EGD2 encodes the alpha subunit of the yeast nascent polypeptide-associated complex (NAC). EGD2 pairs with the beta subunits EGD1 or BTT1 to form ribosome-associated NAC heterodimers that contact emerging nascent chains, modulate early cotranslational folding, and help prevent inappropriate targeting of ribosome-nascent-chain complexes to membranes. The lipid-binding annotations are retained as peripheral biochemical observations rather than the central NAC function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: EGD2 functions in the cytoplasm as the alpha subunit of ribosome-associated NAC. Reason: Yeast NAC acts on cytosolic ribosomes and EGD2 is the alpha subunit of the dominant alpha-beta NAC complex. |
| GO:0006612 protein targeting to membrane | IBA GO_REF:0000033 | ACCEPT | Summary: NAC contributes to nascent-chain targeting decisions at membranes. Reason: EGD2-containing NAC prevents inappropriate membrane targeting of signal-less ribosome-nascent-chain complexes and supports cotranslational targeting decisions. |
| GO:0051082 unfolded protein binding | IBA GO_REF:0000033 | MODIFY | Summary: Manual review: unfolded protein binding is better represented by a more specific replacement term for EGD2. Reason: EGD2 participates in NAC-mediated nascent-chain chaperone activity; protein folding chaperone is a more informative molecular function than generic unfolded protein binding. Proposed replacements: protein folding chaperone |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Manual review: nucleus may be context-dependent or peripheral for EGD2. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Manual review: cytoplasm is consistent with known biology of EGD2. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005854 nascent polypeptide-associated complex | IEA GO_REF:0000002 | ACCEPT | Summary: EGD2 is a core alpha subunit of yeast NAC. Reason: InterPro and primary literature identify EGD2 as the alpha-NAC subunit in yeast. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | ACCEPT | Summary: Manual review: protein transport is consistent with known biology of EGD2. Reason: EGD2-containing NAC contributes to cotranslational protein targeting decisions by preventing inappropriate ER membrane association of signal-less ribosome-nascent-chain complexes; the broad protein transport annotation is therefore biologically supported, though less informative than the specific NAC targeting and chaperone terms. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for EGD2. Reason: High-throughput protein-binding evidence is less informative than the specific NAC complex, ribosome-associated chaperone, and targeting functions. |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for EGD2. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:16926149 The yeast Ccr4-Not complex controls ubiquitination of the na... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for EGD2. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for EGD2. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for EGD2. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | MARK AS OVER ANNOTATED | Summary: Manual review: protein binding is too generic or over-extended for EGD2. Reason: Marked over-annotated because more specific terms capture the biology more accurately. |
| GO:0005737 cytoplasm | IDA PMID:10219998 Initial characterization of the nascent polypeptide-associat... | ACCEPT | Summary: Direct evidence places EGD2-containing NAC in the cytoplasmic ribosome-associated pool. Reason: PMID:10219998 supports cytosolic ribosome association for yeast NAC via beta subunits, with EGD2 as the alpha subunit in the complex. 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). |
| GO:0051083 'de novo' cotranslational protein folding | NAS PMID:26618777 Functional Dissection of the Nascent Polypeptide-Associated ... | ACCEPT | Summary: EGD2-containing NAC contributes to cotranslational folding and nascent-chain aggregation prevention. Reason: Functional dissection of yeast NAC supports ribosome-associated alpha-beta NAC as part of the nascent-chain chaperone network. The source GOA line uses NAS, and this review retains that evidence code rather than upgrading it, while noting that PMID:26618777 contains direct NAC functional assays supporting the biology. Supporting Evidence: PMID:26618777 Both, NAC and Ssb can interact directly with the nascent chain. file:yeast/EGD2/EGD2-deep-research-falcon.md Falcon literature synthesis supports EGD2 as alpha-NAC in ribosome-associated nascent-chain handling. |
| GO:0006613 cotranslational protein targeting to membrane | IGI PMID:10518932 The nascent polypeptide-associated complex (NAC) of yeast fu... | ACCEPT | Summary: Genetic evidence supports NAC function in cotranslational membrane targeting. Reason: EGD2-containing NAC helps prevent signal-less ribosome-nascent-chain complexes from binding ER membranes inappropriately. Supporting Evidence: PMID:10518932 In the absence of NAC, signal-less RNCs are able to bind to ER membranes. |
| GO:0005854 nascent polypeptide-associated complex | IDA PMID:10219998 Initial characterization of the nascent polypeptide-associat... | ACCEPT | Summary: IDA evidence supports EGD2 membership in NAC. Reason: EGD2 is the alpha subunit encoded in the yeast NAC locus set and forms alpha-beta NAC with EGD1 or BTT1. 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). file:interpro/panther/PTHR21713/PTHR21713-metadata.yaml PANTHER PTHR21713 identifies EGD2 in the nascent polypeptide associated complex alpha subunit-related family. |
| GO:0032266 phosphatidylinositol-3-phosphate binding | IDA PMID:16343487 Identification of novel phospholipid binding proteins in Sac... | KEEP AS NON CORE | Summary: Manual review: phosphatidylinositol-3-phosphate binding may be context-dependent or peripheral for EGD2. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0051082 unfolded protein binding | IMP PMID:9482879 The yeast nascent polypeptide-associated complex initiates p... | MODIFY | Summary: Manual review: unfolded protein binding is better represented by a more specific replacement term for EGD2. Reason: The evidence concerns NAC-mediated nascent-chain chaperone function and targeting, not generic binding to unfolded proteins. Proposed replacements: protein folding chaperone |
| GO:0070273 phosphatidylinositol-4-phosphate binding | IDA PMID:16343487 Identification of novel phospholipid binding proteins in Sac... | KEEP AS NON CORE | Summary: Manual review: phosphatidylinositol-4-phosphate binding may be context-dependent or peripheral for EGD2. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0070300 phosphatidic acid binding | IDA PMID:16343487 Identification of novel phospholipid binding proteins in Sac... | KEEP AS NON CORE | Summary: Manual review: phosphatidic acid binding may be context-dependent or peripheral for EGD2. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0080025 phosphatidylinositol-3,5-bisphosphate binding | IDA PMID:16343487 Identification of novel phospholipid binding proteins in Sac... | KEEP AS NON CORE | Summary: Manual review: phosphatidylinositol-3,5-bisphosphate binding may be context-dependent or peripheral for EGD2. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
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Experiment: Test EGD2 UBA-domain mutants for effects on nascent-chain aggregation, ribosome association, and cotranslational targeting in NAC/Ssb sensitized backgrounds.
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