PDHB

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006086 pyruvate decarboxylation to acetyl-CoA	IBA GO_REF:0000033	ACCEPT	Summary: PDHB, as the E1beta subunit of the PDC, participates in the oxidative decarboxylation of pyruvate to acetyl-CoA. This phylogenetically-inferred BP annotation is well supported by orthology, structural biology, and disease evidence, and represents a core biological process for the gene. Reason: Correct and appropriately specific process term for the E1beta subunit of the PDC; consistent with experimental annotations to the same term and with the UniProt-curated function. Supporting Evidence: PMID:19081061 The human pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate to produce acetyl-CoA and NADH
GO:0045254 pyruvate dehydrogenase complex	IBA GO_REF:0000033	ACCEPT	Summary: PDHB is a structural component (E1beta) of the pyruvate dehydrogenase complex. This is a core, experimentally-corroborated cellular component annotation. Reason: PDHB is one of the two E1 subunits (alpha2-beta2) of the PDC; part_of the pyruvate dehydrogenase complex is the correct and specific component term. Supporting Evidence: PMID:19081061 The E1p component catalyzes the ThDP-mediated decarboxylation of pyruvate
GO:0004739 pyruvate dehydrogenase (acetyl-transferring) activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion of the E1 catalytic activity (EC 1.2.4.1; RHEA 19189), the defining molecular function of PDHB acting within the E1 heterotetramer. Corroborated by experimental IDA/TAS annotations to the same term. Reason: Correct molecular function mapping (InterPro IPR027110, EC 1.2.4.1, RHEA 19189). The activity is a property of the alpha2-beta2 heterotetramer to which PDHB contributes; core function. Supporting Evidence: PMID:19081061 The E1p component catalyzes the ThDP-mediated decarboxylation of pyruvate
GO:0005759 mitochondrial matrix	IEA GO_REF:0000044	ACCEPT	Summary: PDHB localizes to the mitochondrial matrix, mapped from the UniProt Subcellular Location vocabulary. This is the correct, specific compartment for the PDC. Reason: Matches the curated UniProt subcellular location (Mitochondrion matrix) and the PDC's known compartment; more specific than the bare mitochondrion annotations. Supporting Evidence: PMID:19081061 the gate-keeper enzyme that strategically links glycolysis to the Krebs cycle and lipogenic pathways
GO:0006086 pyruvate decarboxylation to acetyl-CoA	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assertion (ARBA/InterPro/ortholog) of the core PDC process. Duplicate of the IBA/IDA annotations to the same term. Reason: Correct core process term; consistent with the experimental and phylogenetic annotations to GO:0006086. Supporting Evidence: PMID:19081061 The human pyruvate dehydrogenase complex (PDC) catalyzes the oxidative decarboxylation of pyruvate to produce acetyl-CoA and NADH
GO:0005515 protein binding	IPI PMID:12651851 Structural basis for flip-flop action of thiamin pyrophospha...	REMOVE	Summary: IntAct IPI capturing the E1beta-E1alpha (PDHB-PDHA1, WITH UniProtKB P08559) interaction from the crystal structure of the alpha2-beta2 heterotetrameric human E1. The interaction is real and central (E1 heterotetramer assembly), but the term "protein binding" is uninformative; the functional content is better captured by the pyruvate dehydrogenase complex / E1 heterotetramer terms and by core_functions. Reason: Bare protein binding is uninformative. The E1beta-E1alpha (PDHA1) heterotetramer contact is a genuine subunit-assembly interaction within the pyruvate dehydrogenase complex, which is represented by the complex cellular-component annotations; the paper supports no more specific molecular function for PDHB. Removal does not mean the interaction is false. Supporting Evidence: PMID:12651851 alpha2beta2-heterotetrameric human pyruvate dehydrogenase, this cofactor is used
GO:0005515 protein binding	IPI PMID:18206651 Binding of pyruvate dehydrogenase to the core of the human p...	REMOVE	Summary: IntAct IPI for the E1beta-E2 (PDHB-DLAT, WITH UniProtKB P10515) interaction; this study scanned the E1beta C-terminal surface for residues binding the E2 (DLAT) core. The interaction is biologically meaningful (E1 docking onto the E2 core) but the GO term itself is uninformative. Reason: Bare protein binding is uninformative. The E1beta (PDHB) to E2 (DLAT) E1-binding-domain contact is a genuine subunit-assembly interaction within the pyruvate dehydrogenase complex, which is represented by the complex cellular-component annotations; the paper supports no more specific molecular function for PDHB. Removal does not mean the interaction is false. Supporting Evidence: PMID:18206651 The C-terminal surface of the E1beta subunit was scanned for the
GO:0005515 protein binding	IPI PMID:29128334 A Map of Human Mitochondrial Protein Interactions Linked to ...	REMOVE	Summary: IntAct IPI (WITH UniProtKB P08559, PDHA1) from a large-scale mitochondrial protein-interaction map. Captures the PDHB-PDHA1 (E1 heterotetramer) interaction; the term is uninformative. Reason: Bare protein binding from a proteome-scale interaction screen is uninformative as a molecular function, and the screen supports no more specific activity for PDHB. Removal does not mean the reported interaction is false. Supporting Evidence: PMID:29128334 A Map of Human Mitochondrial Protein Interactions Linked to Neurodegeneration
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: IntAct IPI (WITH PDHA1 P08559 and DLAT P10515) from a proteome-scale interactome (BioPlex). Recovers the physiological E1alpha and E2 partners; the GO term itself is uninformative. Reason: Bare protein binding from a proteome-scale interaction screen is uninformative as a molecular function, and the screen supports no more specific activity for PDHB. Removal does not mean the reported interaction is false. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome
GO:0005739 mitochondrion	NAS PMID:24534072 Component co-expression and purification of recombinant huma...	KEEP AS NON CORE	Summary: ComplexPortal NAS for mitochondrial localization, consistent with the PDC being a mitochondrial matrix enzyme. Correct but less specific than the mitochondrial matrix annotations. Reason: The broader mitochondrion term is correct but superseded by the more specific GO:0005759 mitochondrial matrix; retained as non-core supporting localization. Supporting Evidence: PMID:24534072 plays a key role in the conversion of pyruvate to
GO:0006086 pyruvate decarboxylation to acetyl-CoA	IDA PMID:19081061 Structural basis for inactivation of the human pyruvate dehy...	ACCEPT	Summary: Direct experimental (ComplexPortal IDA) annotation to the core PDC process, from the crystallographic/functional analysis of the human E1 component. Core biological process for PDHB. Reason: Strongly supported experimental annotation to the correct, specific process term; the paper directly characterizes E1-catalysed decarboxylation of pyruvate within the PDC. Supporting Evidence: PMID:19081061 The E1p component catalyzes the ThDP-mediated decarboxylation of pyruvate
GO:0006086 pyruvate decarboxylation to acetyl-CoA	IDA PMID:24534072 Component co-expression and purification of recombinant huma...	ACCEPT	Summary: ComplexPortal IDA to the core PDC process, based on recombinant human PDC (co-expressed components) shown to be functional in a pyruvate-to-acetyl-CoA assay. Core biological process. Reason: Experimental support for PDHB's participation in the conversion of pyruvate to acetyl-CoA within a reconstituted functional human PDC; correct and specific process term. Supporting Evidence: PMID:24534072 plays a key role in the conversion of pyruvate to
GO:0045254 pyruvate dehydrogenase complex	IDA PMID:19081061 Structural basis for inactivation of the human pyruvate dehy...	ACCEPT	Summary: Direct experimental (ComplexPortal IDA) evidence that PDHB is part of the pyruvate dehydrogenase complex, from structural analysis of the human E1 component. Core cellular component. Reason: PDHB (E1beta) is unambiguously part of the PDC; correct, specific component term with direct experimental support. Supporting Evidence: PMID:19081061 The E1p component catalyzes the ThDP-mediated decarboxylation of pyruvate
GO:0045254 pyruvate dehydrogenase complex	IPI PMID:19240034 Subunit and catalytic component stoichiometries of an in vit...	ACCEPT	Summary: ComplexPortal IPI (part_of PDC) from a study defining the subunit and catalytic-component stoichiometries of an in vitro reconstituted human PDC (40 E2p, 20 E3BP, 40 E1p, 20 E3). Confirms PDHB's incorporation into the assembled complex. Core cellular component. Reason: Directly demonstrates that E1 (of which PDHB is the beta subunit) is a stoichiometric component of the assembled human PDC; correct, specific term. Supporting Evidence: PMID:19240034 The human pyruvate dehydrogenase complex (PDC) is a 9.5-megadalton catalytic
GO:0005739 mitochondrion	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: HPA immunofluorescence IDA localizing PDHB to mitochondria. Correct but broader than the mitochondrial matrix annotations. Reason: Consistent with the curated matrix localization; kept as non-core supporting evidence, superseded in specificity by GO:0005759. Supporting Evidence: GO_REF:0000052 Gene Ontology annotation based on curation of immunofluorescence data
GO:0005759 mitochondrial matrix	ISS GO_REF:0000024	ACCEPT	Summary: Sequence-similarity (ISS, WITH UniProtKB P26284, pig ortholog) transfer of mitochondrial matrix localization. Correct and specific; consistent with the curated UniProt location. Reason: The matrix location is well established for the PDC; ISS transfer from a characterized mammalian ortholog is appropriate and specific. Supporting Evidence: PMID:19081061 the gate-keeper enzyme that strategically links glycolysis to the Krebs cycle and lipogenic pathways
GO:0004739 pyruvate dehydrogenase (acetyl-transferring) activity	IDA PMID:18164639 Mutations of the E1beta subunit gene (PDHB) in four families...	ACCEPT	Summary: MGI IDA (contributes_to) for E1 activity, from a study of PDHB mutations in PDC-deficient patients diagnosed by low PDC activity. The contributes_to qualifier correctly reflects that the acetyl-transferring activity is a property of the alpha2-beta2 heterotetramer to which PDHB contributes. Core molecular function. Reason: Loss-of-function PDHB variants reduce PDC (E1) activity, directly linking PDHB to the catalytic activity; contributes_to is the appropriate qualifier for a subunit of a multi-subunit enzyme. Supporting Evidence: PMID:18164639 All cases were diagnosed by low PDC activity, with normal E2 and E3
GO:0006086 pyruvate decarboxylation to acetyl-CoA	IC PMID:18164639 Mutations of the E1beta subunit gene (PDHB) in four families...	ACCEPT	Summary: MGI IC (inferred from the GO:0004739 activity annotation) placing PDHB upstream of/within the pyruvate-to-acetyl-CoA process. Core process; consistent with the disease evidence that PDHB defects impair PDC flux. Reason: Reasonable curator inference from the E1 activity annotation; the process term is correct and central to PDHB function. Supporting Evidence: PMID:18164639 found four cases of PDHB mutations among 83 analyzed cases of PDC deficiency
GO:0005739 mitochondrion	IDA PMID:2295468 Isolation of tryptic fragment of antigen from mitochondrial ...	KEEP AS NON CORE	Summary: UniProt IDA (is_active_in mitochondrion). This is the paper from which UniProt curated direct protein sequencing of the mature PDHB N-terminus (residues 31-55); PDHB is a mitochondrial matrix enzyme, so is_active_in mitochondrion is appropriate. The abstract foregrounds an E2 subunit-binding domain, but the curator used the full data (direct PDHB protein sequence). Reason: Correct compartment but broader than the specific matrix location; retained as non-core. Not removed - this is an experimental annotation whose full data (direct protein sequencing of PDHB) was seen by the UniProt curator. Supporting Evidence: PMID:2295468 the subunit binding domain of the pyruvate dehydrogenase complex E2 from bovine
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	KEEP AS NON CORE	Summary: High-throughput mitochondrial proteome evidence for mitochondrial localization of PDHB. Correct but broader than the matrix annotations. Reason: Consistent with the known matrix localization; retained as non-core supporting evidence, less specific than GO:0005759. Supporting Evidence: PMID:34800366 Quantitative high-confidence human mitochondrial proteome and its dynamics
GO:0004739 pyruvate dehydrogenase (acetyl-transferring) activity	IDA PMID:19081061 Structural basis for inactivation of the human pyruvate dehy...	ACCEPT	Summary: UniProt IDA (contributes_to) for the E1 catalytic activity, from the crystallographic/functional study of the human E1 component; the E1 subunit catalyses TPP-dependent decarboxylation of pyruvate and reductive acetylation of the E2 lipoyl group. Core molecular function. Reason: Direct experimental characterization of E1 catalysis; contributes_to correctly reflects PDHB as one subunit of the catalytic alpha2-beta2 E1 heterotetramer. Supporting Evidence: PMID:19081061 reductive acetylation of a lipoyl group
GO:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus.	MARK AS OVER ANNOTATED	Summary: Single high-throughput hit from a human sperm-nucleus proteomics dataset (403 proteins identified). PDHB is a mitochondrial matrix enzyme; a nuclear assignment for this TPP-dependent PDC subunit is best explained as a large-scale dataset contaminant/over-annotation rather than a genuine nuclear function. Reason: No mechanistic or corroborating evidence for a nuclear role of PDHB; inconsistent with its established mitochondrial-matrix localization and PDC function. Flagged as over-annotation of a proteomics screen rather than removed. Supporting Evidence: PMID:21630459 different proteins have been identified from the isolated sperm nuclei
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-203946	ACCEPT	Summary: Reactome TAS placing PDHB in the mitochondrial matrix, in the context of PDK phosphorylation of the PDC E1 subunit. Correct, specific compartment. Reason: Correct matrix localization consistent with the curated UniProt location and the PDC's compartment. Supporting Evidence: PMID:19081061 the gate-keeper enzyme that strategically links glycolysis to the Krebs cycle and lipogenic pathways
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-204169	ACCEPT	Summary: Reactome TAS placing PDHB in the mitochondrial matrix, in the context of PDP1/2 dephosphorylation of the PDC. Correct, specific compartment. Reason: Correct matrix localization; consistent with the curated location. Supporting Evidence: PMID:19081061 the gate-keeper enzyme that strategically links glycolysis to the Krebs cycle and lipogenic pathways
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838035	ACCEPT	Summary: Reactome TAS for mitochondrial matrix localization, in a generic matrix-protein context (CLPXP binding matrix proteins). The compartment is correct; the reaction context is generic protein quality control, not PDC function. Reason: Matrix localization is correct and consistent with the curated location, even though the source reaction is generic matrix-protein quality control rather than PDC-specific biology. Supporting Evidence: PMID:19081061 the gate-keeper enzyme that strategically links glycolysis to the Krebs cycle and lipogenic pathways
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838081	ACCEPT	Summary: Reactome TAS for mitochondrial matrix localization, in a generic matrix-protein context (LONP1 degrading matrix proteins). Compartment correct; generic quality-control context. Reason: Correct matrix localization consistent with the curated location; source reaction is a generic degradation reaction rather than PDC function. Supporting Evidence: PMID:19081061 the gate-keeper enzyme that strategically links glycolysis to the Krebs cycle and lipogenic pathways
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838093	ACCEPT	Summary: Reactome TAS for mitochondrial matrix localization, in a generic matrix-protein context (LONP1 binding matrix proteins). Compartment correct; generic quality-control context. Reason: Correct matrix localization consistent with the curated location; source reaction is a generic protein-binding/degradation reaction rather than PDC function. Supporting Evidence: PMID:19081061 the gate-keeper enzyme that strategically links glycolysis to the Krebs cycle and lipogenic pathways
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9838289	ACCEPT	Summary: Reactome TAS for mitochondrial matrix localization, in a generic matrix-protein context (CLPXP degrading matrix proteins). Compartment correct; generic quality-control context. Reason: Correct matrix localization consistent with the curated location; source reaction is a generic degradation reaction rather than PDC function. Supporting Evidence: PMID:19081061 the gate-keeper enzyme that strategically links glycolysis to the Krebs cycle and lipogenic pathways
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9861616	ACCEPT	Summary: Reactome TAS for mitochondrial matrix localization, in the context of the PDC reaction cascade (DLD/E3 dehydrogenating dihydrolipoyl). Correct, specific compartment. Reason: Correct matrix localization within the PDC catalytic cascade context. Supporting Evidence: PMID:19081061 the gate-keeper enzyme that strategically links glycolysis to the Krebs cycle and lipogenic pathways
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9861667	ACCEPT	Summary: Reactome TAS for mitochondrial matrix localization, in the context of the PDC reaction cascade (DLAT/E2 transferring acetyl to CoA). Correct, specific compartment. Reason: Correct matrix localization within the PDC catalytic cascade context. Supporting Evidence: PMID:19081061 the gate-keeper enzyme that strategically links glycolysis to the Krebs cycle and lipogenic pathways
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-9861734	ACCEPT	Summary: Reactome TAS for mitochondrial matrix localization, in the context of the PDC E1 reaction itself (PDH E1 decarboxylates pyruvate, transferring acetyl to DLAT). Directly relevant to PDHB function; correct, specific compartment. Reason: Correct matrix localization in the exact reaction (E1 decarboxylation) that PDHB participates in; strongly relevant. Supporting Evidence: PMID:19081061 The E1p component catalyzes the ThDP-mediated decarboxylation of pyruvate
GO:0004739 pyruvate dehydrogenase (acetyl-transferring) activity	TAS PMID:2376596 Characterization of two cDNA clones for pyruvate dehydrogena...	ACCEPT	Summary: PINC/ProtInc TAS for the E1 acetyl-transferring activity, from the early characterization of human PDH E1beta cDNA. Core molecular function annotation (traceable author statement). Reason: Correct molecular function for the E1beta subunit; consistent with the experimental IDA annotations to the same term. Supporting Evidence: PMID:2376596 beta subunit gene is not a member of a multigene family
GO:0006099 tricarboxylic acid cycle	TAS PMID:2376596 Characterization of two cDNA clones for pyruvate dehydrogena...	MARK AS OVER ANNOTATED	Summary: PINC/ProtInc TAS annotating PDHB to the tricarboxylic acid cycle. The PDC provides acetyl-CoA that feeds the TCA cycle, but the pyruvate-to-acetyl-CoA reaction is the entry step preceding the cycle, not part of the TCA cycle proper. The cited paper concerns E1beta cDNA and a TCA-cycle-deficient fibroblast line. Reason: PDHB is the gateway feeding acetyl-CoA into the TCA cycle rather than a TCA-cycle enzyme; the more accurate process is pyruvate decarboxylation to acetyl-CoA (GO:0006086). Flagged as over-annotation of the general TCA-cycle term rather than removed, since PDC is metabolically adjacent to the cycle. Proposed replacements: pyruvate decarboxylation to acetyl-CoA Supporting Evidence: PMID:2376596 one tricarboxylic acid cycle deficient

Gene Description

Existing Annotations Review

Core Functions

References

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