PDX1 (YGR193C) encodes protein X (E3-binding protein, E3BP), a non-catalytic subunit of the mitochondrial matrix pyruvate dehydrogenase (PDH) complex and the yeast counterpart of human PDHX. It contains an N-terminal lipoyl domain followed by a peripheral subunit-binding domain, but no acetyltransferase catalytic domain. About 12 Pdx1 molecules bind the 60-mer Lat1 (E2) core and tether 12 Lpd1 (E3) homodimers to it; the subunit-binding domain is essential for high-affinity E3 binding while the lipoyl domain is dispensable. pdx1 null cells are viable but their PDH complex lacks E3 and cannot oxidise pyruvate to acetyl-CoA, so Pdx1 is required for mitochondrial pyruvate decarboxylation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005198 structural molecule activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA structural molecule activity from PTN008381836 (yeast PDX1 as donor). Reflects the curated view that protein X has a structural (non-catalytic) role in the PDH complex. Reason: Consistent with the experimental structural role; the more informative description of the activity is E3 adaptor/tethering (see core_functions). Supporting Evidence: PMID:2007123 protein X apparently plays a structural role in the PDH complex; i.e., it binds and positions E3 to the E2 core, and this specific binding is essential for a functional PDH complex |
| GO:0005198 structural molecule activity | IDA PMID:2007123 Disruption and mutagenesis of the Saccharomyces cerevisiae P... | ACCEPT | Summary: Lawson et al. 1991 IDA: purified PDH complex from pdx1 cells lacks both protein X and E3, and the authors conclude protein X plays a structural role binding and positioning E3 on the E2 core. Reason: Curator reading of the paper's conclusion; non-catalytic structural/adaptor subunit. Supporting Evidence: PMID:2007123 protein X apparently plays a structural role in the PDH complex; i.e., it binds and positions E3 to the E2 core, and this specific binding is essential for a functional PDH complex PMID:2007123 The PDH complex isolated from the mutant cells contained pyruvate dehydrogenase (E1 alpha + E1 beta) and dihydrolipoamide acetyltransferase (E2) but lacked protein X and dihydrolipoamide dehydrogenase (E3) |
| GO:0005198 structural molecule activity | IMP PMID:2007123 Disruption and mutagenesis of the Saccharomyces cerevisiae P... | ACCEPT | Summary: Lawson et al. 1991 IMP: pdx1 disruption and deletion mutants (subunit-binding domain required, lipoyl domain dispensable). Reason: Supports a structural, non-catalytic role. Supporting Evidence: PMID:2007123 deletion of the putative subunit binding domain (residues approximately 144-180) of protein X resulted in loss of high-affinity binding of E3 and concomitant loss of overall activity of the PDH complex PMID:2007123 This observation indicates that the lipoyl domain, and its covalently bound lipoyl moiety, is not essential for protein X function |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | ACCEPT | Summary: Mitochondrial proteomics (PMID:14576278) detected Pdx1 in purified mitochondria. Consistent with its role in the matrix PDH complex. Reason: Correct organelle; matrix is the precise sub-compartment. Supporting Evidence: PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Mitochondrial proteomics (PMID:16823961) detected Pdx1 in purified mitochondria. Consistent with its role in the matrix PDH complex. Reason: Correct organelle; matrix is the precise sub-compartment. Supporting Evidence: PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics. |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Mitochondrial proteomics (PMID:24769239) detected Pdx1 in purified mitochondria. Consistent with its role in the matrix PDH complex. Reason: Correct organelle; matrix is the precise sub-compartment. Supporting Evidence: PMID:24769239 Quantitative variations of the mitochondrial proteome and phosphoproteome during fermentative and respiratory growth in Saccharomyces cerevisiae. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: IBA is_active_in mitochondrion from PTN000568044 (human/rat E2 components and yeast LAT1/PDX1). Correct. Reason: Correct. Supporting Evidence: file:yeast/PDX1/PDX1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix. |
| GO:0005739 mitochondrion | IDA PMID:18180296 Yeast pyruvate dehydrogenase complex is regulated by a conce... | ACCEPT | Summary: Gey et al. 2008 IDA: mitochondrial localisation in a study of PDH regulatory kinases/phosphatases (full text not seen). Consistent with all other data. Reason: Correct. Supporting Evidence: PMID:18180296 Both proteins are associated with the complex. |
| GO:0005739 mitochondrion | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA rule: mitochondrion. Correct. Reason: Correct. Supporting Evidence: file:yeast/PDX1/PDX1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix. |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell 'Mitochondrion matrix' mapping; Pdx1 has an N-terminal mitochondrial transit peptide and is part of the matrix PDH complex. Reason: Precise location. Supporting Evidence: file:yeast/PDX1/PDX1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion matrix. |
| GO:0006086 pyruvate decarboxylation to acetyl-CoA | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000568044. Correct: Pdx1 is required for PDH complex activity. Reason: Core process. Supporting Evidence: PMID:2007123 extracts of mitochondria from the mutant, in contrast to extracts of wild-type mitochondria, did not catalyze a CoA- and NAD(+)-linked oxidation of pyruvate |
| GO:0006086 pyruvate decarboxylation to acetyl-CoA | IDA PMID:2007123 Disruption and mutagenesis of the Saccharomyces cerevisiae P... | ACCEPT | Summary: Lawson et al. 1991 IDA: complexes lacking protein X do not oxidise pyruvate; restoring protein X restores activity. Reason: Core process. Supporting Evidence: PMID:2007123 extracts of mitochondria from the mutant, in contrast to extracts of wild-type mitochondria, did not catalyze a CoA- and NAD(+)-linked oxidation of pyruvate PMID:2007123 The PDH complex isolated from the mutant cells contained pyruvate dehydrogenase (E1 alpha + E1 beta) and dihydrolipoamide acetyltransferase (E2) but lacked protein X and dihydrolipoamide dehydrogenase (E3) |
| GO:0006086 pyruvate decarboxylation to acetyl-CoA | IDA PMID:7947791 Expression, purification, and characterization of the dihydr... | ACCEPT | Summary: Maeng et al. 1994 IDA: recombinant E3BP-E3 reconstitutes a functional PDH complex with E1-E2. Reason: Core process. Supporting Evidence: PMID:7947791 The E3BP-E3 complex combined rapidly with a pyruvate dehydrogenase (E1)-dihydrolipoamide acetyltransferase (E2) subcomplex (E1-E2 subcomplex) to reconstitute a functional PDH complex |
| GO:0006086 pyruvate decarboxylation to acetyl-CoA | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro IPR045257 (E2/Pdx1) mapping. Correct. Reason: Correct. Supporting Evidence: file:yeast/PDX1/PDX1-uniprot.txt FUNCTION: Required for anchoring dihydrolipoamide dehydrogenase (E3) to |
| GO:0006086 pyruvate decarboxylation to acetyl-CoA | IMP PMID:2007123 Disruption and mutagenesis of the Saccharomyces cerevisiae P... | ACCEPT | Summary: Lawson et al. 1991 IMP: pdx1 mitochondrial extracts cannot catalyse CoA- and NAD-linked pyruvate oxidation. Reason: Core process. Supporting Evidence: PMID:2007123 extracts of mitochondria from the mutant, in contrast to extracts of wild-type mitochondria, did not catalyze a CoA- and NAD(+)-linked oxidation of pyruvate |
| GO:0006086 pyruvate decarboxylation to acetyl-CoA | NAS PMID:18180296 Yeast pyruvate dehydrogenase complex is regulated by a conce... | ACCEPT | Summary: NAS from Gey et al. 2008 (PDH regulation by Pkp1/Pkp2/Ppp1/Ppp2). Statement-level support only, but correct. Reason: Correct; redundant with experimental annotations. Supporting Evidence: PMID:18180296 Both proteins are associated with the complex. |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | REMOVE | Summary: InterPro IPR004167 (peripheral subunit-binding domain) / IPR036625 (E3-binding domain superfamily) mapped to acyltransferase activity. Yeast Pdx1 (410 aa) has a lipoyl domain and a peripheral subunit-binding domain but no 2-oxoacid dehydrogenase acyltransferase catalytic domain is annotated, and protein X is a non-catalytic E3-binding subunit; its lipoyl domain is even dispensable for PDH function. Reason: Domain-to-function mapping transfers the E2 catalytic activity to the non-catalytic protein X. Supporting Evidence: PMID:2007123 This observation indicates that the lipoyl domain, and its covalently bound lipoyl moiety, is not essential for protein X function PMID:2007123 protein X apparently plays a structural role in the PDH complex; i.e., it binds and positions E3 to the E2 core, and this specific binding is essential for a functional PDH complex |
| GO:0045254 pyruvate dehydrogenase complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA part_of PDH complex (PTN000568044). Correct. Reason: Core complex membership. Supporting Evidence: PMID:2007123 The PDH complex isolated from the mutant cells contained pyruvate dehydrogenase (E1 alpha + E1 beta) and dihydrolipoamide acetyltransferase (E2) but lacked protein X and dihydrolipoamide dehydrogenase (E3) |
| GO:0045254 pyruvate dehydrogenase complex | IDA PMID:2007123 Disruption and mutagenesis of the Saccharomyces cerevisiae P... | ACCEPT | Summary: Lawson et al. 1991 IDA: protein X copurifies in the PDH complex. Reason: Core complex membership. Supporting Evidence: PMID:2007123 The PDH complex isolated from the mutant cells contained pyruvate dehydrogenase (E1 alpha + E1 beta) and dihydrolipoamide acetyltransferase (E2) but lacked protein X and dihydrolipoamide dehydrogenase (E3) |
| GO:0045254 pyruvate dehydrogenase complex | IDA PMID:7947791 Expression, purification, and characterization of the dihydr... | ACCEPT | Summary: Maeng et al. 1994 IDA: about 12 E3BP monomers bind the E1-E2 subcomplex with 12 E3 dimers. Reason: Core complex membership with stoichiometry. Supporting Evidence: PMID:7947791 The results showed that the E1-E2 subcomplex binds about 12 E3BP monomers attached to 12 E3 homodimers |
| GO:0045254 pyruvate dehydrogenase complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro IPR045257 mapping to PDH complex. Correct. Reason: Correct. Supporting Evidence: file:yeast/PDX1/PDX1-uniprot.txt FUNCTION: Required for anchoring dihydrolipoamide dehydrogenase (E3) to |
| GO:0045254 pyruvate dehydrogenase complex | IPI PMID:18180296 Yeast pyruvate dehydrogenase complex is regulated by a conce... | ACCEPT | Summary: Gey et al. 2008 IPI: Pdx1 identified with the PDH complex in proteomic analysis (full text not seen). Reason: Consistent. Supporting Evidence: PMID:18180296 Both proteins are associated with the complex. |
| GO:0045254 pyruvate dehydrogenase complex | IPI PMID:7947791 Expression, purification, and characterization of the dihydr... | ACCEPT | Summary: Maeng et al. 1994 IPI with LPD1 (E3, SGD:S000005015): co-expressed E3BP and E3 form a stable complex that assembles onto E1-E2. Reason: Direct evidence of E3 binding within the complex. Supporting Evidence: PMID:7947791 The E3BP-E3 complex combined rapidly with a pyruvate dehydrogenase (E1)-dihydrolipoamide acetyltransferase (E2) subcomplex (E1-E2 subcomplex) to reconstitute a functional PDH complex |
| GO:1902493 acetyltransferase complex | IEA GO_REF:0000117 | MODIFY | Summary: ARBA rule for acetyltransferase complex, a correct but generic ancestor of the pyruvate dehydrogenase complex. Reason: Use the specific complex. Proposed replacements: pyruvate dehydrogenase complex Supporting Evidence: PMID:2007123 The PDH complex isolated from the mutant cells contained pyruvate dehydrogenase (E1 alpha + E1 beta) and dihydrolipoamide acetyltransferase (E2) but lacked protein X and dihydrolipoamide dehydrogenase (E3) |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:2007123 Disruption and mutagenesis of the Saccharomyces cerevisiae P... | NEW | Summary: Protein X binds Lpd1 (E3) through its subunit-binding domain and docks it onto the Lat1 (E2) core; deleting the subunit-binding domain abolishes high-affinity E3 binding and PDH activity, and recombinant E3BP-E3 reconstitutes a functional complex. This tethering is better captured by an adaptor term than by the generic structural molecule activity, and matches the treatment of human PDHX. Reason: Adds the informative MF for the non-catalytic E3-binding subunit. Supporting Evidence: PMID:2007123 protein X apparently plays a structural role in the PDH complex; i.e., it binds and positions E3 to the E2 core, and this specific binding is essential for a functional PDH complex PMID:2007123 deletion of the putative subunit binding domain (residues approximately 144-180) of protein X resulted in loss of high-affinity binding of E3 and concomitant loss of overall activity of the PDH complex PMID:7947791 The E3BP-E3 complex combined rapidly with a pyruvate dehydrogenase (E1)-dihydrolipoamide acetyltransferase (E2) subcomplex (E1-E2 subcomplex) to reconstitute a functional PDH complex |
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E3-binding protein of the mitochondrial pyruvate dehydrogenase complex; plays a structural role in the complex by binding and positioning dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide acetyltransferase (E2) core
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