EGD1 encodes the beta-1 subunit of the yeast nascent polypeptide-associated complex (NAC). EGD1 pairs mainly with the alpha subunit EGD2 to form the abundant alpha-beta NAC heterodimer at the ribosomal exit tunnel. NAC contacts nascent polypeptides, prevents inappropriate interactions with cytosolic and ER targeting factors, supports early cotranslational folding/targeting decisions, and has additional non-core roles in selective autophagy phenotypes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005854 nascent polypeptide-associated complex | IBA GO_REF:0000033 | ACCEPT | Summary: EGD1 is a beta subunit of the yeast nascent polypeptide-associated complex. Reason: NAC contains EGD2 with either EGD1 or BTT1; EGD1 is the abundant beta-NAC subunit and binds ribosomes near nascent polypeptides. Supporting Evidence: PMID:10219998 The three subunits of the nascent polypeptide-associated complex (alpha, beta1, beta3) in Saccharomyces cerevisiae are encoded by three genes (EGD2, EGD1, BTT1). PMID:26618777 In contrast to other eukaryotic organisms, the Saccharomyces cerevisiae genome encodes three NAC subunits. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: EGD1 functions on cytosolic ribosomes as part of NAC. Reason: NAC associates with cytoplasmic ribosomes via beta subunits and contacts emerging nascent chains. Supporting Evidence: PMID:10219998 We found the complex bound to ribosomes via the beta-subunits in a salt-sensitive manner, in close proximity to nascent polypeptides. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization is reported but is not the core NAC function. Reason: EGD1/NAC may pass through the nucleus, but its primary molecular role is ribosome-associated nascent-chain handling in the cytosol. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization is consistent with ribosome-associated NAC function. Reason: EGD1-containing NAC acts at cytoplasmic ribosomes and prevents inappropriate nascent-chain interactions. |
| GO:0005854 nascent polypeptide-associated complex | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA NAC-complex annotation is correct for EGD1. Reason: EGD1 is a named NAC beta subunit and part of the dominant yeast alpha-beta NAC heterodimer. |
| GO:0006613 cotranslational protein targeting to membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: EGD1-containing NAC regulates cotranslational targeting to membranes. Reason: The yeast evidence for ER targeting comes from in vitro microsome assays, while in vivo NAC deletion studies did not detect an aberrant translocation phenotype; this is supported but secondary to NAC's core cotranslational chaperone role. Supporting Evidence: PMID:10518932 In the absence of NAC, signal-less RNCs are able to bind to ER membranes. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | ACCEPT | Summary: Broad protein transport is less precise than cotranslational targeting but still reflects NAC targeting function. Reason: EGD1/NAC influences nascent protein targeting to mitochondria and ER membranes; a more specific cotranslational targeting term is already present. |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is not informative for EGD1. Reason: Large-scale complex evidence does not describe a specific molecular binding activity beyond NAC complex membership and ribosome/nascent-chain function. |
| GO:0005515 protein binding | IPI PMID:16926149 The yeast Ccr4-Not complex controls ubiquitination of the na... | MARK AS OVER ANNOTATED | Summary: CCR4-NOT interaction evidence is real but generic protein binding is too broad. Reason: PMID:16926149 supports association of NAC-EGD with CCR4-NOT and ubiquitination control, but the GO term protein binding obscures the more precise NAC complex role. |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | MARK AS OVER ANNOTATED | Summary: Binary interactome evidence should not be retained as a core generic binding function. Reason: The curated molecular role is NAC-mediated nascent-chain handling, not undifferentiated protein binding. |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | MARK AS OVER ANNOTATED | Summary: Inter-species interaction evidence is too generic for useful EGD1 annotation. Reason: More specific terms capture EGD1 as a NAC subunit with cotranslational chaperone/targeting activity. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | MARK AS OVER ANNOTATED | Summary: Recent interactome evidence does not change the core EGD1 annotation. Reason: Generic protein-binding annotations from interactomes are less useful than NAC complex and nascent-chain function terms. |
| GO:0005737 cytoplasm | IDA PMID:10219998 Initial characterization of the nascent polypeptide-associat... | ACCEPT | Summary: Cytoplasmic localization is experimentally supported. Reason: Initial characterization of yeast NAC places EGD1-containing NAC on cytoplasmic ribosomes. |
| GO:0051083 'de novo' cotranslational protein folding | NAS PMID:26618777 Functional Dissection of the Nascent Polypeptide-Associated ... | ACCEPT | Summary: NAC participates in early cotranslational folding and aggregation prevention. Reason: Functional dissection shows beta-NAC can ameliorate nac/ssb growth and folding-stress phenotypes and reduce aggregation. Supporting Evidence: PMID:26618777 The beta-subunit of NAC is essential and sufficient to ameliorate growth. file:yeast/EGD1/EGD1-deep-research-falcon.md Falcon literature synthesis supports EGD1 as beta-NAC in ribosome-associated cotranslational nascent-chain handling. |
| GO:0000423 mitophagy | IMP PMID:38177147 The nascent polypeptide-associated complex subunit Egd1 is r... | KEEP AS NON CORE | Summary: Mitophagy is supported but should remain non-core relative to NAC cotranslational function. Reason: egd1-null cells show reduced mitophagy, but the molecular mechanism is downstream and condition-specific compared with the core NAC chaperone role. Supporting Evidence: PMID:38177147 Mitophagy is strongly suppressed in cells lacking Egd1. |
| GO:0006613 cotranslational protein targeting to membrane | IGI PMID:10518932 The nascent polypeptide-associated complex (NAC) of yeast fu... | KEEP AS NON CORE | Summary: Genetic evidence supports NAC function in cotranslational membrane targeting. Reason: PMID:10518932 supports NAC effects on ER-membrane targeting in a cell-free system, but PMID:26618777 reports no aberrant translocation phenotype upon NAC deletion in yeast; retain as non-core. |
| GO:0016236 macroautophagy | IMP PMID:19793921 A genomic screen for yeast mutants defective in selective mi... | KEEP AS NON CORE | Summary: Macroautophagy is retained as a peripheral phenotype. Reason: Autophagy screens and EGD1-loss phenotypes indicate a role in selective/bulk autophagy efficiency, but this is not the principal molecular function. |
| GO:0005854 nascent polypeptide-associated complex | IDA PMID:10219998 Initial characterization of the nascent polypeptide-associat... | ACCEPT | Summary: IDA evidence supports EGD1 membership in the nascent polypeptide-associated complex. Reason: EGD1 beta-NAC is part of the ribosome-associated NAC complex. |
| GO:0051082 unfolded protein binding | IMP PMID:9482879 The yeast nascent polypeptide-associated complex initiates p... | MODIFY | Summary: Generic unfolded-protein binding should be replaced by cotranslational folding/chaperone activity. Reason: EGD1-containing NAC binds nascent polypeptides at the ribosomal exit tunnel and prevents inappropriate interactions; GO:0044183 better captures the molecular chaperone activity. Proposed replacements: protein folding chaperone |
Loading supporting content…
Download this section (compressed HTML)Q: Should EGD1's mitophagy phenotype be represented only as non-core, or does newer evidence justify a more mechanistic autophagy-related annotation?
Experiment: Use EGD1 ribosome-binding mutants to separate nascent-chain chaperone activity from mitophagy phenotypes under respiratory growth.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)