BTT1 encodes the low-abundance beta-2 paralog of the yeast nascent-polypeptide-associated complex (NAC). Btt1 pairs with the alpha NAC subunit Egd2 to form an alternative NAC heterodimer that associates with cytosolic translating ribosomes near the nascent-chain exit tunnel. The best supported core functions are participation in the NAC complex, ribosome-linked cotranslational nascent-chain handling/folding, and regulation of cotranslational protein targeting to membranes. Btt1 also has reproducible physical and genetic links to Caf130/CCR4-NOT, but that appears to be a specialized or context-dependent regulatory role rather than the general NAC core function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005854 nascent polypeptide-associated complex | IBA GO_REF:0000033 | ACCEPT | Summary: The IBA annotation is consistent with Btt1's conserved NAC-beta family identity and with direct yeast experiments showing that BTT1 encodes one of the beta subunits of the nascent polypeptide-associated complex. Reason: Part_of NAC is a core cellular-component annotation for Btt1. It is supported by direct yeast IDA evidence and conserved NAC-family context. 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:yeast/BTT1/BTT1-deep-research-falcon.md Falcon identifies Btt1 as the low-abundance beta-2 paralog of yeast NAC. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: The cytosol IBA annotation is consistent with the cytosolic, ribosome-associated site of NAC action. Reason: Btt1 acts on cytosolic ribosome-nascent-chain complexes; cytosol is the appropriate core localization. Supporting Evidence: file:yeast/BTT1/BTT1-deep-research-falcon.md Falcon places Btt1's primary site of action at cytosolic ribosomes near the polypeptide exit tunnel. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt records possible transient nuclear localization by similarity, but the curated Btt1 evidence reviewed here primarily supports a cytosolic ribosome-associated NAC role. Reason: The nucleus annotation should not be elevated to core function for Btt1. It may reflect a minor or context-dependent localization of NAC-family proteins, while Btt1's best-supported activity is cytosolic and ribosome-proximal. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm is consistent with Btt1's placement in the cytosolic ribosome-associated NAC complex. Reason: Although cytosol is more precise, cytoplasm is not misleading for this protein and is consistent with UniProt localization and NAC biology. Supporting Evidence: file:yeast/BTT1/BTT1-deep-research-falcon.md Falcon describes Btt1 as acting primarily on cytosolic ribosomes. |
| GO:0005854 nascent polypeptide-associated complex | IEA GO_REF:0000117 | ACCEPT | Summary: The ARBA electronic annotation to NAC is consistent with direct IDA and IBA evidence for Btt1 as a NAC beta paralog. Reason: This electronic annotation is redundant with stronger evidence but correct and should be retained. 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:0006613 cotranslational protein targeting to membrane | IEA GO_REF:0000117 | ACCEPT | Summary: The ARBA annotation is consistent with direct yeast NAC evidence showing that NAC controls inappropriate ribosome-nascent-chain association with ER membranes. Reason: Cotranslational membrane targeting regulation is a legitimate NAC function. For Btt1 specifically, it should be interpreted as part of the NAC beta subunit's ribosome-associated role rather than as a standalone membrane transporter function. Supporting Evidence: PMID:10518932 We provide evidence that NAC prevents binding of RNCs without a signal sequence to yeast membranes. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | MODIFY | Summary: The UniProt keyword-derived protein transport annotation is too broad for Btt1. The supported transport-related role is cotranslational control of ribosome-nascent-chain targeting to membranes. Reason: Replace broad protein transport with GO:0006613 cotranslational protein targeting to membrane, which is already experimentally supported for yeast NAC and better captures the process represented by the annotation. Proposed replacements: cotranslational protein targeting to membrane Supporting Evidence: PMID:10518932 In the absence of NAC, signal-less RNCs are able to bind to ER membranes. |
| GO:0005515 protein binding | IPI PMID:11283351 A comprehensive two-hybrid analysis to explore the yeast pro... | MARK AS OVER ANNOTATED | Summary: This protein binding annotation comes from a large two-hybrid interactome screen and reports a generic Caf130 interaction. The interaction may be real, but GO:0005515 is not informative for Btt1 function. Reason: Generic protein binding should not be retained as a functional endpoint. The physiologically meaningful context is better represented by Btt1's NAC complex membership and by the non-core CCR4-NOT/Caf130 annotation. Supporting Evidence: PMID:11283351 A comprehensive two-hybrid analysis to explore the yeast protein interactome. |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | MARK AS OVER ANNOTATED | Summary: This interaction-derived GO:0005515 annotation is from global protein complex mapping. It is not wrong that Btt1 physically associates with proteins, but the term is too vague to describe Btt1's NAC biology. Reason: The supported interactions with CCR4, Caf130, and YJR011C should not be curated as generic protein binding. More informative annotations capture NAC complex membership and the contextual CCR4-NOT association. Supporting Evidence: PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | MARK AS OVER ANNOTATED | Summary: The 2023 proteome-scale interactome evidence supports physical association context but not a specific molecular function captured by GO:0005515. Reason: Protein binding is over-annotated because it does not identify what Btt1 does. The interaction information is better interpreted through NAC and CCR4-NOT context rather than as a standalone MF term. Supporting Evidence: PMID:37968396 The social and structural architecture of the yeast protein interactome. |
| GO:0051083 'de novo' cotranslational protein folding | NAS PMID:26618777 Functional Dissection of the Nascent Polypeptide-Associated ... | ACCEPT | Summary: The NAS annotation is consistent with the NAC complex functioning with other ribosome-associated chaperone systems to assist early folding of nascent polypeptides. Reason: Btt1-containing NAC is a ribosome-associated cotranslational proteostasis factor. Falcon and the 2015 NAC dissection support the view that Btt1 has weaker, more specialized activity than the major Egd1-containing NAC, but the process annotation remains appropriate. Supporting Evidence: PMID:26618777 assist cotranslational processes such as folding of nascent polypeptides. PMID:26618777 aggregation of newly synthesized proteins file:yeast/BTT1/BTT1-deep-research-falcon.md Falcon identifies Btt1 as a ribosome-associated NAC beta paralog involved in cotranslational nascent-chain handling. |
| GO:0006613 cotranslational protein targeting to membrane | IGI PMID:10518932 The nascent polypeptide-associated complex (NAC) of yeast fu... | ACCEPT | Summary: The IGI annotation captures the experimentally supported NAC role in preventing signal-less ribosome-nascent-chain complexes from binding ER membranes. Reason: This is a core NAC process and is supported by yeast-derived in vitro targeting experiments. For Btt1, it should be understood as a beta-subunit contribution to the NAC complex rather than a direct membrane-targeting receptor activity. Supporting Evidence: PMID:10518932 We provide evidence that NAC prevents binding of RNCs without a signal sequence to yeast membranes. PMID:10518932 In the absence of NAC, signal-less RNCs are able to bind to ER membranes. |
| GO:0030015 CCR4-NOT core complex | IPI PMID:18214544 Genome wide expression analysis of the CCR4-NOT complex indi... | KEEP AS NON CORE | Summary: Btt1 reproducibly interacts with Caf130 and was described as a tenth member of the CCR4-NOT complex. This is biologically meaningful, but the main evolved function of Btt1 remains NAC/ribosome-proximal cotranslational regulation. Reason: Retain the annotation as a non-core contextual complex association. The GO term may overstate Btt1 as part of the CCR4-NOT core relative to its low-abundance NAC beta-subunit identity, but the Caf130 interaction and CCR4-NOT regulatory context are well supported. Supporting Evidence: PMID:18214544 BTT1, a member of the nascent polypeptide association complex that binds the ribosome, was shown to be a tenth member of the CCR4-NOT complex PMID:18214544 interacting through CAF130 file:yeast/BTT1/BTT1-deep-research-falcon.md Falcon highlights Btt1-Caf130/CCR4-NOT coupling as a specialized, context-dependent regulatory role. |
| GO:0005854 nascent polypeptide-associated complex | IDA PMID:10219998 Initial characterization of the nascent polypeptide-associat... | ACCEPT | Summary: The original characterization directly supports BTT1 as encoding one of the yeast NAC beta subunits and places the complex on ribosomes close to nascent chains. Reason: This is direct experimental evidence for the central cellular-component annotation of Btt1. Supporting Evidence: PMID:10219998 BTT1). We found the complex bound to ribosomes via the beta-subunits PMID:10219998 in close proximity to nascent polypeptides |
| GO:0051082 unfolded protein binding | IMP PMID:10219998 Initial characterization of the nascent polypeptide-associat... | MODIFY | Summary: The original NAC study supports proximity to nascent polypeptides and a role in preventing mistargeting, but GO:0051082 is too vague for Btt1. The better curation is ribosome-associated cotranslational nascent-chain handling, represented by ribosome binding plus cotranslational folding and membrane-targeting process annotations. Reason: Replace generic unfolded protein binding with the more directly supported MF GO:0043022 ribosome binding. Btt1 is a NAC beta subunit that anchors NAC at translating ribosomes, while the biological-process annotations capture the nascent-chain folding and targeting outcomes. Proposed replacements: ribosome binding Supporting Evidence: PMID:10219998 BTT1). We found the complex bound to ribosomes via the beta-subunits PMID:10219998 in close proximity to nascent polypeptides file:yeast/BTT1/BTT1-deep-research-falcon.md Falcon supports interpreting Btt1 as a ribosome-associated NAC beta subunit rather than a generic unfolded-protein binder. |
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Download this section (compressed HTML)Q: Should Btt1 receive a distinct curated annotation for Caf130/CCR4-NOT-linked cotranslational mRNA regulation of ribosomal protein production, separate from its core NAC complex annotations?
Suggested experts: Craig EA, Deuerling E, Collart MA
Experiment: Compare wild-type BTT1, ribosome-binding-defective BTT1 mutants, and Caf130-interface BTT1 mutants for NAC ribosome occupancy, nascent-chain aggregation, ER membrane mistargeting, and Caf130-dependent RPL4 mRNA decay.
Hypothesis: Btt1's low-abundance NAC beta-2 functions separate its general ribosome-associated NAC activity from its specialized Caf130/CCR4-NOT regulatory role.
Type: ribosome profiling and nascent-chain quality-control assay
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