EUG1 encodes a soluble endoplasmic-reticulum-lumen protein disulfide isomerase (PDI) family member with two atypical CXXS active-site motifs. Eug1p is induced when proteins accumulate in the ER and participates in the cooperative redox folding of secretory-pathway clients. Native Eug1p has very weak classical oxidative-refolding and disulfide-isomerase activity relative to Pdi1p, and it cannot by itself supply all essential Pdi1p functions, indicating a specialized auxiliary role in ER protein folding.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: Eug1p is a soluble endoplasmic-reticulum protein. Reason: The phylogenetic localization is consistent with direct characterization of Eug1p as a soluble ER protein and with its ER-lumen retention signal. Supporting Evidence: PMID:1406650 The product of the EUG1 gene of Saccharomyces cerevisiae is a soluble endoplasmic reticulum protein |
| GO:0006457 protein folding | IBA GO_REF:0000033 | ACCEPT | Summary: Eug1p contributes to folding of proteins in the ER. Reason: Genetic defects in carboxypeptidase Y folding and biochemical oxidative-refolding activity support a role in protein folding, while the low native activity argues that this is an auxiliary rather than bulk Pdi1-like role. Supporting Evidence: PMID:11157982 Most mutant combinations show defects in carboxypeptidase Y folding as well as in glycan modification. |
| GO:0034976 response to endoplasmic reticulum stress | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: EUG1 is induced by accumulation of proteins in the ER. Reason: EUG1 expression is strongly induced during ER protein accumulation, so the response annotation is supported. It is non-core because Eug1p is a downstream ER folding/redox effector rather than a stress sensor or UPR signaling component. Supporting Evidence: PMID:1406650 EUG1 mRNA and protein levels are dramatically increased in response to the accumulation of native or unglycosylated proteins in the endoplasmic reticulum. |
| GO:0003756 protein disulfide isomerase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Native Eug1p has weak but measurable protein disulfide isomerase-family activity. Reason: The family inference is supported by biochemical and genetic evidence, but native CXXS Eug1p is much less active than Pdi1p and general disulfide isomerization is unlikely to be its principal in-vivo role. Supporting Evidence: PMID:11485577 The wild-type protein showed very little activity, not only in oxidative refolding but also in assays where only isomerase activity was required. PMID:16002399 Mpd1p, Mpd2, and Eug1p exhibit activities of 13.8, 16.0, and 2.16%, respectively, compared with Pdi1p file:yeast/EUG1/EUG1-deep-research-falcon.md Eug1p supplies a specialized component of a cooperative redox network. |
| GO:0003756 protein disulfide isomerase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The specific PDI term is consistent with Eug1p family membership and measured activity. Reason: Retain the automated assignment with the important qualification that wild-type Eug1p has very weak activity and is not functionally interchangeable with the essential Pdi1p enzyme. Supporting Evidence: PMID:16002399 Mpd1p, Mpd2, and Eug1p exhibit activities of 13.8, 16.0, and 2.16%, respectively, compared with Pdi1p |
| GO:0005788 endoplasmic reticulum lumen | IEA GO_REF:0000044 | ACCEPT | Summary: Eug1p is a soluble ER-lumen protein. Reason: This more precise localization is consistent with direct ER characterization and the secretory-pathway folding role of the protein. Supporting Evidence: PMID:1406650 The product of the EUG1 gene of Saccharomyces cerevisiae is a soluble endoplasmic reticulum protein |
| GO:0006457 protein folding | IEA GO_REF:0000117 | ACCEPT | Summary: Eug1p participates in ER client-protein folding. Reason: The annotation is supported by CPY-folding phenotypes and limited oxidative-refolding activity. It should not be interpreted as evidence for an independent holdase/chaperone activity. Supporting Evidence: PMID:11157982 Most mutant combinations show defects in carboxypeptidase Y folding as well as in glycan modification. |
| GO:0015035 protein-disulfide reductase activity | IEA GO_REF:0000117 | ACCEPT | Summary: Curated experimental annotations support thiol-disulfide reductase activity for Eug1p. Reason: Retain the automated term because independent curated experimental annotations assign this activity to Eug1p. The cached 2005 abstract attributes the reductive-activity measurements to Kimura et al. 2004 (BBRC 320:359-365), which is not cached, so the assay details and physiological substrate specificity are not visible here. |
| GO:0016853 isomerase activity | IEA GO_REF:0000043 | MODIFY | Summary: The parent isomerase term is unnecessarily broad for a characterized PDI-family protein. Reason: Replace the generic catalytic-class term with protein disulfide isomerase activity, while preserving the caveat that wild-type Eug1p's native activity is weak. The replacement intentionally normalizes this broad parent annotation to the same specific term already used by the direct and phylogenetic annotations. Proposed replacements: protein disulfide isomerase activity Supporting Evidence: PMID:11485577 The wild-type protein showed very little activity, not only in oxidative refolding but also in assays where only isomerase activity was required. |
| GO:0051082 unfolded protein binding | IEA GO_REF:0000117 | UNDECIDED | Summary: The ARBA inference is plausible but too generic to resolve Eug1p's molecular function. Reason: This automated family-level term does not distinguish generic binding from Eug1p's specific PDI/redox-folding activity. The available evidence allows possible chaperone-like assistance, but the abstract-only cache does not resolve whether Eug1p directly performs the asserted binding function. |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | MARK AS OVER ANNOTATED | Summary: A high-throughput interaction does not define Eug1p's molecular function. Reason: Retain the interaction as experimental context, but generic protein binding is uninformative and should not be treated as a core function. |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: High-throughput localization to the ER agrees with direct characterization. Reason: The dataset is concordant with older direct evidence that Eug1p is a soluble ER protein; no conflict is apparent. Supporting Evidence: PMID:1406650 The product of the EUG1 gene of Saccharomyces cerevisiae is a soluble endoplasmic reticulum protein |
| GO:0005783 endoplasmic reticulum | HDA PMID:11914276 Subcellular localization of the yeast proteome. | ACCEPT | Summary: Proteome-scale localization to the ER agrees with direct characterization. Reason: The high-throughput observation is independently supported by the original characterization of Eug1p as a soluble ER protein. Supporting Evidence: PMID:1406650 The product of the EUG1 gene of Saccharomyces cerevisiae is a soluble endoplasmic reticulum protein |
| GO:0003756 protein disulfide isomerase activity | ISS PMID:11157982 Functional differences in yeast protein disulfide isomerases... | ACCEPT | Summary: Sequence similarity is supported by Eug1p's PDI-family motifs and genetic behavior. Reason: Retain the annotation, but do not infer functional interchangeability: suppression by EUG1 depends on endogenous CXXC-containing homologues. Supporting Evidence: PMID:11157982 the presence of endogenous homologues with a CXXC motif in the thioredoxin-like domain is required for suppression of a pdi1 deletion by EUG1 |
| GO:0015035 protein-disulfide reductase activity | ISS PMID:11157982 Functional differences in yeast protein disulfide isomerases... | ACCEPT | Summary: The reductase assignment is plausible for this thioredoxin-domain PDI-family protein. Reason: Retain this sequence-supported annotation in light of independent curated biochemical annotations, while recognizing that the cached genetic paper emphasizes noninterchangeable functions and does not itself expose a Eug1p reductase assay. |
| GO:0005515 protein binding | IPI PMID:16002399 Interactions among yeast protein-disulfide isomerase protein... | MARK AS OVER ANNOTATED | Summary: Eug1p interactions are experimentally reported, but generic protein binding is uninformative. Reason: The paper reports Eps1p interactions with Eug1p and other ER factors. This supports network context, not a useful standalone molecular-function description for Eug1p. Supporting Evidence: PMID:16002399 Eps1p interacts with Pdi1p, Eug1p, Mpd1p, and Kar2p |
| GO:0019153 protein-disulfide reductase (glutathione) activity | IDA PMID:16002399 Interactions among yeast protein-disulfide isomerase protein... | ACCEPT | Summary: Direct biochemical evidence supports reductase activity under the assay conditions. Reason: Defer to the curator's full-text assessment of the direct assay. The cached abstract attributes reductive-activity measurements to Kimura et al. 2004 (BBRC 320:359-365), which is not cached; the Eug1p assay and its glutathione specificity are therefore not visible here. |
| GO:0051082 unfolded protein binding | IDA PMID:16002399 Interactions among yeast protein-disulfide isomerase protein... | UNDECIDED | Summary: The abstract-only cache does not expose the Eug1p assay supporting this direct annotation. Reason: Defer to the curator who assessed the full text. The cached abstract's chaperone comparison concerns Eps1p, Pdi1p, and Mpd1p complexes and cannot be used to accept or reject an Eug1p unfolded-protein-binding assay. |
| GO:0003756 protein disulfide isomerase activity | IMP PMID:11157982 Functional differences in yeast protein disulfide isomerases... | ACCEPT | Summary: Genetic phenotypes support a PDI-family contribution to ER redox folding. Reason: Suppression and folding phenotypes support the activity, with the important limitation that EUG1 requires CXXC-containing partners and is not a complete substitute for PDI1. Supporting Evidence: PMID:11157982 This shows that the homologues are not functionally interchangeable. |
| GO:0003756 protein disulfide isomerase activity | IGI PMID:11157982 Functional differences in yeast protein disulfide isomerases... | ACCEPT | Summary: Genetic interactions reveal a cooperative PDI-family redox-folding function. Reason: The requirement for endogenous CXXC homologues when EUG1 suppresses pdi1 supports a cooperative PDI-family role rather than autonomous bulk Pdi1 activity. Supporting Evidence: PMID:11157982 the presence of endogenous homologues with a CXXC motif in the thioredoxin-like domain is required for suppression of a pdi1 deletion by EUG1 |
| GO:0003756 protein disulfide isomerase activity | IDA PMID:16002399 Interactions among yeast protein-disulfide isomerase protein... | ACCEPT | Summary: Direct assays detect weak oxidative-refolding activity for Eug1p. Reason: The biochemical activity is real but quantitatively small: the cached abstract reports Eug1p at 2.16% of Pdi1p oxidative-refolding activity. Supporting Evidence: PMID:16002399 Mpd1p, Mpd2, and Eug1p exhibit activities of 13.8, 16.0, and 2.16%, respectively, compared with Pdi1p |
| GO:0006457 protein folding | IGI PMID:11157982 Functional differences in yeast protein disulfide isomerases... | ACCEPT | Summary: PDI-family deletion combinations produce ER client-folding defects. Reason: The genetic evidence directly links the noninterchangeable PDI-family network containing Eug1p to carboxypeptidase Y folding. Supporting Evidence: PMID:11157982 Most mutant combinations show defects in carboxypeptidase Y folding as well as in glycan modification. |
| GO:0015035 protein-disulfide reductase activity | IGI PMID:11157982 Functional differences in yeast protein disulfide isomerases... | ACCEPT | Summary: Genetic interactions support a cooperative thiol-disulfide redox function. Reason: Retain the curator's genetic interpretation. The cached abstract supports a cooperative network in which Eug1p depends on CXXC-containing homologues for essential oxidation, but it does not independently expose a Eug1p reductase assay. |
| GO:0015035 protein-disulfide reductase activity | IDA PMID:16002399 Interactions among yeast protein-disulfide isomerase protein... | ACCEPT | Summary: Direct biochemical assays support reductive activity for Eug1p. Reason: Retain the curator's full-text-based direct annotation. The cached abstract attributes reductive-activity measurements to Kimura et al. 2004 (BBRC 320:359-365), which is not cached, so the Eug1p assay and any native substrate claim cannot be independently checked here. |
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Download this section (compressed HTML)Q: Which native ER client proteins depend selectively on Eug1p rather than Pdi1p, Mpd1p, Mpd2p, or Eps1p?
Q: Does native CXXS Eug1p primarily rearrange particular client disulfides, or does it have a distinct noncatalytic role not captured by current GO terms?
Experiment: Compare wild-type Eug1p and CXXC-engineered variants on identified native ER client substrates at endogenous expression, measuring oxidation state, folding kinetics, and secretion.
Experiment: Combine acute depletion of individual PDI-family members with client-level redox proteomics to identify Eug1p-selective substrates and distinguish catalytic cooperation from generic stress induction.
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