BTF3 encodes the beta subunit of the nascent polypeptide-associated complex (NAC), a conserved ribosome-associated factor that helps sort emerging nascent chains and prevents inappropriate SRP-dependent delivery of non-secretory proteins to the ER. Human BTF3 is also reported in the nucleus and retains legacy transcription-factor literature, but its best-supported core role is cytoplasmic cotranslational nascent-peptide handling rather than broad transcriptional regulation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005854 nascent polypeptide-associated complex | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved NAC-complex membership is strongly supported for human BTF3 and matches the PN NAC-component placement. Reason: BTF3 is the human NAC-beta subunit; orthology-based propagation is consistent with direct human structural and UniProt evidence that BTF3 heterodimerizes with NACA in the nascent polypeptide-associated complex. Supporting Evidence: file:human/BTF3/BTF3-notes.md BTF3/P20290 is the human NAC-beta subunit and the NAC heterodimer associates with ribosomes through BTF3. file:human/BTF3/BTF3-deep-research-falcon.md human BTF3 (Basic Transcription Factor 3), which is also known as NAC-beta / NACB |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Cytosolic localization is consistent with the conserved ribosome-associated NAC role. Reason: The propagated cytosol annotation is supported by direct human localization evidence and by the fact that the NACA-BTF3 heterodimer acts on nascent chains emerging from cytosolic ribosomes. |
| GO:0005515 protein binding | IPI PMID:18433331 Identification of a novel transcriptional repressor (HEPIS) ... | MARK AS OVER ANNOTATED | Summary: The SARS nsp10 interaction paper supports a context-specific physical association, but protein binding is too generic to retain as a useful core MF annotation. Reason: The underlying study describes a specific viral-interaction context rather than a distinctive molecular function for BTF3; retaining generic protein binding would add little beyond an undifferentiated interaction claim. Supporting Evidence: PMID:18433331 we co-immunoprecipitated HEPIS with BTF3, a component of the RNA pol II initiation complex |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: A large-scale interactome map supports association data but not an informative BTF3-specific MF term. Reason: Proteome-scale interactome resources can justify partner lists, but generic protein binding is discouraged and does not capture the PN-relevant NAC biology. This PMID contributes two GOA interaction rows for distinct partners (TXLNA and TXLNB), but both claims reduce to the same non-informative generic binding assertion for BTF3. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: The BioPlex-style AP-MS network supports physical association but not a specific core MF for BTF3. Reason: This is another large-scale interaction dataset; it does not define a distinctive BTF3 molecular activity and is better treated as background association evidence than as GO protein binding. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization is plausible and supported by UniProt, but it is not the PN-core role for BTF3. Reason: Human BTF3 is reported in the nucleus, yet UniProt explicitly notes that the NACA heterodimer is cytoplasmic. The nuclear/transcriptional side of BTF3 should therefore be preserved as contextual rather than elevated to core proteostasis biology. Supporting Evidence: file:human/BTF3/BTF3-notes.md UniProt also reports BTF3 in both cytoplasm and nucleus, while noting that the heterodimer with NACA is cytoplasmic. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization is consistent with the NAC heterodimer and nascent-chain handling role. Reason: UniProt and experimental evidence both place BTF3 in the cytoplasm, which is the appropriate compartment for the NAC-dependent nascent-chain sorting function. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence supports cytosolic localization. Reason: Direct localization evidence is consistent with BTF3 acting on ribosome-emergent nascent chains in the cytosolic translation environment. |
| GO:0005737 cytoplasm | IDA PMID:10982809 The alpha and beta subunit of the nascent polypeptide-associ... | ACCEPT | Summary: The NAC functional paper directly supports cytoplasmic localization. Reason: PMID:10982809, as summarized in UniProt, places BTF3 in the cytoplasm and ties that location to the cytoplasmic NACA-BTF3 heterodimer. |
| GO:1905551 negative regulation of protein localization to endoplasmic reticulum | IDA PMID:10982809 The alpha and beta subunit of the nascent polypeptide-associ... | ACCEPT | Summary: This term captures the PN-relevant NAC role and is supported by the curated human literature summary. Reason: PMID:10982809 reports that both NAC subunits contribute to preventing inappropriate nascent-chain interactions and that betaNAC alone directly binds the ribosome and is sufficient to prevent ribosome binding to the ER membrane. That supports assigning this ER-targeting control process to BTF3 as the NAC-beta complex component in human. Supporting Evidence: PMID:10982809 both subunits are in direct contact with nascent polypeptide chains on the ribosome and that both contribute to the prevention of inappropriate interactions. However, betaNAC alone directly binds to the ribosome and is sufficient to prevent ribosome binding to the endoplasmic reticulum membrane. file:human/BTF3/BTF3-deep-research-falcon.md BTF3-NACA binding prevents inappropriate targeting of non-secretory nascent polypeptides from ribosomes to the ER |
| GO:0043022 ribosome binding | IDA PMID:10982809 The alpha and beta subunit of the nascent polypeptide-associ... | NEW | Summary: New annotation for BTF3's direct ribosome-binding molecular function. The Beatrix et al. abstract explicitly assigns ribosome binding to betaNAC, which fills the main missing MF gap in the current GOA. Reason: PMID:10982809 directly supports ribosome binding by the BTF3/NAC-beta subunit. This is a core MF for human BTF3 and is more specific and informative than the generic protein-binding annotations already reviewed. Supporting Evidence: PMID:10982809 However, betaNAC alone directly binds to the ribosome and is sufficient to prevent ribosome binding to the endoplasmic reticulum membrane. file:human/BTF3/BTF3-uniprot.txt NAC associates with ribosomes through the BTF3/NACB subunit. file:human/BTF3/BTF3-deep-research-falcon.md NAC is positioned at the ribosome exit tunnel and BTF3’s N-terminal tail extends into the tunnel |
| GO:0005515 protein binding | IPI PMID:30242148 Gap junction protein Connexin-43 is a direct transcriptional... | MARK AS OVER ANNOTATED | Summary: The Connexin-43 paper supports a contextual transcription-related interaction, but protein binding remains too generic for GO curation. Reason: PMID:30242148 is useful for contextual nuclear/transcription-related biology, not for defining a core BTF3 molecular function. Generic protein binding obscures that distinction. Supporting Evidence: file:human/BTF3/BTF3-notes.md PMID:30242148 supports a contextual transcription-related interaction for BTF3 rather than the PN core role. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Orthology-based nuclear localization is plausible but should remain non-core. Reason: The propagated nucleus annotation is not contradicted, but the strongest proteostasis evidence for BTF3 concerns the cytoplasmic NAC heterodimer. Nuclear presence is better retained as secondary context. |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | MARK AS OVER ANNOTATED | Summary: Global mRNA-interactome capture is insufficient here to establish a specific core RNA-binding function for BTF3. Reason: The accessible evidence shows BTF3 was recovered in a broad high-throughput RBP atlas, but that does not distinguish direct RNA recognition from indirect ribosome- or mRNP-associated capture. The term is therefore too strong as a standalone MF annotation. Supporting Evidence: file:human/BTF3/BTF3-notes.md The large-scale RNA interactome and protein-interactome papers support association calls but do not, from the accessible text here, define a specific core molecular function beyond NAC-linked nascent-chain handling. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MARK AS OVER ANNOTATED | Summary: The second interactome-capture paper has the same limitation as the Cell 2012 study for BTF3. Reason: Recovery in a global mRNA-bound proteome dataset does not by itself establish a well-defined, conserved RNA-binding molecular function for BTF3. |
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Download this section (compressed HTML)Q: Do human BTF3 isoforms partition NAC-linked cotranslational function versus contextual nuclear/transcription-related roles?
Q: Is the reported RNA binding of human BTF3 direct, or does it mainly reflect indirect capture through ribosome- or mRNP-associated proximity?
Experiment: Isoform-resolved complementation after BTF3 depletion, measuring NAC assembly, ribosome association, and mistargeting of non-secretory reporters to the ER.
Type: cell biology and rescue assay
Experiment: Orthogonal RNA-binding assays such as eCLIP or UV-crosslinking with ribosome disruption controls to test whether BTF3 directly binds RNA outside the NAC/ribosome context.
Type: RNA-binding validation
Experiment: Acute perturbation of BTF3 followed by ribosome profiling or SRP-engagement assays on secretory versus non-secretory nascent chains.
Type: cotranslational targeting assay
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