DBT

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically-inferred mitochondrial localization. DBT is a mitochondrial matrix protein, so this is correct but less specific than the mitochondrial matrix annotations. Reason: DBT is imported into and functions within mitochondria; UniProt records subcellular location as mitochondrion matrix. This IBA is correct though broader than the mitochondrial matrix (GO:0005759) annotations that better capture the precise location. Supporting Evidence: PMID:22291014 The Ca(2+)-independent 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:0043754 dihydrolipoamide branched chain acyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function. DBT is the E2 dihydrolipoyllysine-residue (2-methylpropanoyl)transferase (EC 2.3.1.168) that transfers the branched-chain acyl group from the E1-generated intermediate to CoA. This is the defining catalytic activity of DBT and is well supported by biochemistry and phylogeny. Reason: This is the primary, defining molecular function of DBT as the E2 transacylase of the BCKDH complex. UniProt annotates EC 2.3.1.168 with three branched-chain acyl-CoA-forming reactions, and the phylogenetic inference is consistent with the conserved 2-oxoacid dehydrogenase E2 role. Supporting Evidence: PMID:3593587 NAD and CoASH were absolutely required for the reaction.
GO:0160157 branched-chain alpha-ketoacid dehydrogenase complex	IBA GO_REF:0000033	ACCEPT	Summary: Core cellular component. DBT is the E2 subunit and forms the 24-meric structural core of the BCKDH complex, to which E1 and E3 attach. Reason: DBT is an obligate structural component of the branched-chain alpha-ketoacid dehydrogenase complex (ComplexPortal CPX-2216). The 24-mer E2 core is the scaffold of the whole complex. Supporting Evidence: PMID:22291014 the 24-meric transacylase (dihydrolipoyl transacylase; E2b) core of BCKDC
GO:0005759 mitochondrial matrix	IEA GO_REF:0000120	ACCEPT	Summary: Correct core localization. The assembled BCKDH complex, including the DBT/E2 core, resides in the mitochondrial matrix. Reason: UniProt subcellular location is mitochondrion matrix; the mature protein carries an N-terminal mitochondrial transit peptide (residues 1-61) that is cleaved on matrix import. Electronic inference is consistent with experimental and orthology evidence.
GO:0016746 acyltransferase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Broad parent term for the acyltransferase activity of DBT, from InterPro2GO mapping of the 2-oxoacid dehydrogenase acyltransferase domains. Reason: Not incorrect, but this is a high-level parent of the specific and better molecular function GO:0043754 (dihydrolipoamide branched chain acyltransferase activity). The specific term is already annotated (IBA/IEA/ISS), so this general term adds little and is subsumed. Proposed replacements: dihydrolipoamide branched chain acyltransferase activity
GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Broad parent term for DBT's acyltransferase activity from an ARBA machine-learning rule. Reason: Correct but a general parent of the specific GO:0043754 activity that is already annotated. Retained as accurate but non-informative relative to the specific transacylase term. Proposed replacements: dihydrolipoamide branched chain acyltransferase activity
GO:0043754 dihydrolipoamide branched chain acyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Core molecular function (duplicate of the IBA/ISS annotations), here supported by RHEA/EC electronic mapping (RHEA:18865, EC:2.3.1.168) and orthology. Reason: Correct defining activity supported by the RHEA reactions and EC 2.3.1.168 mapping in UniProt. Duplicate GO IDs across evidence codes are acceptable. Supporting Evidence: PMID:3593587 NAD and CoASH were absolutely required for the reaction.
GO:0120552 branched-chain alpha-keto acid decarboxylation to branched-chain acyl-CoA	IEA GO_REF:0000117	ACCEPT	Summary: Specific biological process describing the overall BCKDH complex reaction that DBT participates in as the E2 transacylase. Reason: Accurately captures the specific committed step performed by the BCKDH complex (oxidative decarboxylation of branched-chain alpha-keto acids to branched-chain acyl-CoA). DBT contributes the transacylation half-reaction. Also independently annotated by IDA (PMID:3593587).
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from the BioPlex 2.0 high-throughput AP-MS interactome (interactants including COX4I1, GRPEL2, MRRF, CA5B). Uninformative as to molecular function. Reason: This is a large-scale affinity-purification/mass-spectrometry screen generating generic protein binding annotations; the term is uninformative and does not reflect a specific DBT molecular function. Retained (not removed) per curation policy on interactome-derived protein binding. 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...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from the BioPlex 3.0 dual proteome-scale AP-MS interactome. Uninformative as to molecular function. Reason: High-throughput AP-MS interactome data yielding a generic protein binding term with no specific functional content. Retained per policy for interactome-derived protein binding rather than removed. 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...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a multimodal (AP-MS + immunofluorescence) cell-mapping dataset in U2OS cells. Uninformative as to molecular function. Reason: Systematic proteome-scale interaction/co-localization mapping produces a generic protein binding term without specific functional meaning for DBT. Retained per policy rather than removed. 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	KEEP AS NON CORE	Summary: DBT participates in isoleucine catabolism as the E2 subunit acting on the isoleucine-derived branched-chain keto acid (KMV / alpha-keto-beta-methylvalerate). Reason: Correct, but this is one of three amino-acid-specific sub-branches subsumed by the core branched-chain amino acid catabolic process (GO:0009083). DBT is not isoleucine-specific; the BCKDH complex acts on all three BCAA-derived keto acids. Keep as a valid, more granular but non-core annotation.
GO:0006552 L-leucine catabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: DBT participates in leucine catabolism as the E2 subunit acting on the leucine-derived keto acid (KIC / alpha-ketoisocaproate). Reason: Correct but a substrate-specific sub-branch of the core BCAA catabolic process (GO:0009083). DBT/BCKDH is not leucine-specific; keep as granular non-core.
GO:0006574 L-valine catabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: DBT participates in valine catabolism as the E2 subunit acting on the valine-derived keto acid (KIV / alpha-ketoisovalerate). Reason: Correct but a substrate-specific sub-branch of the core BCAA catabolic process (GO:0009083). DBT/BCKDH acts on all three BCAA keto acids; keep as granular non-core.
GO:0009083 branched-chain amino acid catabolic process	IEA GO_REF:0000107	ACCEPT	Summary: Core biological process. As the E2 subunit of the BCKDH complex, DBT is required for the committed oxidative decarboxylation step of leucine, isoleucine, and valine catabolism. Reason: This is the central biological process for DBT and the whole BCKDH complex. Deficiency of DBT (MSUD type II) blocks BCAA catabolism, confirming the requirement. Supporting Evidence: PMID:3593587 The BCKADH effectively oxidized all of KIV, KIC, and KMV
GO:0009083 branched-chain amino acid catabolic process	TAS Reactome:R-HSA-70895	ACCEPT	Summary: Core biological process (Reactome pathway "Branched-chain amino acid catabolism"), duplicate of the IEA/IDA annotations. Reason: Correct core process supported by the Reactome pathway describing BCAA catabolism. Duplicate of the experimentally and electronically supported GO:0009083 annotations.
GO:0005759 mitochondrial matrix	NAS PMID:3593587 Purification and characterization of human liver branched-ch...	ACCEPT	Summary: Mitochondrial matrix localization asserted by ComplexPortal from the purified human liver BCKDH complex study. Reason: Correct core localization. The purified human liver BCKDH complex is a matrix multienzyme complex; UniProt records mitochondrion matrix as the subcellular location. Supporting Evidence: PMID:3593587 Human liver BCKADH complex was purified.
GO:0009083 branched-chain amino acid catabolic process	IDA PMID:3593587 Purification and characterization of human liver branched-ch...	ACCEPT	Summary: Direct experimental demonstration that the purified human liver BCKDH complex (containing the DBT/E2 subunit) oxidizes the branched-chain keto acids derived from all three BCAAs. Reason: Direct assay evidence for the core BCAA catabolic function. The purified complex effectively oxidized KIV, KIC, and KMV, the keto acids of valine, leucine, and isoleucine. Supporting Evidence: 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: Core cellular component. ComplexPortal (CPX-2216) documents DBT/E2 as a component of the purified branched-chain alpha-ketoacid dehydrogenase complex. Reason: DBT is an obligate subunit of the BCKDH complex; the purified human liver complex showed the three enzymatic components including the E2 transacylase (bands at ~51/46/36 kDa plus the readily dissociable E3/lipoamide oxidoreductase). Supporting Evidence: PMID:3593587 On SDS-polyacrylamide gel electrophoresis, the purified enzyme complex gave three major bands
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: Immunofluorescence-based (Human Protein Atlas) mitochondrial localization. Reason: Consistent with the established mitochondrial matrix localization of DBT. Broader than the matrix term but correct.
GO:0005759 mitochondrial matrix	ISS GO_REF:0000024	ACCEPT	Summary: Matrix localization inferred by sequence similarity to the rat ortholog (P11181). Reason: Correct core localization; consistent with UniProt subcellular location (mitochondrion matrix) and orthology to rat DBT.
GO:0043754 dihydrolipoamide branched chain acyltransferase activity	ISS GO_REF:0000024	ACCEPT	Summary: Core molecular function inferred by sequence similarity to the rat ortholog (P11181). Duplicate of the IBA/IEA annotations. Reason: The defining E2 transacylase activity, well supported by orthology to the biochemically characterized rat DBT and by the human EC 2.3.1.168 assignment.
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: Direct experimental support for participation in the overall branched-chain keto acid oxidative decarboxylation reaction, from the purified human liver complex. Reason: The purified complex catalyzed the oxidative decarboxylation of the branched-chain keto acids (requiring NAD and CoASH), the exact process this term describes. Supporting Evidence: PMID:3593587 NAD and CoASH were absolutely required for the reaction.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput mitochondrial proteome localization of DBT in a high-confidence human mitochondrial proteome dataset. Reason: Consistent with the established matrix localization; a broad but correct mitochondrial CC assignment from a high-confidence mitochondrial proteome dataset. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups	TAS Reactome:R-HSA-9865115	MARK AS OVER ANNOTATED	Summary: Broad acyltransferase parent term from Reactome (DBT loss-of-function reaction). Reason: Correct but a general parent of the specific GO:0043754 activity that is already annotated. Non-informative relative to the specific transacylase term. Proposed replacements: dihydrolipoamide branched chain acyltransferase activity
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9865115	ACCEPT	Summary: Reactome-asserted mitochondrial matrix localization. Reason: Correct core localization consistent with UniProt and experimental evidence.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9859148	ACCEPT	Summary: Reactome-asserted mitochondrial matrix localization (BCKDHA:BCKDHB decarboxylation reaction). Reason: Correct core localization; duplicate of the other matrix annotations.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9859163	ACCEPT	Summary: Reactome-asserted mitochondrial matrix localization. Reason: Correct core localization; duplicate of the other matrix annotations.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9859172	ACCEPT	Summary: Reactome-asserted mitochondrial matrix localization (DLD dehydrogenation step). Reason: Correct core localization; duplicate of the other matrix annotations.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9907572	ACCEPT	Summary: Reactome-asserted mitochondrial matrix localization. Reason: Correct core localization; duplicate of the other matrix annotations.
GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups	TAS Reactome:R-HSA-9859163	MARK AS OVER ANNOTATED	Summary: Broad acyltransferase parent term from Reactome. Reason: Correct but a general parent of the specific GO:0043754 activity already annotated. Non-informative relative to the specific transacylase term. Proposed replacements: dihydrolipoamide branched chain acyltransferase activity
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-5693148	ACCEPT	Summary: Reactome-asserted mitochondrial matrix localization. Reason: Correct core localization; duplicate of the other matrix annotations.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-5693153	ACCEPT	Summary: Reactome-asserted mitochondrial matrix localization (PPM1K dephosphorylates p-BCKDH). Reason: Correct core localization; duplicate of the other matrix annotations.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-6792572	ACCEPT	Summary: Reactome-asserted mitochondrial matrix localization. Reason: Correct core localization; duplicate of the other matrix annotations.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9865121	ACCEPT	Summary: Reactome-asserted mitochondrial matrix localization. Reason: Correct core localization; duplicate of the other matrix annotations.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9912480	ACCEPT	Summary: Reactome-asserted mitochondrial matrix localization (BCKDK loss-of-function). Reason: Correct core localization; duplicate of the other matrix annotations.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9912527	ACCEPT	Summary: Reactome-asserted mitochondrial matrix localization (PPM1K variant). Reason: Correct core localization; duplicate of the other matrix annotations.
GO:0005515 protein binding	IPI PMID:22291014 Structural and biochemical characterization of human mitocho...	MARK AS OVER ANNOTATED	Summary: Protein binding annotation from the structural/biochemical characterization of the BCKDH phosphatase (BDP/PPM1K, Q8N3J5). This captures the biologically meaningful interaction between the DBT/E2 core and the regulatory phosphatase, but the GO term itself (bare protein binding) is uninformative. Reason: Although the underlying interaction (PPM1K binding the 24-meric E2b core, with acidic residues in the E2b lipoyl-domain C-terminal linker essential for the interaction) is genuine and functionally important for complex regulation, the annotated term is the generic protein binding term with no molecular-function content. Retained (not removed) per policy; a more informative annotation (e.g. the E2-core scaffolding of the regulatory phosphatase) would be preferable. Supporting Evidence: PMID:22291014 The Ca(2+)-independent 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: Reactome-asserted mitochondrial matrix localization (LONP1 degrades matrix proteins). Reason: Correct core localization; duplicate of the other matrix annotations.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838093	ACCEPT	Summary: Reactome-asserted mitochondrial matrix localization (LONP1 binds matrix proteins). Reason: Correct core localization; duplicate of the other matrix annotations.
GO:0031625 ubiquitin protein ligase binding	IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in...	MARK AS OVER ANNOTATED	Summary: Annotation derived from a Parkin (E3 ubiquitin ligase, O60260) tandem-affinity-purification/MS interactome, in which DBT was one of 14 mitochondrial proteins co-purifying with overexpressed Parkin. Reason: This is a guilt-by-association co-purification from a Parkin overexpression proteomics screen, not a demonstration of a specific, direct DBT-ubiquitin-ligase binding function. DBT is a metabolic matrix enzyme captured among many mitochondrial proteins; the term over-states a functional binding role. Retained (not removed) per policy on interactome-derived binding annotations. 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.	MARK AS OVER ANNOTATED	Summary: DBT was identified among proteins in biochemically purified mitochondrial nucleoid preparations, but this study distinguished a core set of nucleoid proteins that crosslink to mtDNA from peripheral metabolic proteins that do not. Reason: DBT is a soluble matrix metabolic enzyme; its recovery in native nucleoid preparations reflects co-purification/peripheral association rather than a genuine nucleoid localization or a role in mtDNA transactions. The paper explicitly contrasts core nucleoid proteins that crosslink to mtDNA with additional metabolic proteins that do not. Retained (not removed) as it derives from an experimental IDA whose full text is not available, but flagged as an over-annotation of the nucleoid compartment. Supporting Evidence: PMID:18063578 Several other metabolic proteins and chaperones identified in native nucleoids, including ATAD3, were not observed to cross-link to mtDNA.

Gene Description

Existing Annotations Review

Core Functions

E2 subunit dihydrolipoyllysine-residue (2-methylpropanoyl)transferase activity of the BCKDH complex; transfers the branched-chain acyl group from the lipoyl-bound intermediate to coenzyme A during the committed step of branched-chain amino acid catabolism in the mitochondrial matrix.

As the E2 transacylase of the BCKDH complex, DBT participates in the overall oxidative decarboxylation of branched-chain alpha-keto acids to branched-chain acyl-CoA, contributing the CoA-dependent transacylation half-reaction.

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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