DBT

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Mitochondrial localization is sound; the matrix sub-compartment is recorded separately. Reason: The actual PTHR43178 tree places human DBT below PTN000567862 and the literal mitochondrial IBD. Its current descendant evidence includes human localization, without any circularity from the target appearing among donors. The 482-residue target alignment carries the documented S384G variant rather than an exact canonical sequence; this is not evidence of lost mitochondrial targeting. GO:0005759 is a verified descendant of this broad compartment, so the existing matrix assertions provide the more specific representation. Under the root-organelle policy the mitochondrion term is informative in its own right and is kept beside the matrix rows rather than marked too general. Supporting Evidence: GO_REF:0000033 PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0043754 dihydrolipoamide branched chain acyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: DBT performs the conserved branched-chain acyltransferase step. Reason: The literal GO:0043754 IBD at PTN001139778 lies on the human lineage in the reconstructed family tree. Its plant, mouse and bovine sources have current exact-term experimental assertions. This phylogenetic placement agrees with the human E2 architecture and chemistry; it is not a pairwise donor-count argument. Supporting Evidence: GO_REF:0000033 PMID:3593587 file:human/DBT/DBT-uniprot.txt Within this complex, the catalytic function of this enzyme is to accept, and to transfer to coenzyme A, acyl groups that are generated by the branched-chain alpha-keto acid decarboxylase component. file:human/DBT/DBT-uniprot.txt DR InterPro; IPR001078; 2-oxoacid_DH_actylTfrase.
GO:0160157 branched-chain alpha-ketoacid dehydrogenase complex	IBA GO_REF:0000033	ACCEPT	Summary: DBT is the E2 component of the branched-chain alpha-ketoacid dehydrogenase complex. Reason: The exact complex IBD at PTN000567862 is ancestral to human DBT, and its human and bovine descendant evidence includes direct complex assertions. Human complex purification and E2-specific structural/biochemical evidence independently support membership. Supporting Evidence: GO_REF:0000033 PMID:3593587 PMID:22291014 file:human/DBT/DBT-uniprot.txt It is organized around E2, a 24-meric cubic core composed of DBT
GO:0005759 mitochondrial matrix	IEA GO_REF:0000120	ACCEPT	Summary: The mature DBT E2 enzyme acts in the mitochondrial matrix. Reason: The literal combined mapping includes ARBA00028628, mouse P53395 and mitochondrial-matrix location SL-0170. The actual rule has a matching target branch, the mouse record has a direct matrix assertion, and the mature human E2 is a constituent of the matrix BCKDH complex. MitoCoP membrane-association classification does not negate matrix residence. Supporting Evidence: GO_REF:0000120 PMID:34800366 file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0016746 acyltransferase activity	IEA GO_REF:0000002	TOO GENERAL	Summary: Acyltransferase activity is true but less specific than the retained DBT transacylase activity. Reason: All three literal InterPro sources match the human sequence and map to acyltransferase activity, including the catalytic and peripheral subunit-binding domains. Current typed ancestry places the existing accepted GO:0043754 below this term. The positive mapping is retained as evidence; it is not an overstatement of enzyme chemistry. Supporting Evidence: GO_REF:0000002 PMID:3593587 file:human/DBT/DBT-uniprot.txt DR InterPro; IPR001078; 2-oxoacid_DH_actylTfrase. file:human/DBT/DBT-uniprot.txt Within this complex, the catalytic function of this enzyme is to accept, and to transfer to coenzyme A, acyl groups that are generated by the branched-chain alpha-keto acid decarboxylase component.
GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups	IEA GO_REF:0000117	TOO GENERAL	Summary: The broad non-amino-acyl acyltransferase term is entailed by the specific E2 activity. Reason: ARBA00027717 has matching current branches for the target. The mapped broad activity is chemically correct, but existing accepted GO:0043754 is a verified descendant and already specifies the branched-chain lipoyl transfer reaction. Supporting Evidence: GO_REF:0000117 PMID:3593587 file:human/DBT/DBT-uniprot.txt DR InterPro; IPR001078; 2-oxoacid_DH_actylTfrase. file:human/DBT/DBT-uniprot.txt Within this complex, the catalytic function of this enzyme is to accept, and to transfer to coenzyme A, acyl groups that are generated by the branched-chain alpha-keto acid decarboxylase component.
GO:0043754 dihydrolipoamide branched chain acyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: The combined electronic sources identify DBT branched-chain acyltransferase activity. Reason: The original mouse/Ensembl, EC and three Rhea sources agree with the specific E2 reaction. The current curated catalytic objects distinguish isobutyryl, isovaleryl and 2-methylbutyryl chemistry. Human complex kinetics support the substrate range, while the E2 domain and component assignment distinguish transacylation from E1 decarboxylation and E3 NAD reduction. Supporting Evidence: GO_REF:0000120 PMID:3593587 PMID:11839747 file:human/DBT/DBT-uniprot.txt Within this complex, the catalytic function of this enzyme is to accept, and to transfer to coenzyme A, acyl groups that are generated by the branched-chain alpha-keto acid decarboxylase component. file:human/DBT/DBT-uniprot.txt DR InterPro; IPR001078; 2-oxoacid_DH_actylTfrase.
GO:0120552 branched-chain alpha-keto acid decarboxylation to branched-chain acyl-CoA	IEA GO_REF:0000117	ACCEPT	Summary: DBT directly performs transacylation within the three-reaction branched-chain ketoacid conversion. Reason: The current GO:0120552 definition explicitly includes E1 decarboxylation, E2 transfer to CoA and E3 reoxidation. DBT catalyzes the second step, so this is performed participation. The retained, committed GOA snapshot contains the ARBA00095351 assertion, and the inspected current rule has a matching target branch. This assessment preserves that source object; it does not infer NAD-dependent DBT molecular activity. Supporting Evidence: GO_REF:0000117 PMID:3593587 NAD and CoASH were absolutely required for the reaction. PMID:3593587 The BCKADH effectively oxidized all of KIV, KIC, and KMV, yielding apparent Km values in the range of 14-17 microM for those alpha-keto acids.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: Uninformative bare protein binding from BioPlex 2.0 AP-MS; removed under the protein-binding policy. Reason: Bare GO:0005515 protein binding is removed under the project's protein-binding policy because it names no informative molecular function. Removal does not dispute the reported affinity-purification association. The partners recorded for this source do not share a narrower functional class to MODIFY to; DBT's informative interaction (PPM1K docking) is captured separately on the PMID:22291014 row. Supporting Evidence: PMID:28514442 BioPlex 2.0 (Biophysical Interactions of ORFeome-derived complexes), which uses robust affinity purification-mass spectrometry methodology to elucidate protein interaction networks
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Uninformative bare protein binding from BioPlex 3.0 AP-MS; removed under the protein-binding policy. Reason: Bare GO:0005515 protein binding is removed under the project's protein-binding policy because it names no informative molecular function. Removal does not dispute the reported affinity-purification association. The partners recorded for this source do not share a narrower functional class to MODIFY to; DBT's informative interaction (PPM1K docking) is captured separately on the PMID:22291014 row. Supporting Evidence: PMID:33961781 The first, BioPlex 3.0, results from affinity purification of 10,128 human proteins-half the proteome-in 293T cells and includes 118,162 interactions among 14,586 proteins.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	REMOVE	Summary: Uninformative bare protein binding from the 2025 U2OS AP-MS map; removed under the protein-binding policy. Reason: Bare GO:0005515 protein binding is removed under the project's protein-binding policy because it names no informative molecular function. Removal does not dispute the reported affinity-purification association. The partners recorded for this source do not share a narrower functional class to MODIFY to; DBT's informative interaction (PPM1K docking) is captured separately on the PMID:22291014 row. Supporting Evidence: PMID:40205054 joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells
GO:0006550 L-isoleucine catabolic process	IEA GO_REF:0000107	ACCEPT	Summary: DBT transacylation is a core step in isoleucine catabolism. Reason: The literal mouse P53395/Ensembl source has an exact-term experimental assertion, and human liver BCKDH assays measure the corresponding branched-chain ketoacid substrate. E2 supplies the shared acyltransferase step. Use of three related substrates is a central property of this enzyme, not a reason to demote each substrate pathway to a peripheral role. Supporting Evidence: GO_REF:0000107 PMID:3593587 The BCKADH effectively oxidized all of KIV, KIC, and KMV, yielding apparent Km values in the range of 14-17 microM for those alpha-keto acids. Reactome:R-HSA-70895 Isovaleryl-CoA is produced from leucine by these two reactions, alpha-methylbutyryl-CoA from isoleucine, and isobutyryl-CoA from valine.
GO:0006552 L-leucine catabolic process	IEA GO_REF:0000107	ACCEPT	Summary: DBT transacylation is a core step in leucine catabolism. Reason: The literal mouse P53395/Ensembl source has an exact-term experimental assertion, and human liver BCKDH assays measure the corresponding branched-chain ketoacid substrate. E2 supplies the shared acyltransferase step. Use of three related substrates is a central property of this enzyme, not a reason to demote each substrate pathway to a peripheral role. Supporting Evidence: GO_REF:0000107 PMID:3593587 The BCKADH effectively oxidized all of KIV, KIC, and KMV, yielding apparent Km values in the range of 14-17 microM for those alpha-keto acids. Reactome:R-HSA-70895 Isovaleryl-CoA is produced from leucine by these two reactions, alpha-methylbutyryl-CoA from isoleucine, and isobutyryl-CoA from valine.
GO:0006574 L-valine catabolic process	IEA GO_REF:0000107	ACCEPT	Summary: DBT transacylation is a core step in valine catabolism. Reason: The literal mouse P53395/Ensembl source has an exact-term experimental assertion, and human liver BCKDH assays measure the corresponding branched-chain ketoacid substrate. E2 supplies the shared acyltransferase step. Use of three related substrates is a central property of this enzyme, not a reason to demote each substrate pathway to a peripheral role. Supporting Evidence: GO_REF:0000107 PMID:3593587 The BCKADH effectively oxidized all of KIV, KIC, and KMV, yielding apparent Km values in the range of 14-17 microM for those alpha-keto acids. Reactome:R-HSA-70895 Isovaleryl-CoA is produced from leucine by these two reactions, alpha-methylbutyryl-CoA from isoleucine, and isobutyryl-CoA from valine.
GO:0009083 branched-chain amino acid catabolic process	IEA GO_REF:0000107	ACCEPT	Summary: DBT performs a shared catalytic step in branched-chain amino-acid catabolism. Reason: The original automatic orthology source is rat B2GV15, whose complete current record retains experimental evidence for this pathway. This broad pathway describes the established shared physiological role of the enzyme, while the three substrate-specific existing annotations retain the individual branches. No additional coverage or new process is claimed from the broader term. Supporting Evidence: GO_REF:0000107 Reactome:R-HSA-70895 irreversible oxidative decarboxylation by the branched-chain ketoacid dehydrogenase complex PMID:3593587 The BCKADH effectively oxidized all of KIV, KIC, and KMV, yielding apparent Km values in the range of 14-17 microM for those alpha-keto acids.
GO:0009083 branched-chain amino acid catabolic process	TAS Reactome:R-HSA-70895	ACCEPT	Summary: The Reactome pathway places DBT chemistry in the common early steps of branched-chain amino-acid breakdown. Reason: The current pathway describes transamination followed by oxidative decarboxylation of all three branched-chain ketoacids. Its component reactions include the E2 transfer step. This is direct chemical participation in the shared pathway, not merely membership in a substrate set. Supporting Evidence: Reactome:R-HSA-9859163 Reactome:R-HSA-70895 irreversible oxidative decarboxylation by the branched-chain ketoacid dehydrogenase complex PMID:3593587 The BCKADH effectively oxidized all of KIV, KIC, and KMV, yielding apparent Km values in the range of 14-17 microM for those alpha-keto acids. file:human/DBT/DBT-deep-research-falcon.md Biallelic loss-of-function mutations in the DBT gene cause MSUD type II (OMIM 248610), an autosomal recessive disorder characterized by deficient BCKDH complex activity.
GO:0005759 mitochondrial matrix	NAS PMID:3593587 Purification and characterization of human liver branched-ch...	ACCEPT	Summary: The matrix annotation is consistent with the established mitochondrial BCKDH enzyme. Reason: The accessible source abstract directly reports human liver complex purification and its component activities, but does not itself describe a submitochondrial localization experiment. Retain this NAS assertion with curator deference and independent matrix-model/ortholog support, without rebranding that abstract as a direct matrix assay. Supporting Evidence: Reactome:R-HSA-9859163 PMID:3593587 Human liver BCKADH complex was purified. file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0009083 branched-chain amino acid catabolic process	IDA PMID:3593587 Purification and characterization of human liver branched-ch...	ACCEPT	Summary: The purified human complex oxidizes the ketoacids derived from all three branched-chain amino acids. Reason: The complete abstract of PMID:3593587 measures human liver BCKDH oxidation of KIV, KIC and KMV. These are complex-level assays, with E3 supplementation affecting observed activity; they are not isolated E2 kinetics. DBT nevertheless executes the transacylation step of the measured pathway. The full original was not recovered. Supporting Evidence: Reactome:R-HSA-70895 irreversible oxidative decarboxylation by the branched-chain ketoacid dehydrogenase complex PMID:3593587 The BCKADH effectively oxidized all of KIV, KIC, and KMV, yielding apparent Km values in the range of 14-17 microM for those alpha-keto acids.
GO:0160157 branched-chain alpha-ketoacid dehydrogenase complex	IPI PMID:3593587 Purification and characterization of human liver branched-ch...	ACCEPT	Summary: Human complex purification supports DBT membership in BCKDH. Reason: The source reports purified human liver BCKDH with multiple component bands and readily dissociable lipoamide oxidoreductase. The curated component assignment is retained with the abstract-only limit, and independent E2-specific phosphatase-docking and structural studies corroborate the assembled complex. Supporting Evidence: PMID:22291014 PMID:11839747 PMID:3593587 On SDS-polyacrylamide gel electrophoresis, the purified enzyme complex gave three major bands having molecular weights of 51,000, 46,000, and 36,000 file:human/DBT/DBT-uniprot.txt It is organized around E2, a 24-meric cubic core composed of DBT
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: The immunofluorescence-based mitochondrial assertion is accepted; the matrix sub-compartment is recorded separately. Reason: The original GO_REF:0000052 human localization annotation is preserved; its source image was not independently re-scored. Independent MitoCoP detection and established matrix BCKDH localization agree with it. Verified ancestry makes this organelle-level term redundant with the existing accepted GO:0005759 assertions, not false. Under the root-organelle policy the mitochondrion term is informative in its own right and is kept beside the matrix rows rather than marked too general. Supporting Evidence: GO_REF:0000052 PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix	ISS GO_REF:0000024	ACCEPT	Summary: The ortholog-supported matrix location is consistent with human DBT. Reason: The literal donor P11181 is bovine DBT (Bos taurus), not rat. Its complete current record has an exact matrix IDA assertion. The conserved mitochondrial enzyme architecture, curated human processing and direct human complex evidence support the transfer. Donor provenance was inspected; its original localization paper was not independently reread. Supporting Evidence: GO_REF:0000024 PMID:3593587 file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0043754 dihydrolipoamide branched chain acyltransferase activity	ISS GO_REF:0000024	ACCEPT	Summary: The bovine ortholog supports the conserved DBT transacylase function. Reason: P11181 is bovine DBT and has a current exact-term IDA assertion. The historical duplicate raw rows collapse to this unchanged source object. Human E2 structure and complex chemistry support conservation of the same transacylation activity, without misidentifying the donor as rat. Supporting Evidence: GO_REF:0000024 PMID:3593587 PMID:11839747 file:human/DBT/DBT-uniprot.txt Within this complex, the catalytic function of this enzyme is to accept, and to transfer to coenzyme A, acyl groups that are generated by the branched-chain alpha-keto acid decarboxylase component. file:human/DBT/DBT-uniprot.txt DR InterPro; IPR001078; 2-oxoacid_DH_actylTfrase.
GO:0120552 branched-chain alpha-keto acid decarboxylation to branched-chain acyl-CoA	IDA PMID:3593587 Purification and characterization of human liver branched-ch...	ACCEPT	Summary: DBT performs the E2 step of the experimentally measured human BCKDH conversion. Reason: The original human liver assay demonstrates the complete conversion through NADH production and requires CoA. GO:0120552 explicitly includes three component reactions; DBT performs transfer to CoA within that sequence. This does not assign the E1 decarboxylase or E3 NAD-dependent oxidation activity to DBT. The full source remains unavailable. Supporting Evidence: PMID:3593587 NAD and CoASH were absolutely required for the reaction. PMID:3593587 The BCKADH effectively oxidized all of KIV, KIC, and KMV, yielding apparent Km values in the range of 14-17 microM for those alpha-keto acids.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: MitoCoP directly supports human mitochondrial DBT; the matrix sub-compartment is recorded separately. Reason: The original Table S1 protein group 3886 identifies P11182/DBT (sheet A row 292; sheet B row 265), with subtractive Class 1, spatial Cluster 1 and importomics Class 1. Its operational membrane-association classification is Peripheral, not evidence of a freely soluble enzyme or a particular membrane face. The imported matrix GO column is not a new matrix experiment. Preserve the positive mitochondrial observation while preferring the independently supported existing matrix location. Under the root-organelle policy the mitochondrion term is informative in its own right and is kept beside the matrix rows rather than marked too general. Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP). file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups	TAS Reactome:R-HSA-9865115	TOO GENERAL	Summary: The Reactome acyltransferase role is represented more precisely by existing GO:0043754. Reason: This source explicitly models DBT loss-of-function variants and a defective reaction; its catalyst object points to a mutant BCKDH complex. It is not positive catalytic evidence for every listed mutant. The gene-level acyltransferase chemistry is independently established and its existing accepted GO:0043754 is a verified descendant of the broad source term. Preserve the original TAS source and disease context rather than claiming the modeled variants all retain activity. Supporting Evidence: PMID:3593587 Reactome:R-HSA-9865115 Loss-of-function alleles of DBT are associated with classic, intermittent and thiamine-responsive forms of MSUD Reactome:R-HSA-9859163 transfers the isovaleryl, alpha-methylbutyryl, or isobutyryl groups bound to one of its N6-dihydrolipoyllysine residues onto the substrate CoA
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9865115	ACCEPT	Summary: The modeled DBT-containing entity is located in the mitochondrial matrix. Reason: The actual Reactome graph resolves P11182 through a BCKDH complex containing DBT loss-of-function variants, with compartment 5460 (GO:0005759). This supports the compartment assertion. It does not make DBT the kinase, phosphatase, lipoyltransferase, protease or E3 oxidoreductase in that event, and disease-context location does not imply normal catalytic activity of a mutant. The matrix assignment is consistent with independent DBT evidence. Supporting Evidence: Reactome:R-HSA-9865115 Loss-of-function alleles of DBT are associated with classic, intermittent and thiamine-responsive forms of MSUD file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9859148	ACCEPT	Summary: The modeled DBT-containing entity is located in the mitochondrial matrix. Reason: The actual Reactome graph resolves P11182 through the E1 reaction that loads the DBT lipoyl arm, with compartment 5460 (GO:0005759). This supports the compartment assertion. It does not make DBT the kinase, phosphatase, lipoyltransferase, protease or E3 oxidoreductase in that event. The matrix assignment is consistent with independent DBT evidence. Supporting Evidence: Reactome:R-HSA-9859148 transferring the resulting isovaleryl, alpha-methylbutyryl, or isobutyryl groups onto the lipoyl moiety of the E2 component (DBT) file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9859163	ACCEPT	Summary: The modeled DBT-containing entity is located in the mitochondrial matrix. Reason: The actual Reactome graph resolves P11182 through the DBT transacylation reaction, with compartment 5460 (GO:0005759). This supports the compartment assertion. It does not make DBT the kinase, phosphatase, lipoyltransferase, protease or E3 oxidoreductase in that event. The matrix assignment is consistent with independent DBT evidence. Supporting Evidence: Reactome:R-HSA-9859163 transfers the isovaleryl, alpha-methylbutyryl, or isobutyryl groups bound to one of its N6-dihydrolipoyllysine residues onto the substrate CoA file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9859172	ACCEPT	Summary: The modeled DBT-containing entity is located in the mitochondrial matrix. Reason: The actual Reactome graph resolves P11182 through the DLD reaction that reoxidizes the DBT lipoyl group, with compartment 5460 (GO:0005759). This supports the compartment assertion. It does not make DBT the kinase, phosphatase, lipoyltransferase, protease or E3 oxidoreductase in that event. The matrix assignment is consistent with independent DBT evidence. Supporting Evidence: Reactome:R-HSA-9859172 Dihydrolipoyl dehydrogenase (DLD), the E3 component of the branched-chain alpha-keto acid dehydrogenase complex (BCKDH) file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9907572	ACCEPT	Summary: The modeled DBT-containing entity is located in the mitochondrial matrix. Reason: The actual Reactome graph resolves P11182 through a DLD-deficient reaction with DBT as the lipoyl substrate, with compartment 5460 (GO:0005759). This supports the compartment assertion. It does not make DBT the kinase, phosphatase, lipoyltransferase, protease or E3 oxidoreductase in that event, and disease-context location does not imply normal catalytic activity of a mutant. The matrix assignment is consistent with independent DBT evidence. Supporting Evidence: Reactome:R-HSA-9907572 Loss-of-function mutations in DLD are associated with Maple Syrup Urine Disease 3 file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups	TAS Reactome:R-HSA-9859163	TOO GENERAL	Summary: The Reactome acyltransferase role is represented more precisely by existing GO:0043754. Reason: The normal reaction explicitly transfers isovaleryl, alpha-methylbutyryl or isobutyryl groups from lipoylated DBT to CoA. The gene-level acyltransferase chemistry is independently established and its existing accepted GO:0043754 is a verified descendant of the broad source term. The source describes the normal reaction; no defective-variant inference is needed for this refinement. Supporting Evidence: PMID:3593587 Reactome:R-HSA-9859163 transfers the isovaleryl, alpha-methylbutyryl, or isobutyryl groups bound to one of its N6-dihydrolipoyllysine residues onto the substrate CoA
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-5693148	ACCEPT	Summary: The modeled DBT-containing entity is located in the mitochondrial matrix. Reason: The actual Reactome graph resolves P11182 through BCKDK-mediated regulation of the matrix BCKDH complex, with compartment 5460 (GO:0005759). This supports the compartment assertion. It does not make DBT the kinase, phosphatase, lipoyltransferase, protease or E3 oxidoreductase in that event. The matrix assignment is consistent with independent DBT evidence. Supporting Evidence: Reactome:R-HSA-5693148 catalyses the phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-5693153	ACCEPT	Summary: The modeled DBT-containing entity is located in the mitochondrial matrix. Reason: The actual Reactome graph resolves P11182 through PPM1K-mediated regulation of the matrix BCKDH complex, with compartment 5460 (GO:0005759). This supports the compartment assertion. It does not make DBT the kinase, phosphatase, lipoyltransferase, protease or E3 oxidoreductase in that event. The matrix assignment is consistent with independent DBT evidence. Supporting Evidence: Reactome:R-HSA-5693153 The branched-chain alpha-ketoacid dehydrogenase file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6792572	ACCEPT	Summary: The modeled DBT-containing entity is located in the mitochondrial matrix. Reason: The actual Reactome graph resolves P11182 through LIPT1-mediated lipoyl transfer to DBT, with compartment 5460 (GO:0005759). This supports the compartment assertion. It does not make DBT the kinase, phosphatase, lipoyltransferase, protease or E3 oxidoreductase in that event. The matrix assignment is consistent with independent DBT evidence. Supporting Evidence: Reactome:R-HSA-6792572 Mitochondrial lipoyltransferase 1 (LIPT1) catalyses the transfer of a lipoyl group file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9865121	ACCEPT	Summary: The modeled DBT-containing entity is located in the mitochondrial matrix. Reason: The actual Reactome graph resolves P11182 through a complex with E1 loss-of-function variants, with compartment 5460 (GO:0005759). This supports the compartment assertion. It does not make DBT the kinase, phosphatase, lipoyltransferase, protease or E3 oxidoreductase in that event, and disease-context location does not imply normal catalytic activity of a mutant. The matrix assignment is consistent with independent DBT evidence. Supporting Evidence: Reactome:R-HSA-9865121 Mutations of residues in BCKDHA that participate in subunit associations or that form part of the hydrophobic core destabilize the overall assembly of BCKDH file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9912480	ACCEPT	Summary: The modeled DBT-containing entity is located in the mitochondrial matrix. Reason: The actual Reactome graph resolves P11182 through a complex regulated by BCKDK loss-of-function variants, with compartment 5460 (GO:0005759). This supports the compartment assertion. It does not make DBT the kinase, phosphatase, lipoyltransferase, protease or E3 oxidoreductase in that event, and disease-context location does not imply normal catalytic activity of a mutant. The matrix assignment is consistent with independent DBT evidence. Supporting Evidence: Reactome:R-HSA-9912480 Mutations in branched-chain ketoacid dehydrogenase kinase file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9912527	ACCEPT	Summary: The modeled DBT-containing entity is located in the mitochondrial matrix. Reason: The actual Reactome graph resolves P11182 through a complex regulated by the PPM1K frameshift variant, with compartment 5460 (GO:0005759). This supports the compartment assertion. It does not make DBT the kinase, phosphatase, lipoyltransferase, protease or E3 oxidoreductase in that event, and disease-context location does not imply normal catalytic activity of a mutant. The matrix assignment is consistent with independent DBT evidence. Supporting Evidence: Reactome:R-HSA-9912527 A mild variant of Maple Syrup Urine disease has been identified in patient with a frameshift mutation in the BCKDH phosphatase PPM1K file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005515 protein binding	IPI PMID:22291014 Structural and biochemical characterization of human mitocho...	MODIFY	Summary: DBT directly docks the regulatory phosphatase PPM1K. Reason: The actual human phosphatase study maps binding to the E2b lipoyl-domain C-terminal linker using recombinant proteins and binding-defective linker substitutions. This supports phosphatase binding, GO:0019903, rather than an unspecified protein association. PPM1K performs dephosphorylation; DBT provides its docking surface. The current interaction query did not independently return this pair, so the primary assays are the supporting evidence. Proposed replacements: protein phosphatase binding Supporting Evidence: PMID:22291014 Acidic residues in the C-terminal linker of the E2b lipoyl domain are essential for the interaction between BDP and E2b. PMID:22291014 binding of BDP to the 24-meric transacylase (dihydrolipoyl transacylase; E2b) core of BCKDC results in a 3-fold increase in the dephosphorylation rate of p-E1b.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838081	ACCEPT	Summary: The modeled DBT-containing entity is located in the mitochondrial matrix. Reason: The actual Reactome graph resolves P11182 through the LONP1 mitochondrial substrate collection, with compartment 5460 (GO:0005759). This supports the compartment assertion. It does not make DBT the kinase, phosphatase, lipoyltransferase, protease or E3 oxidoreductase in that event. The matrix assignment is consistent with independent DBT evidence. Supporting Evidence: Reactome:R-HSA-9838081 LONP1 degrades several mitochondrial matrix proteins file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838093	ACCEPT	Summary: The modeled DBT-containing entity is located in the mitochondrial matrix. Reason: The actual Reactome graph resolves P11182 through the LONP1 mitochondrial substrate-binding collection, with compartment 5460 (GO:0005759). This supports the compartment assertion. It does not make DBT the kinase, phosphatase, lipoyltransferase, protease or E3 oxidoreductase in that event. The matrix assignment is consistent with independent DBT evidence. Supporting Evidence: Reactome:R-HSA-9838093 LONP1 binds substrate proteins and degrades them using an ATP-dependent mechanism file:human/DBT/DBT-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0031625 ubiquitin protein ligase binding	IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in...	KEEP AS NON CORE	Summary: DBT association with Parkin is retained as a contextual ubiquitin-ligase-binding observation. Reason: The complete abstract explicitly lists DBT among fourteen potential Parkin interactants from tandem-affinity purification/MS in HEK293 cells. Those fourteen are not all described as mitochondrial proteins. The full original and target-specific controls remain inaccessible, so retention defers to the positive curated IPI and target-positive abstract. It does not establish direct contact, native stoichiometry, DBT ubiquitination or regulation of Parkin. Supporting Evidence: PMID:19725078 Tandem affinity purification/MS revealed 14 potential interactants of Parkin; CKB, DBT, HSPD1, HSPA9, LRPPRC, NDUFS2, PRDX6, SLC25A5, TPI1, UCHL1, UQCRC1, VCL, YWHAZ, YWHAE.
GO:0042645 mitochondrial nucleoid	IDA PMID:18063578 The layered structure of human mitochondrial DNA nucleoids.	KEEP AS NON CORE	Summary: DBT is detected in the cross-linked mitochondrial nucleoid protein set. Reason: The actual original Table 1 lists BCKD E2/DBT/NP_001909 in Class I, with native peptide counts 0/3 and cross-linked counts 12/2. This contradicts the inherited claim that DBT was merely a native-preparation contaminant absent from cross-linked nucleoids. Retain the contextual localization while distinguishing cross-linked association from direct DNA contact or a demonstrated role in nucleoid maintenance. Supporting Evidence: PMID:18063578 A set of core nucleoid proteins is found in both native and cross-linked nucleoids

Gene Description

Functional Isoforms

Existing Annotations Review

Core Functions

Transfers isovaleryl, 2-methylbutyryl and isobutyryl groups from its lipoyl arm to coenzyme A in mitochondrial branched-chain ketoacid oxidation. The E2 oligomer organizes the complex and its mobile lipoyl domain channels intermediates between component active sites.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

📚 Additional Documentation

Notes

Primary Source Notes

📄 View Raw YAML