptide. Reason: Supported in mouse by fractionation in the Bcat2 mutant study (UniProt ECO:0000269 to PMID:14755340) and by two independent mouse mitochondrial proteomic surveys. The IBA row derives from PAINT node PTN000214536, for which mouse Bcat2 is itself one of the seeds, so the IBA additionally states that mitochondrial location is inherited across the clade. Mitochondrial matrix is the more precise sublocation, accepted separately; mitochondrion is as precise as these particular evidence sources allow. Supporting Evidence: file:mouse/Bcat2/Bcat2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14755340}. PMID:14651853 we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver PMID:18614015 we performed mass spectrometry, GFP tagging, and machine learning to create a mitochondrial compendium of 1098 genes |
| GO:0005739 mitochondrion | IDA PMID:14755340 ENU mutagenesis identifies mice with mitochondrial branched-... | ACCEPT | Summary: Bcat2 is a mitochondrial protein, imported via an N-terminal transit peptide. Reason: Supported in mouse by fractionation in the Bcat2 mutant study (UniProt ECO:0000269 to PMID:14755340) and by two independent mouse mitochondrial proteomic surveys. The IBA row derives from PAINT node PTN000214536, for which mouse Bcat2 is itself one of the seeds, so the IBA additionally states that mitochondrial location is inherited across the clade. Mitochondrial matrix is the more precise sublocation, accepted separately; mitochondrion is as precise as these particular evidence sources allow. Supporting Evidence: file:mouse/Bcat2/Bcat2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14755340}. PMID:14651853 we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver PMID:18614015 we performed mass spectrometry, GFP tagging, and machine learning to create a mitochondrial compendium of 1098 genes |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Bcat2 is a mitochondrial protein, imported via an N-terminal transit peptide. Reason: Supported in mouse by fractionation in the Bcat2 mutant study (UniProt ECO:0000269 to PMID:14755340) and by two independent mouse mitochondrial proteomic surveys. The IBA row derives from PAINT node PTN000214536, for which mouse Bcat2 is itself one of the seeds, so the IBA additionally states that mitochondrial location is inherited across the clade. Mitochondrial matrix is the more precise sublocation, accepted separately; mitochondrion is as precise as these particular evidence sources allow. Supporting Evidence: file:mouse/Bcat2/Bcat2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14755340}. PMID:14651853 we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver PMID:18614015 we performed mass spectrometry, GFP tagging, and machine learning to create a mitochondrial compendium of 1098 genes |
| GO:0005739 mitochondrion | ISO GO_REF:0000096 | ACCEPT | Summary: Bcat2 is a mitochondrial protein, imported via an N-terminal transit peptide. Reason: Supported in mouse by fractionation in the Bcat2 mutant study (UniProt ECO:0000269 to PMID:14755340) and by two independent mouse mitochondrial proteomic surveys. The IBA row derives from PAINT node PTN000214536, for which mouse Bcat2 is itself one of the seeds, so the IBA additionally states that mitochondrial location is inherited across the clade. Mitochondrial matrix is the more precise sublocation, accepted separately; mitochondrion is as precise as these particular evidence sources allow. Supporting Evidence: file:mouse/Bcat2/Bcat2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14755340}. PMID:14651853 we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver PMID:18614015 we performed mass spectrometry, GFP tagging, and machine learning to create a mitochondrial compendium of 1098 genes |
| GO:0005739 mitochondrion | ISO GO_REF:0000096 | ACCEPT | Summary: Bcat2 is a mitochondrial protein, imported via an N-terminal transit peptide. Reason: Supported in mouse by fractionation in the Bcat2 mutant study (UniProt ECO:0000269 to PMID:14755340) and by two independent mouse mitochondrial proteomic surveys. The IBA row derives from PAINT node PTN000214536, for which mouse Bcat2 is itself one of the seeds, so the IBA additionally states that mitochondrial location is inherited across the clade. Mitochondrial matrix is the more precise sublocation, accepted separately; mitochondrion is as precise as these particular evidence sources allow. Supporting Evidence: file:mouse/Bcat2/Bcat2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14755340}. PMID:14651853 we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver PMID:18614015 we performed mass spectrometry, GFP tagging, and machine learning to create a mitochondrial compendium of 1098 genes |
| GO:0005739 mitochondrion | ISO GO_REF:0000119 | ACCEPT | Summary: Bcat2 is a mitochondrial protein, imported via an N-terminal transit peptide. Reason: Supported in mouse by fractionation in the Bcat2 mutant study (UniProt ECO:0000269 to PMID:14755340) and by two independent mouse mitochondrial proteomic surveys. The IBA row derives from PAINT node PTN000214536, for which mouse Bcat2 is itself one of the seeds, so the IBA additionally states that mitochondrial location is inherited across the clade. Mitochondrial matrix is the more precise sublocation, accepted separately; mitochondrion is as precise as these particular evidence sources allow. Supporting Evidence: file:mouse/Bcat2/Bcat2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14755340}. PMID:14651853 we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver PMID:18614015 we performed mass spectrometry, GFP tagging, and machine learning to create a mitochondrial compendium of 1098 genes |
| GO:0005759 mitochondrial matrix | IDA PMID:14755340 ENU mutagenesis identifies mice with mitochondrial branched-... | ACCEPT | Summary: Bcat2 is active in the mitochondrial matrix. Reason: Curator IDA from the mouse Bcat2 mutant study (full text not cached). Consistent with the mitochondrial transit peptide and with the endogenous BCAT2-BCKDH metabolon detected in mouse kidney mitochondria; BCKDH is a matrix complex. Supporting Evidence: file:mouse/Bcat2/Bcat2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14755340}. PMID:36443523 we provide evidence for the formation of a mitochondrial BCAA metabolon involving BCAT2 and branched-chain Ξ±-keto acid dehydrogenase |
| GO:0006550 L-isoleucine catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Bcat2 participates in L-isoleucine catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0006550 L-isoleucine catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: Bcat2 participates in L-isoleucine catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0006550 L-isoleucine catabolic process | IMP PMID:14755340 ENU mutagenesis identifies mice with mitochondrial branched-... | ACCEPT | Summary: Bcat2 participates in L-isoleucine catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0006550 L-isoleucine catabolic process | IMP PMID:17767905 Disruption of BCATm in mice leads to increased energy expend... | ACCEPT | Summary: Bcat2 participates in L-isoleucine catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0006550 L-isoleucine catabolic process | ISO GO_REF:0000096 | ACCEPT | Summary: Bcat2 participates in L-isoleucine catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0006551 L-leucine metabolic process | IMP PMID:14755340 ENU mutagenesis identifies mice with mitochondrial branched-... | MODIFY | Summary: Leucine metabolism is altered in Bcat2-deficient mice. Reason: Correct but less specific than the evidence supports: Bcat2 performs the first step of leucine degradation. The accepted L-leucine catabolic process term is the appropriate refinement. Proposed replacements: L-leucine catabolic process Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria |
| GO:0006551 L-leucine metabolic process | IMP PMID:17767905 Disruption of BCATm in mice leads to increased energy expend... | MODIFY | Summary: Leucine metabolism is altered in Bcat2-deficient mice. Reason: Correct but less specific than the evidence supports: Bcat2 performs the first step of leucine degradation. The accepted L-leucine catabolic process term is the appropriate refinement. Proposed replacements: L-leucine catabolic process Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria |
| GO:0006552 L-leucine catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: Bcat2 participates in L-leucine catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. PAINT propagated isoleucine and valine catabolic process from PTN000214535 but not leucine catabolic process; that omission is noted, but this row rests on mouse IMP data (all three BCAAs rise in the mutant) rather than on transfer, so it is accepted. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0006552 L-leucine catabolic process | IMP PMID:14755340 ENU mutagenesis identifies mice with mitochondrial branched-... | ACCEPT | Summary: Bcat2 participates in L-leucine catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. PAINT propagated isoleucine and valine catabolic process from PTN000214535 but not leucine catabolic process; that omission is noted, but this row rests on mouse IMP data (all three BCAAs rise in the mutant) rather than on transfer, so it is accepted. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0006574 L-valine catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Bcat2 participates in L-valine catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0006574 L-valine catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: Bcat2 participates in L-valine catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0006574 L-valine catabolic process | IMP PMID:14755340 ENU mutagenesis identifies mice with mitochondrial branched-... | ACCEPT | Summary: Bcat2 participates in L-valine catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0009081 branched-chain amino acid metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: Branched-chain amino acid metabolic process. Reason: True but general; mouse Bcat2 loss-of-function data establish a role specifically in BCAA catabolism (first step), which is accepted elsewhere in this review. Proposed replacements: branched-chain amino acid catabolic process Supporting Evidence: file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0009081 branched-chain amino acid metabolic process | IMP PMID:20237068 Alcohol-induced IGF-I resistance is ameliorated in mice defi... | MODIFY | Summary: Branched-chain amino acid metabolic process. Reason: True but general; mouse Bcat2 loss-of-function data establish a role specifically in BCAA catabolism (first step), which is accepted elsewhere in this review. Proposed replacements: branched-chain amino acid catabolic process Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:20237068 whereas the sustained elevation in plasma BCAA is not sufficient to ameliorate |
| GO:0009083 branched-chain amino acid catabolic process | IEA GO_REF:0000107 | ACCEPT | Summary: Bcat2 participates in branched-chain amino acid catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0009083 branched-chain amino acid catabolic process | IMP PMID:14755340 ENU mutagenesis identifies mice with mitochondrial branched-... | ACCEPT | Summary: Bcat2 participates in branched-chain amino acid catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0009083 branched-chain amino acid catabolic process | IMP PMID:17767905 Disruption of BCATm in mice leads to increased energy expend... | ACCEPT | Summary: Bcat2 participates in branched-chain amino acid catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0009083 branched-chain amino acid catabolic process | IMP PMID:35075301 BCAA-BCKA axis regulates WAT browning through acetylation of... | ACCEPT | Summary: Bcat2 participates in branched-chain amino acid catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0009083 branched-chain amino acid catabolic process | ISO GO_REF:0000096 | ACCEPT | Summary: Bcat2 participates in branched-chain amino acid catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0009083 branched-chain amino acid catabolic process | ISO GO_REF:0000119 | ACCEPT | Summary: Bcat2 participates in branched-chain amino acid catabolic process by catalysing its first, reversible transamination step in mitochondria. Reason: Bcat2 catalyses the first, transamination step of BCAA catabolism, so it performs part of the process (it is not merely required for it). Loss of Bcat2 in mice (ENU splice mutant, targeted knockout) raises plasma and tissue BCAAs and BCKAs and blocks reamination flux, establishing the role in vivo in this species. Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:17767905 we disrupted the BCATm gene, which encodes the enzyme catalyzing the first step in peripheral BCAA metabolism PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Loss of BCAT2 but not BCAT1 leads to accumulation of BCAAs and branched-chain Ξ±-keto acids (BCKAs) file:mouse/Bcat2/Bcat2-uniprot.txt Catalyzes the first reaction in the catabolism of the |
| GO:0009098 L-leucine biosynthetic process | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Leucine biosynthetic process transferred from rat Bcat2. Reason: The transamination is reversible, and BCKA reamination by BCAT2 is measurable in mouse tissues ([13C]-KIV to labelled valine is reduced in Bcat2-/- tissues). However, leucine is an essential amino acid in mammals; reamination only salvages pre-existing carbon skeletons and is not a leucine biosynthetic pathway. The reversible reaction is fully captured by the accepted transaminase activity terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: RGD:68948 UNRESOLVED Rat Bcat2 donor annotation not inspected in detail; whatever its basis, reamination of keto acids in mammals salvages carbon skeletons and is not de novo leucine biosynthesis, so the term is mis-scoped for both rodents. Supporting Evidence: PMID:36443523 Compared to WT tissues, Bcat2β/β had significantly reduced levels of Val_M+5 in most tissues, consistent with BCAT2 loss and no or minimal BCAT1 expression in these tissues |
| GO:0010817 regulation of hormone levels | IMP PMID:17767905 Disruption of BCATm in mice leads to increased energy expend... | MARK AS OVER ANNOTATED | Summary: Whole-body hormone level changes (insulin sensitivity) in BCATm knockout mice. Reason: The knockout shows improved glucose and insulin tolerance, a systemic consequence of elevated BCAAs/loss of peripheral BCAA catabolism. Bcat2 is a metabolic enzyme and does no part of hormone regulation itself; the phenotype is downstream and organismal. Supporting Evidence: PMID:17767905 remarkable improvements in glucose and insulin tolerance PMID:17767905 BCATm(-/-) mice exhibited elevated plasma BCAAs and decreased adiposity and body weight |
| GO:0050873 brown fat cell differentiation | IMP PMID:35075301 BCAA-BCKA axis regulates WAT browning through acetylation of... | KEEP AS NON CORE | Summary: Adipose Bcat2 deletion increases browning of inguinal WAT. Reason: Experimental in mouse (adipose-specific knockout). The acts_upstream_of_negative_effect qualifier is appropriate: Bcat2 supplies BCKAs whose acetyl-CoA is used to acetylate PRDM16, so its metabolic activity lies upstream of, rather than within, the differentiation program. Note the cells involved are inguinal WAT (beige) adipocytes. Supporting Evidence: PMID:35075301 mice with adipose tissue knockout of Bcat2, which converts BCAAs to branched-chain keto acids (BCKAs), are resistant to high-fat diet-induced obesity due to increased inguinal WAT browning and thermogenesis PMID:35075301 acetyl-CoA derived from BCKA suppresses WAT browning by acetylation of PR domain-containing protein 16 (PRDM16) at K915 |
| GO:0052654 L-leucine:2-oxoglutarate transaminase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Mouse Bcat2 has L-leucine:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0052654 L-leucine:2-oxoglutarate transaminase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Mouse Bcat2 has L-leucine:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0052654 L-leucine:2-oxoglutarate transaminase activity | ISO GO_REF:0000096 | ACCEPT | Summary: Mouse Bcat2 has L-leucine:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0052654 L-leucine:2-oxoglutarate transaminase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Mouse Bcat2 has L-leucine:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0052655 L-valine:2-oxoglutarate transaminase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Mouse Bcat2 has L-valine:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0052655 L-valine:2-oxoglutarate transaminase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Mouse Bcat2 has L-valine:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0052655 L-valine:2-oxoglutarate transaminase activity | ISO GO_REF:0000096 | ACCEPT | Summary: Mouse Bcat2 has L-valine:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0052655 L-valine:2-oxoglutarate transaminase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Mouse Bcat2 has L-valine:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0052656 L-isoleucine:2-oxoglutarate transaminase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Mouse Bcat2 has L-isoleucine:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0052656 L-isoleucine:2-oxoglutarate transaminase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Mouse Bcat2 has L-isoleucine:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0052656 L-isoleucine:2-oxoglutarate transaminase activity | ISO GO_REF:0000096 | ACCEPT | Summary: Mouse Bcat2 has L-isoleucine:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0052656 L-isoleucine:2-oxoglutarate transaminase activity | ISO GO_REF:0000119 | ACCEPT | Summary: Mouse Bcat2 has L-isoleucine:2-oxoglutarate transaminase activity, the core catalytic activity of the mitochondrial branched-chain aminotransferase. Reason: Experimentally established in mouse: the ENU Bcat2 splice-site mutant lacks BCAT-2 protein and BCAT enzyme activity and accumulates all three BCAAs, and Bcat2-/- tissues show the reduced glutamate/2-oxoglutarate ratio expected from loss of BCAA:2-oxoglutarate transamination. Direct kinetic characterisation of purified mouse protein has not been reported; substrate specificity for Leu, Ile and Val rests on the loss-of-function data plus orthology to rat and human BCAT2 (same SF39 subfamily, PAINT node PTN000214535). Mouse Bcat2 (O35855) is in PANTHER subfamily PTHR11825:SF39 (mitochondrial BCAT) together with human BCAT2 (O15382) and rat Bcat2; the cytosolic paralog BCAT1 is in a separate subfamily (SF70), so transfer is restricted to SF39 orthologs. Supporting Evidence: PMID:14755340 deficiency in both BCAT-2 protein and its enzyme activity PMID:14755340 We identified mice with marked elevation of blood branched-chain amino acids (BCAAs), ketoaciduria PMID:36443523 Bcat2β/β mice had significant decreases in the glutamate/Ξ±-KG ratios in heart, kidney, liver and spleen, consistent with the loss of BCAT2 activity PMID:9165094 When rat BCAT(m) is overexpressed in COS-1 cells, the protein exhibits BCAT activity and correct processing of the mitochondrial targeting sequence. file:mouse/Bcat2/Bcat2-uniprot.txt PTHR11825:SF39; BRANCHED-CHAIN-AMINO-ACID AMINOTRANSFERASE, MITOCHONDRIAL |
| GO:0097009 energy homeostasis | IMP PMID:17767905 Disruption of BCATm in mice leads to increased energy expend... | MARK AS OVER ANNOTATED | Summary: Increased energy expenditure in BCATm knockout mice. Reason: The knockout has increased energy expenditure attributed to a futile protein turnover cycle; this is an organismal consequence of disrupted BCAA catabolism, not participation of the enzyme in an energy-homeostasis mechanism. Supporting Evidence: PMID:17767905 The increased energy expenditure did not seem to be due to altered locomotor activity, uncoupling proteins, sympathetic activity, or thyroid hormones PMID:17767905 BCATm(-/-) mice exhibited elevated plasma BCAAs and decreased adiposity and body weight |
| GO:1990830 cellular response to leukemia inhibitory factor | IEP PMID:20439489 miRNA 34a, 100, and 137 modulate differentiation of mouse em... | MARK AS OVER ANNOTATED | Summary: Expression change of Bcat2 in ES cells upon LIF withdrawal (transcriptome comparison). Reason: IEP from a genome-wide comparison of undifferentiated vs differentiating ES cells. A transcript-level change during differentiation does not show that Bcat2 performs any part of a response to LIF; no functional role in LIF signalling has been reported. Supporting Evidence: PMID:20439489 We performed a systematic comparison of miRNA expression in undifferentiated vs. differentiating ESCs. |
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Download this section (compressed HTML)Q: What fraction of whole-body BCKA reamination in mouse is carried by Bcat2 versus Bcat1 in each tissue, and does metabolon formation with BCKDH channel the keto acids?
Q: Is the reported nucleoplasmic signal for the human ortholog relevant to mouse Bcat2, e.g. from an unprocessed or alternatively initiated product?
Experiment: Purify recombinant mature mouse Bcat2 and measure kinetics for Leu, Ile and Val in both transamination directions, with PLP occupancy and dimer state.
Hypothesis: Mouse Bcat2 has the same substrate specificity and kinetic parameters as rat and human BCAT2, so ortholog-derived specificity terms are valid for mouse.
Type: enzyme kinetics
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