CNE1 encodes the budding yeast calnexin homolog, an ER membrane lectin chaperone of the calreticulin/calnexin family. Cne1 promotes ER protein quality control by binding glycosylated folding intermediates, assisting folding or retention of misfolded glycoproteins, and contributing to ER-associated degradation decisions. Direct biochemical evidence argues against annotating yeast Cne1 as a calcium-binding protein despite family-transfer annotations.
Definition: Binding to monoglucosylated N-linked glycan structures on glycoprotein folding intermediates in the endoplasmic reticulum.
Justification: Cne1p is a calnexin-family lectin chaperone whose relevant carbohydrate specificity is monoglucosylated glycoprotein/oligosaccharide recognition, which is more specific than broad carbohydrate binding.
Parent term: oligosaccharide binding
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006457 protein folding | IBA GO_REF:0000033 | ACCEPT | Summary: protein folding is a supported biological-process context for Cne1p as an ER lectin chaperone and quality-control factor. Reason: Direct yeast evidence supports Cne1p in ER folding/quality control and retention/elimination of misfolded glycoprotein clients via ER-associated degradation. Supporting Evidence: PMID:25229868 These results suggest that in yeasts, Cne1p interacts with misfolded lysozyme proteins possibly causing their retention in the ER and subsequent elimination via ER-associated degradation. file:yeast/CNE1/CNE1-deep-research-falcon.md CNE1 (P27825) encodes Cne1p |
| GO:0036503 ERAD pathway | IBA GO_REF:0000033 | ACCEPT | Summary: ERAD pathway is a supported biological-process context for Cne1p as an ER lectin chaperone and quality-control factor. Reason: Direct yeast evidence supports Cne1p in ER folding/quality control and retention/elimination of misfolded proteins. Supporting Evidence: PMID:25229868 These results suggest that in yeasts, Cne1p interacts with misfolded lysozyme proteins possibly causing their retention in the ER and subsequent elimination via ER-associated degradation. |
| GO:0005509 calcium ion binding | IBA GO_REF:0000033 | REMOVE | Summary: Direct Cne1p biochemical characterization did not detect Ca2+ binding, so family-transfer calcium ion binding should not be retained for yeast CNE1. Reason: The direct yeast study contradicts the inferred calcium-binding annotation; calnexin-family membership alone is insufficient evidence for this molecular function in Cne1p. Supporting Evidence: PMID:7814381 Ca2+ binding activity has not been detected for Cne1p. |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: endoplasmic reticulum membrane is supported for Cne1p, an ER membrane glycoprotein. Reason: Direct localization and membrane-association evidence places Cne1p in the ER membrane/ER quality-control compartment. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | REMOVE | Summary: Direct Cne1p biochemical characterization did not detect Ca2+ binding, so family-transfer calcium ion binding should not be retained for yeast CNE1. Reason: The direct yeast study contradicts the inferred calcium-binding annotation; calnexin-family membership alone is insufficient evidence for this molecular function in Cne1p. Supporting Evidence: PMID:7814381 Ca2+ binding activity has not been detected for Cne1p. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000002 | ACCEPT | Summary: endoplasmic reticulum is supported for Cne1p, an ER membrane glycoprotein. Reason: Direct localization and membrane-association evidence places Cne1p in the ER membrane/ER quality-control compartment. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: endoplasmic reticulum membrane is supported for Cne1p, an ER membrane glycoprotein. Reason: Direct localization and membrane-association evidence places Cne1p in the ER membrane/ER quality-control compartment. |
| GO:0006457 protein folding | IEA GO_REF:0000002 | ACCEPT | Summary: protein folding is a supported biological-process context for Cne1p as an ER lectin chaperone and quality-control factor. Reason: Direct yeast evidence supports Cne1p in ER folding/quality control and retention/elimination of misfolded proteins. |
| GO:0030246 carbohydrate binding | IEA GO_REF:0000043 | MODIFY | Summary: CNE1 has lectin-site evidence for monoglucosylated oligosaccharide/glycoprotein recognition, so carbohydrate binding is directionally correct but too broad. Reason: Use the more specific oligosaccharide binding term for the known calnexin lectin-site activity. Proposed replacements: oligosaccharide binding Supporting Evidence: PMID:15173200 the chaperone function of Cne1p was greatly affected in the presence of monoglucosylated oligosaccharides (G1M9) that specifically bind to the lectin site. |
| GO:0051082 unfolded protein binding | IEA GO_REF:0000002 | MODIFY | Summary: Cne1p has chaperone activity toward folding intermediates, but unfolded protein binding alone is a less informative representation of the ER lectin-chaperone function. Reason: Replace with protein folding chaperone, while separately capturing oligosaccharide/lectin binding in core function and proposed terminology. Proposed replacements: protein folding chaperone |
| GO:0036503 ERAD pathway | IMP PMID:7814381 Saccharomyces cerevisiae CNE1 encodes an endoplasmic reticul... | ACCEPT | Summary: ERAD pathway is supported for Cne1p through its interaction with unstable glycosylated client proteins and contribution to their ER retention/elimination. Reason: PMID:25229868 provides direct yeast evidence that Cne1p binds unstable lysozyme mutants and contributes to their retention and elimination via ER-associated degradation. Supporting Evidence: PMID:25229868 These results suggest that in yeasts, Cne1p interacts with misfolded lysozyme proteins possibly causing their retention in the ER and subsequent elimination via ER-associated degradation. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:7814381 Saccharomyces cerevisiae CNE1 encodes an endoplasmic reticul... | ACCEPT | Summary: endoplasmic reticulum membrane is supported for Cne1p, an ER membrane glycoprotein. Reason: Direct localization and membrane-association evidence places Cne1p in the ER membrane/ER quality-control compartment. Supporting Evidence: PMID:7814381 Localization of the Cne1p protein by differential and analytical subcellular fractionation as well as by confocal immunofluorescence microscopy showed that it was exclusively located in the endoplasmic reticulum (ER) |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: endoplasmic reticulum is consistent with the ER biology of CNE1 and is supported by the SWAT endomembrane localization library. Reason: Accept as supporting ER localization evidence, with gene-specific ER function anchored by the primary literature and UniProt record. Supporting Evidence: PMID:26928762 we constructed and investigated a library of |
| GO:0005515 protein binding | IPI PMID:16002399 Interactions among yeast protein-disulfide isomerase protein... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for the CNE1 interaction evidence with ER folding factors such as Mpd1/Eps1. Reason: The interaction evidence is best interpreted as part of the ER chaperone/oxidoreductase quality-control network, not as a standalone generic protein-binding function. Supporting Evidence: PMID:16002399 Mpd1p alone does not have chaperone activity but that it interacts with and inhibits the chaperone activity of Cne1p |
| GO:0005515 protein binding | IPI PMID:16002399 Interactions among yeast protein-disulfide isomerase protein... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for the CNE1 interaction evidence with ER folding factors such as Mpd1/Eps1. Reason: The interaction evidence is best interpreted as part of the ER chaperone/oxidoreductase quality-control network, not as a standalone generic protein-binding function. Supporting Evidence: PMID:16002399 Mpd1p alone does not have chaperone activity but that it interacts with and inhibits the chaperone activity of Cne1p |
| GO:0051082 unfolded protein binding | IDA PMID:16002399 Interactions among yeast protein-disulfide isomerase protein... | MODIFY | Summary: Cne1p has chaperone activity toward folding intermediates, but unfolded protein binding alone is a less informative representation of the ER lectin-chaperone function. Reason: Replace with protein folding chaperone, while separately capturing oligosaccharide/lectin binding in core function and proposed terminology. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:15173200 Cne1p effectively suppressed the thermal denaturation of CS and enhanced the refolding of thermally or chemically denatured CS in a concentration-dependent manner. |
| GO:0006457 protein folding | IMP PMID:15173200 Expression and characterization of Saccharomyces cerevisiae ... | ACCEPT | Summary: protein folding is a supported biological-process context for Cne1p as an ER lectin chaperone and quality-control factor. Reason: Direct yeast evidence supports Cne1p in ER folding/quality control and retention/elimination of misfolded proteins. Supporting Evidence: PMID:15173200 Cne1p effectively suppressed the thermal denaturation of CS and enhanced the refolding of thermally or chemically denatured CS in a concentration-dependent manner. |
| GO:0051082 unfolded protein binding | IMP PMID:15173200 Expression and characterization of Saccharomyces cerevisiae ... | MODIFY | Summary: Cne1p has chaperone activity toward folding intermediates, but unfolded protein binding alone is a less informative representation of the ER lectin-chaperone function. Reason: Replace with protein folding chaperone, while separately capturing oligosaccharide/lectin binding in core function and proposed terminology. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:15173200 Cne1p effectively suppressed the thermal denaturation of CS and enhanced the refolding of thermally or chemically denatured CS in a concentration-dependent manner. |
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Download this section (compressed HTML)Q: What are the endogenous yeast glycoprotein clients whose ER retention or ERAD depends directly on Cne1p lectin-chaperone activity?
Experiment: Use Cne1p proximity labeling or crosslinking immunoprecipitation under ER stress, with glycosylation-defective and lectin-site mutant controls, followed by quantitative client identification.
Hypothesis: Cne1p-dependent ERAD is selective for monoglucosylated glycoprotein clients rather than general unfolded proteins.
Type: proximity labeling and glycoprotein client proteomics
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