ERR1 (Enolase-related protein 1; systematic name YOR393W) is one of three near-identical Enolase-Related Region (ERR) proteins of Saccharomyces cerevisiae (ERR1/ERR2/ERR3), encoded at conserved sub-telomeric loci and found in all S. cerevisiae strains examined. The 437-residue protein has the complete two-domain enolase fold (an N-terminal capping domain and a C-terminal TIM-barrel) and retains every canonical catalytic and metal-binding residue of the enolase family, including the Glu proton donor, the Lys proton acceptor, and the aspartate/glutamate/aspartate Mg2+-binding triad. On this basis it is predicted to be a Mg2+-dependent phosphopyruvate hydratase (enolase, EC 4.2.1.11), catalysing the interconversion of 2-phospho-D-glycerate and phosphoenolpyruvate. It is closely related to but distinct from the two abundant glycolytic enolases ENO1 and ENO2 (about 67-68% identical), and its own protein sequence is essentially identical to ERR2 (100%) and ERR3 (about 99.5%). The protein has not been directly characterized experimentally (protein existence is inferred from homology), so its enzymatic activity in vivo, its physiological role, its expression conditions, and its subcellular localization remain undetermined.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004634 phosphopyruvate hydratase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) propagation of the enolase molecular function from the PANTHER enolase family, whose source genes include the characterized yeast and mammalian enolases. This molecular-function prediction is domain-defensible: ERR1 carries the complete enolase fold with all catalytic residues (E212 proton donor, K346 proton acceptor) and the Mg2+-binding triad intact, so it retains the capacity for enolase catalysis. Reason: The predicted molecular function is consistent with a fully conserved enolase active site. This represents the best-supported (though homology-based, PE 3) statement of ERR1's likely activity. Note this is capacity inferred from sequence/structure; no in-vivo or purified-protein enzyme assay for ERR1 exists. Supporting Evidence: file:yeast/ERR1/ERR1-uniprot.txt SIMILARITY: Belongs to the enolase family. |
| GO:0006096 glycolytic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic propagation of the glycolytic-process biological role from the enolase family. Whereas the molecular function is defensible from residue conservation, the physiological claim that ERR1 actually participates in glycolytic flux in vivo is unproven. The characterized glycolytic enolases of S. cerevisiae are ENO1 and ENO2; the ERR paralogs are distinct sub-telomeric genes of uncertain physiological role and are not part of the characterized core glycolytic machinery. Reason: Retain as a family-level expectation rather than an established core function. Attributing glycolytic flux to ERR1 specifically over-reaches the evidence: the role, expression condition, and whether ERR1 is catalytically active in vivo are all undetermined (see knowledge_gaps). Marked non-core to avoid asserting an unverified in-vivo process for this dark paralog. Supporting Evidence: file:yeast/ERR1/ERR1-uniprot.txt PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D- |
| GO:0000015 phosphopyruvate hydratase complex | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Enolases act as oligomers constituting the phosphopyruvate hydratase complex, and this cellular-component term is propagated phylogenetically from the family. For a catalytically-competent enolase this is a reasonable prediction, but whether ERR1 forms or joins such a complex in vivo (with itself, with other ERR proteins, or with ENO1/ENO2) has not been demonstrated. Reason: Plausible by homology but not experimentally established for ERR1; the subcellular/complex context of ERR1 is unknown (GOA also carries an ND cellular_component annotation). Retained as a non-core, homology-level expectation. Supporting Evidence: file:yeast/ERR1/ERR1-uniprot.txt SIMILARITY: Belongs to the enolase family. |
| GO:0000015 phosphopyruvate hydratase complex | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Electronic (InterPro IPR000941 -> GO) assignment of the same phosphopyruvate hydratase complex term. Redundant electronic support for the phylogenetic annotation above; carries the same homology-level status and the same caveat that complex membership is not experimentally established for ERR1. Reason: Same cellular-component prediction as the IBA annotation, from InterPro. Plausible by homology, not verified for ERR1; retained as non-core. Supporting Evidence: file:yeast/ERR1/ERR1-uniprot.txt SIMILARITY: Belongs to the enolase family. |
| GO:0000287 magnesium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Mg2+ is the obligatory enolase cofactor. ERR1 conserves all three canonical Mg2+-coordinating residues (D247, E296, D321), identical to ENO2, so this molecular-function annotation is well supported by the domain/residue analysis. Reason: The metal-binding residues required for the enolase Mg2+ cofactor are fully conserved; this is a defensible molecular-function prediction consistent with the enolase fold. Supporting Evidence: file:yeast/ERR1/ERR1-uniprot.txt COFACTOR: |
| GO:0004634 phosphopyruvate hydratase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated electronic annotation (ARBA/EC 4.2.1.11/RHEA:10164/InterPro) of the enolase molecular function. Redundant with the IBA and ISA annotations of the same term; same homology-level status. Reason: Consistent electronic prediction of the enolase activity, corroborated by the conserved active site. Same molecular function as the IBA/ISA annotations. Supporting Evidence: file:yeast/ERR1/ERR1-uniprot.txt EC=4.2.1.11 |
| GO:0006096 glycolytic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic propagation of the glycolytic-process term (InterPro + UniPathway UPA00109). Redundant with the IBA glycolytic-process annotation; carries the same caveat that ERR1's in-vivo participation in glycolysis is unproven. Reason: Same over-reaching physiological claim as the IBA glycolytic-process annotation, here from an electronic pipeline. Retained as a non-core family-level expectation rather than an established ERR1 function. Supporting Evidence: file:yeast/ERR1/ERR1-uniprot.txt PATHWAY: Carbohydrate degradation; glycolysis; pyruvate from D- |
| GO:0004634 phosphopyruvate hydratase activity | ISA PMID:7785338 Sequence analysis of the right end of chromosome XV in Sacch... | ACCEPT | Summary: SGD sequence-similarity (ISA) annotation of enolase activity, using ENO1 (SGD:S000001217) and ENO2 (SGD:S000003486) as the with/from source genes and Pryde et al. 1995 as the reference. The reference establishes DNA-level identity to ENO1/ENO2 (61%/60%) and the sub-telomeric genomic location; the enzyme activity itself is inferred from that similarity, not assayed. The molecular function is domain-defensible (active site fully conserved). Reason: Per curation rules, an ISA annotation is not removed on paralog grounds; the molecular-function inference from close similarity to the true enolases is sound and consistent with the intact active site. Note the cited paper reports DNA sequence identity and genomic location, not an enzyme assay. Supporting Evidence: PMID:7785338 The first of these shows 61% and 60% DNA sequence identity to Enolases 1 and 2 respectively. |
| GO:0005575 cellular_component | ND GO_REF:0000015 | ACCEPT | Summary: Root cellular_component term with the ND ("no data") evidence code, recording that no subcellular localization data are curated for ERR1. This correctly reflects the current state of knowledge. Reason: ND root-term placeholder documenting the absence of localization data; appropriate to keep as-is for a dark gene with no experimental CC evidence. |
| GO:0008150 biological_process | ND GO_REF:0000015 | ACCEPT | Summary: Root biological_process term with the ND evidence code, recording that no curated biological-process data exist for ERR1. This honestly reflects the dark status of the gene. Reason: ND root-term placeholder documenting the absence of biological-process data; appropriate to keep as-is. |
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Download this section (compressed HTML)Q: Is ERR1 protein expressed and catalytically active as an enolase in vivo, and under which growth or developmental condition (e.g. sporulation, stress, respiratory growth)?
Q: Do the three ERR genes have any biological role distinct from ENO1/ENO2, and can any role be attributed to ERR1 specifically given that its protein sequence is identical to ERR2 and nearly identical to ERR3?
Experiment: Heterologously express and purify recombinant ERR1 and measure 2-phosphoglycerate dehydratase (enolase) activity and Mg2+ dependence in vitro, comparing kinetic parameters to purified ENO1/ENO2.
Hypothesis: ERR1 encodes a catalytically active Mg2+-dependent phosphopyruvate hydratase.
Type: enzyme assay
Experiment: Construct locus-specific single/double/triple ERR deletions (and ERR+ENO combinations) and phenotype across fermentative, respiratory, sporulation, and stress conditions; pair with an ORF-specific expression reporter and proteomics to detect ERR1-specific expression and any non-redundant phenotype.
Hypothesis: ERR1 has a condition-specific in-vivo role separable from ENO1/ENO2 and from the other ERR paralogs.
Type: genetic deletion and phenotyping
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: Whether ERR1 is catalytically active as a phosphopyruvate hydratase (enolase) in vivo is unknown. No purified-protein enzyme assay or in-vivo activity measurement attributable specifically to ERR1 has been reported.
OPEN BIOLOGY MF_DARK
What is known: The enolase fold is complete and every canonical catalytic residue (Glu212 proton donor, Lys346 proton acceptor) and Mg2+-binding residue (Asp247, Glu296, Asp321) is conserved identically to ENO2, so ERR1 has the structural capacity for catalysis and is not a degenerate pseudoenzyme. Protein existence is only inferred from homology (PE 3).
Significance: Distinguishes a genuine, expressed enolase isoform from a conserved-but-silent gene copy; determines whether the enolase MF annotations reflect real in-vivo function.
What would resolve it: Express and purify ERR1 protein and assay 2-phosphoglycerate dehydratase activity; and/or detect the protein and measure enolase activity from an ERR1-tagged strain.
Provenance (the field's own admissions):
Gap: The in-vivo biological role of ERR1 and the condition(s), if any, under which it is expressed are undetermined. It is not established that ERR1 contributes to glycolytic flux, and no ERR1-specific phenotype or expression dataset has been curated here.
OPEN BIOLOGY BP_DARK
What is known: The characterized glycolytic enolases of S. cerevisiae are ENO1 and ENO2; the three ERR genes are distinct sub-telomeric loci present in all strains, but their physiological function is uncharacterized. ERR1 has ND (no-data) annotations for both cellular_component and biological_process.
Significance: A conserved, strain-invariant sub-telomeric gene family with an intact enzyme fold but no known role is a candidate piece of the yeast "unknome"; resolving it would reveal why S. cerevisiae maintains extra enolase-like genes beyond ENO1/ENO2.
What would resolve it: Locus-specific deletion/phenotyping of ERR1 across conditions (fermentative, respiratory, sporulation, stress) with ERR2/ERR3 controls; condition-resolved transcriptomics/proteomics for the specific ORF.
Provenance (the field's own admissions):
Gap: Whether ERR1 has any function distinct from its paralogs ERR2 and ERR3, or from the true enolases ENO1/ENO2, cannot be determined from existing evidence, and no functional assay can attribute a phenotype to ERR1 rather than ERR2/ERR3 without locus-specific genetics.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: Inline sequence analysis shows the ERR1 protein is 100% identical to ERR2 and about 99.5% identical to ERR3 (differing by ~2 residues), and 67-68% identical to ENO1/ENO2. Because ERR1 and ERR2 are the same protein sequence, any protein-, sequence-, or most biochemistry-based evidence is intrinsically ERR-family-level, not ERR1-specific.
Significance: Determines whether the ERR trio is functionally redundant reserve/pseudogenic copies or encodes a distinct, possibly condition-specific, activity; also flags that all ERR1 annotations are really family-level attributions.
What would resolve it: Single, double, and triple ERR deletions plus ERR/ENO combinatorial deletions with condition panels; allele-/locus-specific expression reporters to separate the copies.
Provenance (the field's own admissions):
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