BAG6 is a multifunctional nucleo-cytoplasmic proteostasis factor that sits at the boundary between the GET pathway and ubiquitin-proteasome-associated quality control. In the cytosol, the BAG6/UBL4A/GET4 (BAT3) complex captures hydrophobic tail-anchored or otherwise mislocalized secretory proteins, promotes their handoff to TRC40/ASNA1 for post-translational delivery to the endoplasmic reticulum, and routes failed clients toward ubiquitin-proteasome degradation. BAG6 also acts as a holdase for retrotranslocated ERAD substrates and contributes to ER stress-induced pre-emptive quality control. Additional nuclear and extracellular roles, including p53 acetylation after DNA damage and exosomal NKp30 ligand activity, are supported in specific contexts but are not the core conserved proteostasis functions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0036503 ERAD pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Human BAG6 literature supports BAG6 complex function in ER-associated degradation (ERAD), so the phylogenetic propagation is directionally correct and consistent with the core proteostasis role. Reason: Bag6 keeps retrotranslocated hydrophobic clients soluble and engaged with ERAD machinery, matching ERAD pathway membership. |
| GO:0031593 polyubiquitin modification-dependent protein binding | IBA GO_REF:0000033 | REMOVE | Summary: BAG6 operates in ubiquitin-linked quality control, but the reviewed core papers support ligase/DUB recruitment and client triage rather than a well-demonstrated direct polyubiquitin-binding activity. Reason: The conserved BAG6 literature does not establish polyubiquitin-selective binding as a defensible core molecular function. |
| GO:0051787 misfolded protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic propagation agrees with the human holdase literature: BAG6 preferentially captures aggregation-prone hydrophobic or misfolded clients during quality control. Reason: This matches the experimentally supported BAG6 holdase role in ERAD and mislocalized-protein triage. |
| GO:0071818 BAT3 complex | IBA GO_REF:0000033 | ACCEPT | Summary: The phylogenetic BAT3 complex annotation agrees with multiple human studies placing BAG6 in a heterotrimeric BAG6/UBL4A/GET4(TRC35) complex. Reason: Complex membership is well supported and central to both GET-pathway and UPS-adjacent BAG6 functions. |
| GO:0001822 kidney development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Developmental annotations are plausible downstream consequences from mammalian loss-of-function studies, but they are not BAG6's core conserved proteostasis role. Reason: Keep as contextual biology rather than a core molecular/process function. |
| GO:0006511 ubiquitin-dependent protein catabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: BAG6 helps channel selected clients toward ubiquitin-dependent degradation, but this broad process term loses the more informative GET/ERAD/pre-emptive-QC context. Reason: Retain more specific proteostasis terms instead of this umbrella catabolic label. |
| GO:0007130 synaptonemal complex assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This reproductive annotation reflects secondary mammalian biology rather than BAG6's central proteostasis function. Reason: Treat as contextual/non-core. |
| GO:0007283 spermatogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This reproductive-process annotation is best treated as contextual because BAG6's conserved role is proteostasis triage, not gametogenesis machinery. Reason: Keep as non-core. |
| GO:0007420 brain development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Any developmental nervous-system consequence is downstream/contextual rather than part of BAG6's main evolved role. Reason: Keep as non-core. |
| GO:0030324 lung development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This developmental annotation reflects contextual organismal phenotypes rather than BAG6's core GET/UPS-boundary biology. Reason: Keep as non-core. |
| GO:0030544 Hsp70 protein binding | IEA GO_REF:0000107 | REMOVE | Summary: This looks like over-propagation from BAG family naming. BAG6 is explicitly not a canonical BAG-domain Hsp70 nucleotide-exchange factor. Reason: Structural work shows the BAG6 C terminus is a mock/noncanonical BAG-similar domain, so Hsp70 binding should not be assumed from family membership. |
| GO:0031593 polyubiquitin modification-dependent protein binding | IEA GO_REF:0000107 | REMOVE | Summary: This broad automated propagation is not well grounded in the direct BAG6 mechanistic literature. Reason: The reviewed papers support client triage with E3s and DUBs, not a specific polyubiquitin-binding activity. |
| GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This regulatory proteolysis term reflects secondary spermatogenic/HSPA2 biology rather than BAG6's central proteostasis role. Reason: Keep as contextual/non-core. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Apoptosis-related effects exist in some contexts, but this broad automated term is not the best summary of BAG6 function. Reason: Retain only as non-core context. |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: BAG6 contributes to selected proteasomal quality-control routes, but this automated term is broader and less informative than the specific BAG6-supported processes. Reason: Prefer ERAD, tail-anchored insertion, or ER-stress pre-emptive quality control terms. |
| GO:0045861 negative regulation of proteolysis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This negative-regulation term reflects context-specific stabilization biology rather than the main BAG6 proteostasis program. Reason: Keep as non-core. |
| GO:0045995 regulation of embryonic development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Embryonic-development phenotypes are contextual downstream consequences and not the core conserved BAG6 role. Reason: Keep as non-core. |
| GO:0050821 protein stabilization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Protein stabilization is context-specific for selected partners and not the best core descriptor of BAG6. Reason: Keep as non-core. |
| GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ER-stress apoptosis is a context-dependent consequence, not BAG6's principal conserved function. Reason: Keep as non-core. |
| GO:0070628 proteasome binding | IEA GO_REF:0000107 | REMOVE | Summary: The reviewed BAG6 papers place clients en route to the proteasome but do not establish a clean direct proteasome-binding activity. Reason: This term is too specific for the available evidence. |
| GO:0005515 protein binding | IPI PMID:14667819 Analysis of a high-throughput yeast two-hybrid system and it... | REMOVE | Summary: The source interaction is too generic to retain as a useful BAG6 annotation. Reason: GO:0005515 is uninformative here and BAG6 already has more specific mechanistically grounded annotations. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: The source interaction is too generic to retain as a useful BAG6 annotation. Reason: GO:0005515 is uninformative here and BAG6 already has more specific mechanistically grounded annotations. |
| GO:0005515 protein binding | IPI PMID:18852879 Dendritic cells release HLA-B-associated transcript-3 positi... | REMOVE | Summary: The exosome/NK paper supports a contextual receptor-ligand role, not a useful standalone generic protein-binding annotation. Reason: Retain the more specific immune-context terms instead. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: This generic interaction term adds no useful BAG6-specific functional information. Reason: Remove generic protein-binding carryover. |
| GO:0005515 protein binding | IPI PMID:22046132 The SARS-coronavirus-host interactome: identification of cyc... | REMOVE | Summary: This generic interaction term adds no useful BAG6-specific functional information. Reason: Remove generic protein-binding carryover. |
| GO:0005515 protein binding | IPI PMID:22807449 The stalk domain and the glycosylation status of the activat... | REMOVE | Summary: This generic interaction term adds no useful BAG6-specific functional information. Reason: Remove generic protein-binding carryover. |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | REMOVE | Summary: This generic interaction term adds no useful BAG6-specific functional information. Reason: Remove generic protein-binding carryover. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: This generic interaction term adds no useful BAG6-specific functional information. Reason: Remove generic protein-binding carryover. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: This generic interaction term adds no useful BAG6-specific functional information. Reason: Remove generic protein-binding carryover. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: This generic interaction term adds no useful BAG6-specific functional information. Reason: Remove generic protein-binding carryover. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: This generic interaction term adds no useful BAG6-specific functional information. Reason: Remove generic protein-binding carryover. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: This generic interaction term adds no useful BAG6-specific functional information. Reason: Remove generic protein-binding carryover. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Extracellular release is real but limited to stress/tumor exosome contexts rather than BAG6's main intracellular proteostasis role. Reason: Keep as contextual, non-core localization. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: BAG6 is a bona fide nucleo-cytoplasmic protein, and nuclear localization is repeatedly observed in the literature and UniProt curation. Reason: Nuclear localization is real even though the principal PN role is cytosolic. |
| GO:0005829 cytosol | IEA GO_REF:0000120 | ACCEPT | Summary: Cytosolic localization is central to BAG6 GET/ERAD/mislocalized-protein triage functions. Reason: The core proteostasis role depends on cytosolic BAG6 complex localization. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasmic signal is compatible with BAG6's documented nuclear pool and DNA-damage-associated functions. Reason: This is a defensible subnuclear localization. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Independent localization evidence also places BAG6 in the cytosol. Reason: This is fully consistent with the core proteostasis model. |
| GO:0005515 protein binding | IPI PMID:40105103 Definition of the human mitochondrial TOM interactome reveal... | REMOVE | Summary: This generic interaction term adds no useful BAG6-specific functional information. Reason: Remove generic protein-binding carryover. |
| GO:0140597 protein carrier chaperone | IDA PMID:21636303 A ubiquitin ligase-associated chaperone holdase maintains po... | ACCEPT | Summary: This is one of the strongest BAG6 annotations. The 2011 Mol Cell study directly supports a holdase/carrier role for retrotranslocated hydrophobic clients. Reason: Bag6 maintains aggregation-prone clients in an unfolded yet soluble state and helps deliver them within quality-control pathways. Supporting Evidence: file:human/BAG6/BAG6-deep-research-falcon.md BAG6 is widely characterized as a chaperone/holdase that binds exposed hydrophobic segments |
| GO:0005829 cytosol | NAS PMID:25535373 Bag6 complex contains a minimal tail-anchor-targeting module... | ACCEPT | Summary: Cytosolic localization is consistent with the tail-anchor-targeting complex architecture and broader BAG6 literature, even if this individual assertion is author statement-level. Reason: The BAG6 complex acts in the cytosol before ER insertion or proteasomal routing. |
| GO:0006511 ubiquitin-dependent protein catabolic process | IDA PMID:20676083 A ribosome-associating factor chaperones tail-anchored membr... | MODIFY | Summary: PMID:20676083 is about ribosome-associated capture and handoff of tail-anchored proteins to TRC40, not a generic ubiquitin-dependent catabolic process. Reason: Replace with the specific GET-pathway process terms directly supported by the paper; the separate ribosome-binding molecular function is already captured by its own annotation. Proposed replacements: tail-anchored membrane protein insertion into ER membrane |
| GO:0006620 post-translational protein targeting to endoplasmic reticulum membrane | IDA PMID:25535373 Bag6 complex contains a minimal tail-anchor-targeting module... | ACCEPT | Summary: This matches the PN GET-pathway mapping and the structural/biochemical literature on tail-anchor targeting. Reason: BAG6 participates in post-translational delivery of tail-anchored proteins toward the ER membrane. Supporting Evidence: file:human/BAG6/BAG6-deep-research-falcon.md BAG6 is embedded in this pathway as both a substrate-holding factor and a quality-control adaptor |
| GO:0031647 regulation of protein stability | IDA PMID:21636303 A ubiquitin ligase-associated chaperone holdase maintains po... | MODIFY | Summary: The paper supports holdase/chaperone behavior rather than a broad generic regulation-of-stability process. Reason: A molecular chaperone/carrier term is a more faithful representation of the evidence. Proposed replacements: protein carrier chaperone |
| GO:0048018 receptor ligand activity | IDA PMID:18852879 Dendritic cells release HLA-B-associated transcript-3 positi... | KEEP AS NON CORE | Summary: Exosomal BAG6 can act as an NKp30 ligand, but this immune signaling role is contextual and not the core conserved BAG6 function. Reason: Keep as non-core context. |
| GO:0051132 NK T cell activation | IDA PMID:18852879 Dendritic cells release HLA-B-associated transcript-3 positi... | MODIFY | Summary: The paper concerns NK-cell activation, not NK T-cell activation. Reason: Replace with natural killer cell activation to match the actual experiment. Proposed replacements: natural killer cell activation |
| GO:0036503 ERAD pathway | NAS PMID:21636303 A ubiquitin ligase-associated chaperone holdase maintains po... | ACCEPT | Summary: Although this is an author statement-level annotation, the underlying study directly demonstrates a BAG6 holdase role that improves ERAD efficiency. Reason: The evidence supports ERAD pathway participation. Supporting Evidence: file:human/BAG6/BAG6-deep-research-falcon.md BAG6 helps route failed membrane/secretory protein biogenesis products and certain ERAD substrates into ubiquitin-proteasome degradation |
| GO:0005515 protein binding | IPI PMID:25713138 Structure of a BAG6 (Bcl-2-associated athanogene 6)-Ubl4a (u... | REMOVE | Summary: The structural paper supports complex architecture and adaptor function, not a useful generic protein-binding annotation. Reason: Retain the specific adaptor/core-complex annotations instead. |
| GO:0060090 molecular adaptor activity | EXP PMID:25713138 Structure of a BAG6 (Bcl-2-associated athanogene 6)-Ubl4a (u... | ACCEPT | Summary: BAG6 organizes UBL4A and TRC35/GET4 and supports substrate handoff, which is well captured by molecular adaptor activity. Reason: This term fits BAG6's bridge/scaffold role at the GET-pathway and cytosolic quality-control boundary. Supporting Evidence: file:human/BAG6/BAG6-deep-research-falcon.md BAG6’s C-terminal region is a structural part of the substrate-loading complex |
| GO:0140677 molecular function activator activity | IEP PMID:25713138 Structure of a BAG6 (Bcl-2-associated athanogene 6)-Ubl4a (u... | REMOVE | Summary: The cited paper does not establish BAG6 as a direct molecular-function activator of another enzyme or receptor. Reason: This annotation overstates the structural/adaptor evidence. |
| GO:0005515 protein binding | IPI PMID:27113755 UBQLN4 recognizes mislocalized transmembrane domain proteins... | REMOVE | Summary: This generic interaction term adds no useful BAG6-specific functional information. Reason: Remove generic protein-binding carryover. |
| GO:0045995 regulation of embryonic development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Orthology-based developmental regulation is plausible but not part of BAG6's core proteostasis identity. Reason: Keep as non-core context. |
| GO:0005515 protein binding | IPI PMID:29042515 Structural basis for regulation of the nucleo-cytoplasmic di... | REMOVE | Summary: This paper is informative for localization regulation, but GO:0005515 remains too generic. Reason: Remove generic protein-binding carryover. |
| GO:0005634 nucleus | IDA PMID:29042515 Structural basis for regulation of the nucleo-cytoplasmic di... | ACCEPT | Summary: This study directly addresses BAG6 nucleo-cytoplasmic partitioning and supports nuclear localization. Reason: Nuclear BAG6 is real and regulated by TRC35/GET4 binding. |
| GO:0005829 cytosol | IDA PMID:29042515 Structural basis for regulation of the nucleo-cytoplasmic di... | ACCEPT | Summary: This study directly supports cytosolic retention of BAG6 by TRC35/GET4. Reason: Cytosolic BAG6 is the state associated with core proteostasis functions. |
| GO:0071816 tail-anchored membrane protein insertion into ER membrane | IDA PMID:25535373 Bag6 complex contains a minimal tail-anchor-targeting module... | ACCEPT | Summary: The minimal BAG6 complex directly supports transfer of tail-anchored substrates into the TRC40/GET pathway. Reason: This is core PN-supported biology. |
| GO:0005515 protein binding | IPI PMID:26876100 Selective Binding of AIRAPL Tandem UIMs to Lys48-Linked Tri-... | REMOVE | Summary: This generic interaction term adds no useful BAG6-specific functional information. Reason: Remove generic protein-binding carryover. |
| GO:0005515 protein binding | IPI PMID:14960581 Ricin triggers apoptotic morphological changes through caspa... | REMOVE | Summary: The ricin paper is informative for apoptosis context, but GO:0005515 remains too generic. Reason: Remove generic protein-binding carryover. |
| GO:0061857 endoplasmic reticulum stress-induced pre-emptive quality control | IMP PMID:26565908 Pre-emptive Quality Control Protects the ER from Protein Ove... | ACCEPT | Summary: This is a specific stress-responsive proteostasis process that the paper directly supports. Reason: Bag6 contributes to degradation of rerouted ER pre-emptive quality-control substrates under ER stress. Supporting Evidence: |
| GO:0010498 proteasomal protein catabolic process | IMP PMID:26565908 Pre-emptive Quality Control Protects the ER from Protein Ove... | MARK AS OVER ANNOTATED | Summary: The specific process shown in the paper is ER stress-induced pre-emptive quality control, not a generic proteasomal catabolic pathway in isolation. Reason: Keep the more specific GO:0061857 annotation instead. |
| GO:0036503 ERAD pathway | IMP PMID:26565908 Pre-emptive Quality Control Protects the ER from Protein Ove... | MODIFY | Summary: PMID:26565908 is about ER stress-induced pre-emptive quality control, which is related to but distinct from canonical ERAD. Reason: Replace with the specific ER pQC term. Proposed replacements: endoplasmic reticulum stress-induced pre-emptive quality control |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MARK AS OVER ANNOTATED | Summary: A broad membrane term is too imprecise for BAG6, which is mainly cytosolic/nuclear with regulated ER-membrane association in specific QC contexts. Reason: If membrane association is retained, it should be ER-membrane-specific rather than generic membrane. |
| GO:0002429 immune response-activating cell surface receptor signaling pathway | IDA PMID:18852879 Dendritic cells release HLA-B-associated transcript-3 positi... | KEEP AS NON CORE | Summary: This immune signaling annotation is supported in exosome/NK-cell contexts but is clearly contextual rather than core BAG6 biology. Reason: Keep as non-core. |
| GO:0005102 signaling receptor binding | IPI PMID:18852879 Dendritic cells release HLA-B-associated transcript-3 positi... | MODIFY | Summary: The immune paper is better captured by receptor ligand activity than a generic signaling receptor binding term. Reason: Replace with receptor ligand activity. Proposed replacements: receptor ligand activity |
| GO:0005634 nucleus | IDA PMID:14960581 Ricin triggers apoptotic morphological changes through caspa... | ACCEPT | Summary: The ricin study also observed nuclear BAG6, consistent with BAG6's established nucleo-cytoplasmic distribution. Reason: Nuclear localization is defensible. |
| GO:0006915 apoptotic process | IDA PMID:14960581 Ricin triggers apoptotic morphological changes through caspa... | KEEP AS NON CORE | Summary: Ricin-induced apoptosis is a real contextual role but not BAG6's core conserved proteostasis function. Reason: Keep as non-core. |
| GO:0030101 natural killer cell activation | IDA PMID:18852879 Dendritic cells release HLA-B-associated transcript-3 positi... | KEEP AS NON CORE | Summary: Natural killer cell activation is experimentally supported for exosomal BAG6 but remains a contextual immune role. Reason: Keep as non-core. |
| GO:0070062 extracellular exosome | IDA PMID:18852879 Dendritic cells release HLA-B-associated transcript-3 positi... | KEEP AS NON CORE | Summary: Exosomal BAG6 is experimentally documented, but this is a conditional extracellular context rather than the main cellular location. Reason: Keep as non-core localization. Supporting Evidence: |
| GO:0036503 ERAD pathway | IDA PMID:23129660 SGTA antagonizes BAG6-mediated protein triage. | MODIFY | Summary: This paper studies SGTA antagonism of BAG6-mediated triage of mislocalized proteins in the cytosol, not canonical ERAD. Reason: Replace with the narrower protein-quality-control term that better fits cytosolic degradation of mislocalized hydrophobic clients. Proposed replacements: protein quality control for misfolded or incompletely synthesized proteins |
| GO:0036503 ERAD pathway | IDA PMID:24981174 Cytosolic quality control of mislocalized proteins requires ... | MODIFY | Summary: PMID:24981174 defines RNF126-dependent cytosolic quality control of mislocalized proteins rather than general ERAD. Reason: Replace with the more specific protein-quality-control term rather than the broader ubiquitin-dependent catabolic umbrella term. Proposed replacements: protein quality control for misfolded or incompletely synthesized proteins |
| GO:1904294 positive regulation of ERAD pathway | IMP PMID:24424410 USP13 antagonizes gp78 to maintain functionality of a chaper... | MODIFY | Summary: BAG6 is part of ERAD-associated machinery; this paper mostly shows that USP13 preserves BAG6 complex function rather than BAG6 acting as an upstream regulator of ERAD. Reason: The direct BAG6 claim is better captured as ERAD pathway participation. Proposed replacements: ERAD pathway |
| GO:0005737 cytoplasm | IDA PMID:21636303 A ubiquitin ligase-associated chaperone holdase maintains po... | ACCEPT | Summary: Whole-cell cytoplasmic localization is fully consistent with the BAG6 complex's proteostasis role. Reason: This is a defensible localization term. |
| GO:0005515 protein binding | IPI PMID:25535373 Bag6 complex contains a minimal tail-anchor-targeting module... | REMOVE | Summary: The structural complex paper supports specific adaptor/complex roles, not generic protein binding. Reason: Remove generic protein-binding carryover. |
| GO:0071818 BAT3 complex | IDA PMID:25535373 Bag6 complex contains a minimal tail-anchor-targeting module... | ACCEPT | Summary: This paper directly analyzes the BAG6 heterotrimeric complex architecture. Reason: BAT3 complex membership is well supported. |
| GO:0005515 protein binding | IPI PMID:23246001 SGTA recognizes a noncanonical ubiquitin-like domain in the ... | REMOVE | Summary: This ERAD paper supports specific SGTA/BAG6 pathway functions rather than a useful generic binding term. Reason: Remove generic protein-binding carryover. |
| GO:0005829 cytosol | IDA PMID:23246001 SGTA recognizes a noncanonical ubiquitin-like domain in the ... | ACCEPT | Summary: The SGTA/BAG6 ERAD paper supports a cytosolic BAG6 pool. Reason: This matches the core QC role. |
| GO:0016020 membrane | IDA PMID:23246001 SGTA recognizes a noncanonical ubiquitin-like domain in the ... | MODIFY | Summary: The paper supports regulated ER-membrane association through ERAD machinery rather than a generic membrane localization. Reason: Use endoplasmic reticulum membrane as the more faithful location. Proposed replacements: endoplasmic reticulum membrane |
| GO:0005634 nucleus | IDA PMID:21636303 A ubiquitin ligase-associated chaperone holdase maintains po... | ACCEPT | Summary: The 2011 ERAD study notes nuclear sequestration when Trc35 is absent, consistent with BAG6's known dynamic localization. Reason: Nuclear localization is supported. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:21636303 A ubiquitin ligase-associated chaperone holdase maintains po... | ACCEPT | Summary: Bag6 physically associates with ERAD E3 ligases such as gp78/AMFR and SYVN1, which is central to its UPS-adjacent chaperone role. Reason: This specific binding term is mechanistically informative and supported. Supporting Evidence: |
| GO:0051787 misfolded protein binding | IDA PMID:21636303 A ubiquitin ligase-associated chaperone holdase maintains po... | ACCEPT | Summary: This is the key direct evidence for BAG6 recognizing aggregation-prone hydrophobic/misfolded clients. Reason: The term accurately captures BAG6 holdase specificity. Supporting Evidence: |
| GO:0071818 BAT3 complex | IDA PMID:21636303 A ubiquitin ligase-associated chaperone holdase maintains po... | ACCEPT | Summary: The paper directly studies the BAG6/Ubl4A/Trc35 complex. Reason: Complex membership is well supported. |
| GO:1990381 ubiquitin-specific protease binding | IPI PMID:24424410 USP13 antagonizes gp78 to maintain functionality of a chaper... | KEEP AS NON CORE | Summary: Direct interaction with USP13 is well supported, but this is a specific partner interaction rather than the best core BAG6 function summary. Reason: Keep as non-core mechanistic context. Supporting Evidence: |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:24981174 Cytosolic quality control of mislocalized proteins requires ... | ACCEPT | Summary: RNF126 recruitment to the BAG6 UBL domain is a core mechanistic part of mislocalized-protein triage. Reason: This specific ligase-binding annotation is supported and informative. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18765639 BAT3 and SET1A form a complex with CTCFL/BORIS to modulate H... | REMOVE | Summary: The chromatin-regulator interaction paper does not justify retaining a generic protein-binding term. Reason: Remove generic protein-binding carryover. |
| GO:0001822 kidney development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse-based developmental evidence is plausible but not core to human BAG6 proteostasis biology. Reason: Keep as non-core. |
| GO:0005515 protein binding | IPI PMID:17403783 HLA-B-associated transcript 3 (Bat3)/Scythe is essential for... | REMOVE | Summary: The p53 acetylation paper supports a specific nuclear scaffold role, not a useful generic protein-binding annotation. Reason: Remove generic protein-binding carryover. |
| GO:0005634 nucleus | IDA PMID:17403783 HLA-B-associated transcript 3 (Bat3)/Scythe is essential for... | ACCEPT | Summary: This paper supports nuclear BAG6 during DNA-damage signaling. Reason: Nuclear localization is well supported. |
| GO:0005829 cytosol | IDA PMID:17403783 HLA-B-associated transcript 3 (Bat3)/Scythe is essential for... | ACCEPT | Summary: This paper also supports the broader nucleo-cytoplasmic distribution of BAG6. Reason: Cytosolic BAG6 is consistent with its principal proteostasis role. |
| GO:0005829 cytosol | IDA PMID:20676083 A ribosome-associating factor chaperones tail-anchored membr... | ACCEPT | Summary: The ribosome-associated TA-targeting study places BAG6 complex function in the cytosol. Reason: Cytosolic localization is central to GET-pathway capture/handoff. |
| GO:0006511 ubiquitin-dependent protein catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The broad catabolic-process inference is directionally consistent with BAG6 QC biology but loses specificity. Reason: Keep as non-core rather than using it as a core summary term. |
| GO:0007130 synaptonemal complex assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Orthology-based reproductive biology is secondary/contextual. Reason: Keep as non-core. |
| GO:0007283 spermatogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Orthology-based reproductive biology is secondary/contextual. Reason: Keep as non-core. |
| GO:0007420 brain development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Orthology-based developmental biology is secondary/contextual. Reason: Keep as non-core. |
| GO:0018393 internal peptidyl-lysine acetylation | IDA PMID:17403783 HLA-B-associated transcript 3 (Bat3)/Scythe is essential for... | KEEP AS NON CORE | Summary: BAG6 scaffolds p300-dependent p53 acetylation after DNA damage, but this is a specialized nuclear stress-response role rather than the core proteostasis function. Reason: Keep as non-core context. Supporting Evidence: |
| GO:0030324 lung development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Orthology-based developmental biology is secondary/contextual. Reason: Keep as non-core. |
| GO:0031593 polyubiquitin modification-dependent protein binding | ISS GO_REF:0000024 | REMOVE | Summary: The BAG6 literature reviewed here does not provide a solid basis for a direct polyubiquitin-binding activity. Reason: Remove this inferred binding term. |
| GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: This reflects secondary stabilization biology rather than BAG6's central PN role. Reason: Keep as non-core. |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IMP PMID:17403783 HLA-B-associated transcript 3 (Bat3)/Scythe is essential for... | KEEP AS NON CORE | Summary: This DNA-damage apoptosis role is well supported but context-specific. Reason: Keep as non-core nuclear stress biology. Supporting Evidence: |
| GO:0043022 ribosome binding | IDA PMID:20676083 A ribosome-associating factor chaperones tail-anchored membr... | KEEP AS NON CORE | Summary: Ribosome association is an important mechanistic feature of the GET-pathway capture step, but it is not the best standalone summary of BAG6 core function. Reason: Keep as mechanistically informative but non-core. |
| GO:0045861 negative regulation of proteolysis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Secondary stabilization/proteolysis control is contextual rather than core. Reason: Keep as non-core. |
| GO:0050821 protein stabilization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Selected-client stabilization is context-specific and not the main BAG6 role. Reason: Keep as non-core. |
| GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ER-stress apoptosis is context-dependent and not BAG6's principal conserved function. Reason: Keep as non-core. |
| GO:0070628 proteasome binding | ISS GO_REF:0000024 | REMOVE | Summary: Direct proteasome binding is not clearly established by the BAG6 papers reviewed here. Reason: Remove the inferred binding term. |
| GO:0071816 tail-anchored membrane protein insertion into ER membrane | IDA PMID:20676083 A ribosome-associating factor chaperones tail-anchored membr... | ACCEPT | Summary: This is the direct GET-pathway core BAG6 process supported by the landmark ribosome-associated TA-targeting paper. Reason: The evidence specifically fits tail-anchored membrane protein insertion into the ER membrane. Supporting Evidence: |
| GO:0071818 BAT3 complex | IDA PMID:20676083 A ribosome-associating factor chaperones tail-anchored membr... | ACCEPT | Summary: The 2010 Nature study defines the Bat3/Trc35/Ubl4A complex as the relevant functional unit. Reason: BAT3 complex membership is directly supported. |
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