BCKDHB

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0009083 branched-chain amino acid catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) propagation of the core biological process. As the E1-beta subunit of the BCKDH complex, BCKDHB is directly required for the committed, rate-limiting oxidative decarboxylation step of BCAA (valine/leucine/isoleucine) catabolism. Reason: Correct and central to the gene's function; well supported by direct experimental evidence in human and orthologs. This is a core biological process for BCKDHB. Supporting Evidence: UniProtKB:P21953 Together with BCKDHA forms the heterotetrameric E1 subunit of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. The BCKD complex catalyzes the multi-step oxidative decarboxylation of alpha-ketoacids derived from the branched-chain amino-acids valine, leucine and isoleucine producing CO2 and acyl-CoA
GO:0160157 branched-chain alpha-ketoacid dehydrogenase complex	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment of the cellular component. BCKDHB is an integral, constitutive subunit of the BCKDH complex, forming (with BCKDHA) the E1 alpha2-beta2 decarboxylase that associates with the E2 (DBT) core and E3 (DLD). Reason: Correct core localization to the multienzyme complex; supported by structural, biochemical and disease genetics evidence (heterotetrameric E1 component). Supporting Evidence: UniProtKB:P21953 Heterotetramer of 2 alpha/BCKDHA and 2 beta chains/BCKDHB that forms the branched-chain alpha-keto acid decarboxylase (E1) component of the BCKD complex
GO:0007584 response to nutrient	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (IBA) annotation reflecting that BCAA catabolic flux through BCKDH is nutritionally regulated. This is a broad, downstream physiological process rather than the molecular role of the beta subunit. It descends from PAINT node PANTHER:PTN000178891 in PTHR42980, where the IBD is seeded by a single rat descendant (RGD:2197) and dates from 2017 - the thinnest of the three IBAs this gene receives. Reason: Not wrong at the pathway level (BCKDH flux responds to nutrient status through BCKDK/PPM1K-mediated phosphorylation of E1-alpha), but this is a peripheral, non-core physiological association for the E1-beta subunit rather than its molecular role, and it rests on one rodent seed. Retained as non-core rather than removed: a whole-animal dietary response is a legitimate, if uninformative, thing for a rate-limiting catabolic enzyme subunit to be annotated to, and there is no evidence contradicting it in human. Supporting Evidence: file:human/BCKDHB/BCKDHB-deep-research-falcon.md BCKDK is upregulated under nutrient-excess conditions and suppressed during nutrient scarcity or catabolic stress
GO:0003863 branched-chain 2-oxo acid dehydrogenase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (IEA) assignment of the E1 decarboxylase molecular function (EC 1.2.4.4), mapped via ortholog, RHEA reactions (RHEA:13457/84639/84643) and EC. This is the core catalytic activity of the BCKDH E1 component. Reason: The mapping is correct and matches the UniProt catalytic activity and the experimental IDA/IMP annotations of the same term. The IEA uses 'enables' whereas the manual annotations use 'contributes_to'; contributes_to is technically more precise for a subunit of a shared active site, but the IEA is not wrong at this level and captures the correct enzymatic function. Supporting Evidence: UniProtKB:P21953 Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 3-methyl-2-oxobutanoate file:human/BCKDHB/BCKDHB-deep-research-falcon.md thiamine diphosphate (ThDP)-dependent decarboxylase
GO:0005759 mitochondrial matrix	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (IEA) assignment of mitochondrial matrix localization via ortholog and UniProt subcellular location keyword. BCKDH is a soluble matrix multienzyme complex. Reason: Correct and consistent with the UniProt subcellular location and with NAS/ISS/TAS annotations of the same term. Supporting Evidence: UniProtKB:P21953 SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005515 protein binding	IPI PMID:12902323 Roles of His291-alpha and His146-beta' in the reductive acyl...	MARK AS OVER ANNOTATED	Summary: IPI 'protein binding' annotation whose WITH/FROM is UniProtKB:P12694 (BCKDHA), i.e. the direct E1-alpha partner with which BCKDHB forms the alpha2-beta2 heterotetramer. This paper dissects the catalytic mechanism (His-alpha/His-beta' in reductive acylation) of the assembled E1. Reason: The interaction is real (BCKDHB obligately binds BCKDHA), but the bare 'protein binding' term is uninformative. The biologically meaningful capture of this interaction is already provided by the E1 heterotetramer / BCKDH complex annotations (GO:0160157) and the E1 decarboxylase molecular function (GO:0003863). Supporting Evidence: UniProtKB:P21953 P21953; P12694: BCKDHA; NbExp=15; IntAct=EBI-1029067, EBI-1029053;
GO:0005515 protein binding	IPI PMID:15166214 Cross-talk between thiamin diphosphate binding and phosphory...	MARK AS OVER ANNOTATED	Summary: IPI 'protein binding' annotation, WITH/FROM UniProtKB:P12694 (BCKDHA). This study addresses ThDP-binding / phosphorylation-loop cross-talk in the assembled E1 decarboxylase, again reflecting the BCKDHB-BCKDHA E1 heterotetramer. Reason: Real interaction but uninformative bare 'protein binding'. The E1 heterotetramer is better captured by the BCKDH complex (GO:0160157) and E1 activity (GO:0003863) annotations. Supporting Evidence: UniProtKB:P21953 P21953; P12694: BCKDHA; NbExp=15; IntAct=EBI-1029067, EBI-1029053;
GO:0005515 protein binding	IPI PMID:15576032 Molecular mechanism for regulation of the human mitochondria...	MARK AS OVER ANNOTATED	Summary: IPI 'protein binding' annotation, WITH/FROM UniProtKB:P12694 (BCKDHA). This paper concerns regulation of the assembled BCKDH complex by phosphorylation of E1-alpha, again reflecting the E1 heterotetramer interaction. Reason: Real interaction but uninformative bare 'protein binding'; the meaningful content is captured by the complex (GO:0160157) and MF (GO:0003863) annotations. Supporting Evidence: UniProtKB:P21953 P21953; P12694: BCKDHA; NbExp=15; IntAct=EBI-1029067, EBI-1029053;
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Large-scale interactome (BioPlex) IPI, WITH/FROM UniProtKB:P12694 (BCKDHA), recovering the BCKDHB-BCKDHA interaction that constitutes the E1 heterotetramer. Reason: High-throughput detection of the genuine E1-alpha/E1-beta interaction, but the generic 'protein binding' term is uninformative and the interaction is already captured by the BCKDH complex annotation (GO:0160157). Supporting Evidence: UniProtKB:P21953 P21953; P12694: BCKDHA; NbExp=15; IntAct=EBI-1029067, EBI-1029053;
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Large-scale interactome (BioPlex 3.0) IPI, WITH/FROM UniProtKB:P12694 (BCKDHA), again capturing the BCKDHB-BCKDHA E1 heterotetramer interaction. Reason: Genuine but uninformative bare 'protein binding'; the meaningful E1-alpha interaction is captured by the BCKDH complex (GO:0160157) and E1 MF (GO:0003863). Supporting Evidence: UniProtKB:P21953 P21953; P12694: BCKDHA; NbExp=15; IntAct=EBI-1029067, EBI-1029053;
GO:0006550 L-isoleucine catabolic process	IEA GO_REF:0000107	ACCEPT	Summary: Electronic (Ensembl Compara ortholog) transfer of a more granular BCAA subprocess. The BCKDH E1 decarboxylates KMV (the isoleucine-derived 2-oxo acid), so this is a correct, more specific descendant of BCAA catabolism. Reason: Biochemically correct - the E1 decarboxylase acts on the isoleucine-derived branched-chain 2-oxo acid (S)-3-methyl-2-oxopentanoate (KMV). More granular than, and consistent with, the core GO:0009083 annotation; retain as non-core detail. Supporting Evidence: UniProtKB:P21953 Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + (S)-3-methyl-2- PMID:3593587 The BCKADH effectively oxidized all of KIV, KIC, and KMV
GO:0006552 L-leucine catabolic process	IEA GO_REF:0000107	ACCEPT	Summary: Electronic (Ensembl Compara ortholog) transfer. The BCKDH E1 decarboxylates KIC (4-methyl-2-oxopentanoate), the leucine-derived 2-oxo acid, so this granular BCAA subprocess is correct. Reason: Biochemically correct (E1 acts on the leucine-derived branched-chain 2-oxo acid, 4-methyl-2-oxopentanoate/KIC). More specific than, and consistent with, the core GO:0009083 annotation; retain as non-core detail. Supporting Evidence: UniProtKB:P21953 Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 4-methyl-2-oxopentanoate PMID:3593587 The BCKADH effectively oxidized all of KIV, KIC, and KMV
GO:0006574 L-valine catabolic process	IEA GO_REF:0000107	ACCEPT	Summary: Electronic (Ensembl Compara ortholog) transfer. The BCKDH E1 decarboxylates KIV (3-methyl-2-oxobutanoate), the valine-derived 2-oxo acid, so this granular BCAA subprocess is correct. Reason: Biochemically correct (E1 acts on the valine-derived branched-chain 2-oxo acid, 3-methyl-2-oxobutanoate/KIV; RHEA:13457 is the experimentally verified human reaction). More specific than, and consistent with, the core GO:0009083 annotation; retain as non-core detail. Supporting Evidence: UniProtKB:P21953 Reaction=N(6)-[(R)-lipoyl]-L-lysyl-[protein] + 3-methyl-2-oxobutanoate PMID:3593587 The BCKADH effectively oxidized all of KIV, KIC, and KMV
GO:0032991 protein-containing complex	IEA GO_REF:0000107	MODIFY	Summary: Electronic (Ensembl Compara ortholog) transfer of the generic 'protein-containing complex' term. BCKDHB is a subunit of the specific, well-defined BCKDH complex. Reason: Correct but far too general: BCKDHB is part of the specific branched-chain alpha-ketoacid dehydrogenase complex, which is already directly annotated (GO:0160157) with stronger evidence. Replace the generic term with the specific one. Proposed replacements: branched-chain alpha-ketoacid dehydrogenase complex Supporting Evidence: UniProtKB:P21953 Heterotetramer of 2 alpha/BCKDHA and 2 beta chains/BCKDHB that forms the branched-chain alpha-keto acid decarboxylase (E1) component of the BCKD complex
GO:0005759 mitochondrial matrix	NAS PMID:3593587 Purification and characterization of human liver branched-ch...	ACCEPT	Summary: Non-traceable author statement (ComplexPortal-assigned) of matrix localization, supported by purification of the intact human liver BCKDH complex, a soluble matrix multienzyme complex. Reason: Consistent with all other matrix annotations and with UniProt subcellular location. Correct core localization. Supporting Evidence: PMID:3593587 Purification and characterization of human liver branched-chain alpha-keto acid dehydrogenase complex.
GO:0009083 branched-chain amino acid catabolic process	IDA PMID:3593587 Purification and characterization of human liver branched-ch...	ACCEPT	Summary: Direct experimental (IDA) annotation of the core BCAA catabolic process. The purified human liver BCKDH complex oxidized all three branched-chain 2-oxo acids (KIV, KIC, KMV), demonstrating its role in BCAA (valine/leucine/isoleucine) catabolism. Reason: Direct biochemical evidence for the complex's role in BCAA catabolism; this is a core process for BCKDHB. 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: ComplexPortal (CPX-2216) IPI annotation of BCKDHB as a subunit of the BCKDH complex, based on co-purification of the intact human liver complex. Reason: Correct core complex membership, supported by biochemical purification showing the subunit composition of the human liver BCKDH complex. Supporting Evidence: PMID:3593587 the purified enzyme complex gave three major bands having molecular weights of 51,000, 46,000, and 36,000
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: Human Protein Atlas immunofluorescence (IDA) localization of BCKDHB to mitochondria. Less granular than the matrix annotations but consistent. Reason: Correct localization; mitochondrion is a valid parent of the more specific mitochondrial matrix localization also annotated. Directly supported by immunofluorescence.
GO:0005759 mitochondrial matrix	NAS PMID:10745006 Crystal structure of human branched-chain alpha-ketoacid deh...	ACCEPT	Summary: Author statement (NAS, UniProt) of mitochondrial matrix localization, associated with the crystal structure paper of the human E1b heterotetramer. Reason: Consistent with the UniProt subcellular location and all other matrix annotations; correct core localization. Supporting Evidence: UniProtKB:P21953 SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0005759 mitochondrial matrix	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity (ISS) transfer from ortholog (UniProtKB:P21839, rat E1-beta) asserting BCKDHB is active in the mitochondrial matrix, where the BCKDH complex functions. Reason: Correct: the E1 decarboxylase acts within the mitochondrial matrix as part of the BCKDH complex. The 'is_active_in' qualifier appropriately links localization to the site of catalytic function. Supporting Evidence: UniProtKB:P21953 SUBCELLULAR LOCATION: Mitochondrion matrix
GO:0120552 branched-chain alpha-keto acid decarboxylation to branched-chain acyl-CoA	IMP PMID:10745006 Crystal structure of human branched-chain alpha-ketoacid deh...	ACCEPT	Summary: Mutant-phenotype (IMP) annotation to the specific process of branched-chain alpha-keto acid decarboxylation. The crystal structure of human E1b rationalizes how MSUD mutations in the beta subunit impair this decarboxylation step. Reason: Accurate, appropriately specific description of the E1 decarboxylase step in which BCKDHB participates. Supported by structural/mutational analysis of MSUD variants. Supporting Evidence: PMID:10745006 The known MSUD mutations affect the functioning of E1b by interfering with the cofactor and K(+) sites, the packing of hydrophobic cores, and the precise arrangement of residues at or near several subunit interfaces.
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 (IDA) annotation to the branched-chain alpha-keto acid decarboxylation process, supported by the purified human liver BCKDH complex oxidizing all three branched-chain 2-oxo acids. Reason: Correct, appropriately specific process describing the reaction the E1 component (including BCKDHB) initiates. Directly supported by biochemical characterization. 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:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9865121	ACCEPT	Summary: Reactome (TAS) matrix localization annotation from a curated pathway reaction involving the BCKDH complex. Reason: Consistent with the UniProt subcellular location and the other matrix annotations; correct core localization from a curated pathway source.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput (HTP) mitochondrial proteomics localization of BCKDHB to mitochondria (Morgenstern et al. high-confidence human mitochondrial proteome). Reason: Consistent with all other localization evidence; a valid (if less specific) parent of the mitochondrial matrix localization. Correct. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
GO:0160157 branched-chain alpha-ketoacid dehydrogenase complex	IMP PMID:2022752 Maple syrup urine disease. Complete defect of the E1 beta su...	ACCEPT	Summary: Mutant-phenotype (IMP) evidence that BCKDHB is part of the BCKDH complex: an 11-bp deletion abolishing the beta subunit destabilizes E1-alpha and reduces complex activity to ~6% of normal, demonstrating BCKDHB is a required structural subunit. Reason: Strong genetic/biochemical evidence that BCKDHB is an integral subunit of the BCKDH complex whose absence disassembles/inactivates the enzyme. Core complex membership. Supporting Evidence: PMID:2022752 The absence of the E1 beta subunit results in instability of the E1 alpha subunit.
GO:0160157 branched-chain alpha-ketoacid dehydrogenase complex	IDA PMID:9582350 Impaired assembly of E1 decarboxylase of the branched-chain ...	ACCEPT	Summary: Direct experimental (IDA) evidence that BCKDHB is a subunit of the E1 component: reconstitution/assembly studies show wild-type E1 exists as alpha2-beta2 tetramers of E1-alpha and E1-beta. Reason: Directly demonstrates BCKDHB as part of the E1 decarboxylase of the BCKDH complex (alpha2-beta2 tetramer). Core complex membership. Supporting Evidence: PMID:9582350 The E1 decarboxylase component of the human branched-chain ketoacid dehydrogenase complex comprises two E1alpha (45.5 kDa) and two E1beta (37.5 kDa) subunits forming an alpha2 beta2 tetramer.
GO:0160157 branched-chain alpha-ketoacid dehydrogenase complex	IDA PMID:10745006 Crystal structure of human branched-chain alpha-ketoacid deh...	ACCEPT	Summary: Direct experimental (IDA) evidence from the crystal structure of the human E1b component (170 kDa alpha2-beta2 heterotetramer), establishing BCKDHB as an integral subunit of the BCKDH complex. Reason: Structural determination of the E1b heterotetramer directly demonstrates BCKDHB as part of the complex. Core complex membership. Supporting Evidence: PMID:10745006 the 170 kDa alpha(2)beta(2) heterotetrameric E1b component of the branched-chain alpha-ketoacid dehydrogenase multienzyme complex.
GO:0003863 branched-chain 2-oxo acid dehydrogenase activity	IDA PMID:10745006 Crystal structure of human branched-chain alpha-ketoacid deh...	ACCEPT	Summary: Direct experimental (IDA) annotation with the appropriate 'contributes_to' qualifier: BCKDHB contributes to the E1 decarboxylase molecular function. The crystal structure shows the active site at the alpha-beta' interface, with beta subunit residues involved in cofactor and K+ binding. Reason: Core molecular function. 'contributes_to' correctly reflects that catalysis requires both subunits (active site at alpha-beta' interface); BCKDHB alone does not carry the full activity but is essential to it. Supporting Evidence: PMID:10745006 The position of two important potassium (K(+)) ions was determined. UniProtKB:P21953 The E1 subunit catalyzes the first step with the decarboxylation of the alpha-ketoacid
GO:0003863 branched-chain 2-oxo acid dehydrogenase activity	IDA PMID:9582350 Impaired assembly of E1 decarboxylase of the branched-chain ...	ACCEPT	Summary: Direct experimental (IDA) annotation of the E1 decarboxylase activity with 'contributes_to'. E1-alpha missense mutations abolish E1 and BCKDH catalytic activity, and BCKDHB is a required subunit of the catalytically competent alpha2-beta2 E1. Reason: Core molecular function; 'contributes_to' is correct for a shared active site formed by the alpha2-beta2 heterotetramer. Supporting Evidence: PMID:9582350 the E1alpha subunit is affected, resulting in the loss of E1 and branched-chain ketoacid dehydrogenase catalytic activities.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-5693148	ACCEPT	Summary: Reactome (TAS) mitochondrial matrix localization from a curated pathway reaction involving the BCKDH complex. Reason: Consistent with all other matrix localization evidence; correct core localization.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-5693153	ACCEPT	Summary: Reactome (TAS) mitochondrial matrix localization from a curated pathway reaction involving the BCKDH complex. Reason: Consistent with all other matrix localization evidence; correct core localization.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9912527	ACCEPT	Summary: Reactome (TAS) mitochondrial matrix localization from a curated pathway reaction (BCKDH dephosphorylation by PPM1K) involving the BCKDH complex. Reason: Consistent with all other matrix localization evidence; correct core localization.
GO:0003863 branched-chain 2-oxo acid dehydrogenase activity	IMP PMID:2022752 Maple syrup urine disease. Complete defect of the E1 beta su...	ACCEPT	Summary: Mutant-phenotype (IMP) evidence for the E1 decarboxylase activity: loss of the beta subunit reduces BCKDH activity to ~6% of normal, demonstrating BCKDHB is required for the complex's dehydrogenase activity. Annotated with 'contributes_to'. Reason: Core molecular function supported by loss-of-function genetics; 'contributes_to' is appropriate for a subunit of the shared active site. Supporting Evidence: PMID:2022752 The BCKDH activity in the proband with MSUD was approximately 6% of the normal control level.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9859148	ACCEPT	Summary: Reactome (TAS) mitochondrial matrix localization from the curated reaction in which the BCKDHA:BCKDHB E1 tetramer decarboxylates KIC, KMV and KIV. Reason: Consistent with all other matrix localization evidence and directly describes the E1 catalytic reaction. Correct core localization.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9859163	ACCEPT	Summary: Reactome (TAS) mitochondrial matrix localization from a curated pathway reaction involving the BCKDH complex. Reason: Consistent with all other matrix localization evidence; correct core localization.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9859172	ACCEPT	Summary: Reactome (TAS) mitochondrial matrix localization from the curated reaction in which the DLD (E3) dimer dehydrogenates dihydrolipoyl, part of the BCKDH complex cycle. Reason: Consistent with all other matrix localization evidence; correct core localization.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9865115	ACCEPT	Summary: Reactome (TAS) mitochondrial matrix localization from a curated reaction involving DBT (E2) loss-of-function within the BCKDH pathway. Reason: Consistent with all other matrix localization evidence; correct core localization.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9907572	ACCEPT	Summary: Reactome (TAS) mitochondrial matrix localization from a curated pathway reaction involving the BCKDH complex. Reason: Consistent with all other matrix localization evidence; correct core localization.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9912480	ACCEPT	Summary: Reactome (TAS) mitochondrial matrix localization from the curated reaction in which BCKDK loss-of-function mutations fail to phosphorylate BCKDH. Reason: Consistent with all other matrix localization evidence; correct core localization.
GO:0005739 mitochondrion	IMP PMID:2022752 Maple syrup urine disease. Complete defect of the E1 beta su...	ACCEPT	Summary: Mutant-phenotype (IMP) mitochondrial localization inference. The disease allele deletes part of the E1-beta mitochondrial targeting leader peptide, consistent with normal mitochondrial localization of the wild-type protein. Reason: Correct localization; a valid parent of the mitochondrial matrix annotations. The mutation disrupts the mitochondrial targeting peptide, underscoring the protein's mitochondrial destination. Supporting Evidence: PMID:2022752 An 11-bp deletion was identified in the region that encoded the mitochondrial targeting leader peptide in the E1 beta cDNA.
GO:0009083 branched-chain amino acid catabolic process	IMP PMID:2022752 Maple syrup urine disease. Complete defect of the E1 beta su...	ACCEPT	Summary: Mutant-phenotype (IMP) evidence for the core BCAA catabolic process: complete loss of the beta subunit causes MSUD (BCAA/BCKA accumulation) and reduces BCKDH activity to ~6% of normal, demonstrating BCKDHB's requirement for BCAA catabolism. Reason: Strong loss-of-function evidence for a core biological process; MSUD 1B is the pathological consequence of impaired BCAA catabolism due to E1-beta deficiency. Supporting Evidence: PMID:2022752 These observations show the biological importance of the E1 beta subunit of BCKDH to maintain normal function of the enzyme activity.
GO:0030976 thiamine pyrophosphate binding	IDA PMID:10745006 Crystal structure of human branched-chain alpha-ketoacid deh...	NEW	Summary: Not present in the seeded GOA, but directly supported. The E1 active site lies at the alpha/beta' interface and the thiamine diphosphate cofactor is shared between the two subunits: UniProt records a ThDP BINDING site at position 152 of P21953 annotated "ligand shared with alpha subunit" with ECO:0000269\|PubMed:10745006, and the crystal structure of human E1b resolves the bound cofactor. Added as a NEW subunit-specific molecular function. Reason: Cofactor binding is the concrete, subunit-level molecular function BCKDHB brings to the shared E1 active site (the beta subunit contributes the thiazolium-ring contacts, the alpha subunit the diphosphate/Mg2+ contacts). It is documented crystallographically and by a UniProt BINDING feature with experimental evidence, but is absent from the current GOA for this gene. Supporting Evidence: PMID:10745006 One of these ions assists a loop that is close to the cofactor to adopt the proper conformation. file:human/BCKDHB/BCKDHB-deep-research-falcon.md thiamine diphosphate (ThDP)-dependent decarboxylase
GO:0030955 potassium ion binding	IDA PMID:10745006 Crystal structure of human branched-chain alpha-ketoacid deh...	NEW	Summary: Not present in the seeded GOA. The crystal structure of human E1b located two structural K+ ions, the second of them in the beta subunit near its interface with the C-terminal domain of the alpha subunit; UniProt correspondingly records six structural K(+) BINDING sites on BCKDHB (positions 178, 180, 181, 228, 231 and 233 of P21953) with ECO:0000269\|PubMed:10745006. Added as a NEW, non-core molecular function. Reason: Experimentally located structural cation sites on this subunit, which the same study implicates in the mechanism by which MSUD mutations impair E1b. Structural rather than catalytic, so recorded as supporting detail and not as a core function. Supporting Evidence: PMID:10745006 The position of two important potassium (K(+)) ions was determined. PMID:10745006 The second is located in the beta subunit near the interface with the small C-terminal domain of the alpha subunit.

Gene Description

Existing Annotations Review

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References

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