BAG6

Existing Annotations Review

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. Supporting Evidence: PMID:20676083 PMID:21636303 PMID:25535373 file:human/BAG6/BAG6-notes.md
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. Supporting Evidence: PMID:21636303 file:human/BAG6/BAG6-notes.md
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. Supporting Evidence: PMID:20676083 PMID:25535373
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. Supporting Evidence: PMID:25535373 PMID:25713138 file:human/BAG6/BAG6-notes.md
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: PMID:21636303 PMID:20676083
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: PMID:25535373 PMID:20676083
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. Supporting Evidence: PMID:18852879 PMID:18055229
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.
GO:0005515 protein binding	IPI PMID:25713138 Structure of a BAG6-Ubl4a complex reveals a novel binding in...	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-Ubl4a complex reveals a novel binding in...	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: PMID:25713138 PMID:25535373
GO:0140677 molecular function activator activity	IEP PMID:25713138 Structure of a BAG6-Ubl4a complex reveals a novel binding in...	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. Supporting Evidence: PMID:25535373 PMID:20676083
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: PMID:26565908
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. Supporting Evidence: PMID:18852879 PMID:18055229
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. Supporting Evidence: PMID:18852879 PMID:18055229
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: PMID:18852879
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: PMID:21636303
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: PMID:21636303
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: PMID:24424410
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: PMID:24981174
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: PMID:17403783
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: PMID:17403783
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: PMID:20676083
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.

📄 View Raw YAML

id: P46379
gene_symbol: BAG6
product_type: PROTEIN
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
alternative_products:
- name: '1'
  id: P46379-1
- name: '2'
  id: P46379-2
  sequence_note: VSP_015695
- name: '3'
  id: P46379-3
  sequence_note: VSP_015695, VSP_030519
- name: '4'
  id: P46379-4
  sequence_note: VSP_015695, VSP_045910, VSP_045911,
- name: '5'
  id: P46379-5
  sequence_note: VSP_015695, VSP_045913
references:
- id: file:human/BAG6/BAG6-notes.md
  title: BAG6 review notes
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data from
    the Human Protein Atlas
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
- id: PMID:20676083
  title: A ribosome-associating factor chaperones tail-anchored membrane proteins.
- id: PMID:21636303
  title: A ubiquitin ligase-associated chaperone holdase maintains polypeptides in
    soluble states for proteasome degradation.
- id: PMID:21743475
  title: Protein targeting and degradation are coupled for elimination of mislocalized
    proteins.
- id: PMID:23129660
  title: SGTA antagonizes BAG6-mediated protein triage.
- id: PMID:23665563
  title: A ubiquitin-like domain recruits an oligomeric chaperone to a retrotranslocation
    complex in endoplasmic reticulum-associated degradation.
- id: PMID:24424410
  title: USP13 antagonizes gp78 to maintain functionality of a chaperone in ER-associated
    degradation.
- id: PMID:24981174
  title: Cytosolic quality control of mislocalized proteins requires RNF126 recruitment
    to Bag6.
- id: PMID:25535373
  title: Bag6 complex contains a minimal tail-anchor-targeting module and a mock BAG
    domain.
- id: PMID:25713138
  title: Structure of a BAG6-Ubl4a complex reveals a novel binding interface that
    functions in tail-anchored protein biogenesis.
- id: PMID:29042515
  title: Structural basis for regulation of the nucleo-cytoplasmic distribution of
    Bag6 by TRC35.
- id: PMID:17403783
  title: HLA-B-associated transcript 3 (Bat3)/Scythe is essential for p300-mediated
    acetylation of p53.
- id: PMID:18055229
  title: Human leukocyte antigen-B-associated transcript 3 is released from tumor
    cells and engages the NKp30 receptor on natural killer cells.
- id: PMID:18852879
  title: Dendritic cells release HLA-B-associated transcript-3 positive exosomes to
    regulate natural killer function.
- id: PMID:14667819
  title: Analysis of a high-throughput yeast two-hybrid system and its use to predict
    the function of intracellular proteins encoded within the human MHC class III
    region.
- id: PMID:14960581
  title: Ricin triggers apoptotic morphological changes through caspase-3 cleavage
    of BAT3.
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
- id: PMID:18765639
  title: BAT3 and SET1A form a complex with CTCFL/BORIS to modulate H3K4 histone dimethylation
    and gene expression.
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
- id: PMID:21903422
  title: Mapping a dynamic innate immunity protein interaction network regulating
    type I interferon production.
- id: PMID:22046132
  title: 'The SARS-coronavirus-host interactome: identification of cyclophilins as
    target for pan-coronavirus inhibitors.'
- id: PMID:22807449
  title: The stalk domain and the glycosylation status of the activating natural killer
    cell receptor NKp30 are important for ligand binding.
- id: PMID:23246001
  title: SGTA recognizes a noncanonical ubiquitin-like domain in the Bag6-Ubl4A-Trc35
    complex to promote endoplasmic reticulum-associated degradation.
- id: PMID:25036637
  title: A quantitative chaperone interaction network reveals the architecture of
    cellular protein homeostasis pathways.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by stoichiometries
    and abundances.
- id: PMID:26876100
  title: Selective Binding of AIRAPL Tandem UIMs to Lys48-Linked Tri-Ubiquitin Chains.
- id: PMID:27113755
  title: UBQLN4 recognizes mislocalized transmembrane domain proteins and targets
    these to proteasomal degradation.
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the
    allele frequency spectrum in human populations.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
- id: PMID:40105103
  title: Definition of the human mitochondrial TOM interactome reveals TRABD as a
    new interacting protein.
- id: PMID:26565908
  title: Pre-emptive Quality Control Protects the ER from Protein Overload via the
    Proximity of ERAD Components and SRP.
existing_annotations:
- term:
    id: GO:0036503
    label: ERAD pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    reason: Bag6 keeps retrotranslocated hydrophobic clients soluble and engaged with
      ERAD machinery, matching ERAD pathway membership.
    supported_by:
    - reference_id: PMID:20676083
    - reference_id: PMID:21636303
    - reference_id: PMID:25535373
    - reference_id: file:human/BAG6/BAG6-notes.md
- term:
    id: GO:0031593
    label: polyubiquitin modification-dependent protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: REMOVE
    reason: The conserved BAG6 literature does not establish polyubiquitin-selective
      binding as a defensible core molecular function.
- term:
    id: GO:0051787
    label: misfolded protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Phylogenetic propagation agrees with the human holdase literature: BAG6
      preferentially captures aggregation-prone hydrophobic or misfolded clients during
      quality control.'
    action: ACCEPT
    reason: This matches the experimentally supported BAG6 holdase role in ERAD and
      mislocalized-protein triage.
    supported_by:
    - reference_id: PMID:21636303
    - reference_id: file:human/BAG6/BAG6-notes.md
- term:
    id: GO:0071818
    label: BAT3 complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: The phylogenetic BAT3 complex annotation agrees with multiple human studies
      placing BAG6 in a heterotrimeric BAG6/UBL4A/GET4(TRC35) complex.
    action: ACCEPT
    reason: Complex membership is well supported and central to both GET-pathway and
      UPS-adjacent BAG6 functions.
    supported_by:
    - reference_id: PMID:20676083
    - reference_id: PMID:25535373
- term:
    id: GO:0001822
    label: kidney development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Developmental annotations are plausible downstream consequences from
      mammalian loss-of-function studies, but they are not BAG6's core conserved proteostasis
      role.
    action: KEEP_AS_NON_CORE
    reason: Keep as contextual biology rather than a core molecular/process function.
- term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Retain more specific proteostasis terms instead of this umbrella catabolic
      label.
- term:
    id: GO:0007130
    label: synaptonemal complex assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: This reproductive annotation reflects secondary mammalian biology rather
      than BAG6's central proteostasis function.
    action: KEEP_AS_NON_CORE
    reason: Treat as contextual/non-core.
- term:
    id: GO:0007283
    label: spermatogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: This reproductive-process annotation is best treated as contextual because
      BAG6's conserved role is proteostasis triage, not gametogenesis machinery.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0007420
    label: brain development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Any developmental nervous-system consequence is downstream/contextual
      rather than part of BAG6's main evolved role.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0030324
    label: lung development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: This developmental annotation reflects contextual organismal phenotypes
      rather than BAG6's core GET/UPS-boundary biology.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0030544
    label: Hsp70 protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: This looks like over-propagation from BAG family naming. BAG6 is explicitly
      not a canonical BAG-domain Hsp70 nucleotide-exchange factor.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:25535373
    - reference_id: PMID:25713138
    - reference_id: file:human/BAG6/BAG6-notes.md
- term:
    id: GO:0031593
    label: polyubiquitin modification-dependent protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: This broad automated propagation is not well grounded in the direct BAG6
      mechanistic literature.
    action: REMOVE
    reason: The reviewed papers support client triage with E3s and DUBs, not a specific
      polyubiquitin-binding activity.
- term:
    id: GO:0032435
    label: negative regulation of proteasomal ubiquitin-dependent protein catabolic
      process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: This regulatory proteolysis term reflects secondary spermatogenic/HSPA2
      biology rather than BAG6's central proteostasis role.
    action: KEEP_AS_NON_CORE
    reason: Keep as contextual/non-core.
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Apoptosis-related effects exist in some contexts, but this broad automated
      term is not the best summary of BAG6 function.
    action: KEEP_AS_NON_CORE
    reason: Retain only as non-core context.
- term:
    id: GO:0043161
    label: proteasome-mediated ubiquitin-dependent protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: BAG6 contributes to selected proteasomal quality-control routes, but
      this automated term is broader and less informative than the specific BAG6-supported
      processes.
    action: MARK_AS_OVER_ANNOTATED
    reason: Prefer ERAD, tail-anchored insertion, or ER-stress pre-emptive quality
      control terms.
- term:
    id: GO:0045861
    label: negative regulation of proteolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: This negative-regulation term reflects context-specific stabilization
      biology rather than the main BAG6 proteostasis program.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0045995
    label: regulation of embryonic development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Embryonic-development phenotypes are contextual downstream consequences
      and not the core conserved BAG6 role.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Protein stabilization is context-specific for selected partners and not
      the best core descriptor of BAG6.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0070059
    label: intrinsic apoptotic signaling pathway in response to endoplasmic reticulum
      stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ER-stress apoptosis is a context-dependent consequence, not BAG6's principal
      conserved function.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0070628
    label: proteasome binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: The reviewed BAG6 papers place clients en route to the proteasome but
      do not establish a clean direct proteasome-binding activity.
    action: REMOVE
    reason: This term is too specific for the available evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14667819
  review:
    summary: The source interaction is too generic to retain as a useful BAG6 annotation.
    action: REMOVE
    reason: GO:0005515 is uninformative here and BAG6 already has more specific mechanistically
      grounded annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  review:
    summary: The source interaction is too generic to retain as a useful BAG6 annotation.
    action: REMOVE
    reason: GO:0005515 is uninformative here and BAG6 already has more specific mechanistically
      grounded annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18852879
  review:
    summary: The exosome/NK paper supports a contextual receptor-ligand role, not
      a useful standalone generic protein-binding annotation.
    action: REMOVE
    reason: Retain the more specific immune-context terms instead.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21903422
  review:
    summary: This generic interaction term adds no useful BAG6-specific functional
      information.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22046132
  review:
    summary: This generic interaction term adds no useful BAG6-specific functional
      information.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22807449
  review:
    summary: This generic interaction term adds no useful BAG6-specific functional
      information.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25036637
  review:
    summary: This generic interaction term adds no useful BAG6-specific functional
      information.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  review:
    summary: This generic interaction term adds no useful BAG6-specific functional
      information.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  review:
    summary: This generic interaction term adds no useful BAG6-specific functional
      information.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  review:
    summary: This generic interaction term adds no useful BAG6-specific functional
      information.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: This generic interaction term adds no useful BAG6-specific functional
      information.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: This generic interaction term adds no useful BAG6-specific functional
      information.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Extracellular release is real but limited to stress/tumor exosome contexts
      rather than BAG6's main intracellular proteostasis role.
    action: KEEP_AS_NON_CORE
    reason: Keep as contextual, non-core localization.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: BAG6 is a bona fide nucleo-cytoplasmic protein, and nuclear localization
      is repeatedly observed in the literature and UniProt curation.
    action: ACCEPT
    reason: Nuclear localization is real even though the principal PN role is cytosolic.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Cytosolic localization is central to BAG6 GET/ERAD/mislocalized-protein
      triage functions.
    action: ACCEPT
    reason: The core proteostasis role depends on cytosolic BAG6 complex localization.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: Nucleoplasmic signal is compatible with BAG6's documented nuclear pool
      and DNA-damage-associated functions.
    action: ACCEPT
    reason: This is a defensible subnuclear localization.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: Independent localization evidence also places BAG6 in the cytosol.
    action: ACCEPT
    reason: This is fully consistent with the core proteostasis model.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40105103
  review:
    summary: This generic interaction term adds no useful BAG6-specific functional
      information.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0140597
    label: protein carrier chaperone
  evidence_type: IDA
  original_reference_id: PMID:21636303
  review:
    summary: This is one of the strongest BAG6 annotations. The 2011 Mol Cell study
      directly supports a holdase/carrier role for retrotranslocated hydrophobic clients.
    action: ACCEPT
    reason: Bag6 maintains aggregation-prone clients in an unfolded yet soluble state
      and helps deliver them within quality-control pathways.
    supported_by:
    - reference_id: PMID:21636303
    - reference_id: PMID:20676083
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: NAS
  original_reference_id: PMID:25535373
  review:
    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.
    action: ACCEPT
    reason: The BAG6 complex acts in the cytosol before ER insertion or proteasomal
      routing.
- term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  evidence_type: IDA
  original_reference_id: PMID:20676083
  review:
    summary: PMID:20676083 is about ribosome-associated capture and handoff of tail-anchored
      proteins to TRC40, not a generic ubiquitin-dependent catabolic process.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0071816
      label: tail-anchored membrane protein insertion into ER membrane
- term:
    id: GO:0006620
    label: post-translational protein targeting to endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:25535373
  review:
    summary: This matches the PN GET-pathway mapping and the structural/biochemical
      literature on tail-anchor targeting.
    action: ACCEPT
    reason: BAG6 participates in post-translational delivery of tail-anchored proteins
      toward the ER membrane.
    supported_by:
    - reference_id: PMID:25535373
    - reference_id: PMID:20676083
- term:
    id: GO:0031647
    label: regulation of protein stability
  evidence_type: IDA
  original_reference_id: PMID:21636303
  review:
    summary: The paper supports holdase/chaperone behavior rather than a broad generic
      regulation-of-stability process.
    action: MODIFY
    reason: A molecular chaperone/carrier term is a more faithful representation of
      the evidence.
    proposed_replacement_terms:
    - id: GO:0140597
      label: protein carrier chaperone
- term:
    id: GO:0048018
    label: receptor ligand activity
  evidence_type: IDA
  original_reference_id: PMID:18852879
  review:
    summary: Exosomal BAG6 can act as an NKp30 ligand, but this immune signaling role
      is contextual and not the core conserved BAG6 function.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core context.
    supported_by:
    - reference_id: PMID:18852879
    - reference_id: PMID:18055229
- term:
    id: GO:0051132
    label: NK T cell activation
  evidence_type: IDA
  original_reference_id: PMID:18852879
  review:
    summary: The paper concerns NK-cell activation, not NK T-cell activation.
    action: MODIFY
    reason: Replace with natural killer cell activation to match the actual experiment.
    proposed_replacement_terms:
    - id: GO:0030101
      label: natural killer cell activation
- term:
    id: GO:0036503
    label: ERAD pathway
  evidence_type: NAS
  original_reference_id: PMID:21636303
  review:
    summary: Although this is an author statement-level annotation, the underlying
      study directly demonstrates a BAG6 holdase role that improves ERAD efficiency.
    action: ACCEPT
    reason: The evidence supports ERAD pathway participation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25713138
  review:
    summary: The structural paper supports complex architecture and adaptor function,
      not a useful generic protein-binding annotation.
    action: REMOVE
    reason: Retain the specific adaptor/core-complex annotations instead.
- term:
    id: GO:0060090
    label: molecular adaptor activity
  evidence_type: EXP
  original_reference_id: PMID:25713138
  review:
    summary: BAG6 organizes UBL4A and TRC35/GET4 and supports substrate handoff, which
      is well captured by molecular adaptor activity.
    action: ACCEPT
    reason: This term fits BAG6's bridge/scaffold role at the GET-pathway and cytosolic
      quality-control boundary.
    supported_by:
    - reference_id: PMID:25713138
    - reference_id: PMID:25535373
- term:
    id: GO:0140677
    label: molecular function activator activity
  evidence_type: IEP
  original_reference_id: PMID:25713138
  review:
    summary: The cited paper does not establish BAG6 as a direct molecular-function
      activator of another enzyme or receptor.
    action: REMOVE
    reason: This annotation overstates the structural/adaptor evidence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27113755
  review:
    summary: This generic interaction term adds no useful BAG6-specific functional
      information.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0045995
    label: regulation of embryonic development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Orthology-based developmental regulation is plausible but not part of
      BAG6's core proteostasis identity.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core context.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29042515
  review:
    summary: This paper is informative for localization regulation, but GO:0005515
      remains too generic.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:29042515
  review:
    summary: This study directly addresses BAG6 nucleo-cytoplasmic partitioning and
      supports nuclear localization.
    action: ACCEPT
    reason: Nuclear BAG6 is real and regulated by TRC35/GET4 binding.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:29042515
  review:
    summary: This study directly supports cytosolic retention of BAG6 by TRC35/GET4.
    action: ACCEPT
    reason: Cytosolic BAG6 is the state associated with core proteostasis functions.
- term:
    id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
  evidence_type: IDA
  original_reference_id: PMID:25535373
  review:
    summary: The minimal BAG6 complex directly supports transfer of tail-anchored
      substrates into the TRC40/GET pathway.
    action: ACCEPT
    reason: This is core PN-supported biology.
    supported_by:
    - reference_id: PMID:25535373
    - reference_id: PMID:20676083
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26876100
  review:
    summary: This generic interaction term adds no useful BAG6-specific functional
      information.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14960581
  review:
    summary: The ricin paper is informative for apoptosis context, but GO:0005515
      remains too generic.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0061857
    label: endoplasmic reticulum stress-induced pre-emptive quality control
  evidence_type: IMP
  original_reference_id: PMID:26565908
  review:
    summary: This is a specific stress-responsive proteostasis process that the paper
      directly supports.
    action: ACCEPT
    reason: Bag6 contributes to degradation of rerouted ER pre-emptive quality-control
      substrates under ER stress.
    supported_by:
    - reference_id: PMID:26565908
- term:
    id: GO:0010498
    label: proteasomal protein catabolic process
  evidence_type: IMP
  original_reference_id: PMID:26565908
  review:
    summary: The specific process shown in the paper is ER stress-induced pre-emptive
      quality control, not a generic proteasomal catabolic pathway in isolation.
    action: MARK_AS_OVER_ANNOTATED
    reason: Keep the more specific GO:0061857 annotation instead.
- term:
    id: GO:0036503
    label: ERAD pathway
  evidence_type: IMP
  original_reference_id: PMID:26565908
  review:
    summary: PMID:26565908 is about ER stress-induced pre-emptive quality control,
      which is related to but distinct from canonical ERAD.
    action: MODIFY
    reason: Replace with the specific ER pQC term.
    proposed_replacement_terms:
    - id: GO:0061857
      label: endoplasmic reticulum stress-induced pre-emptive quality control
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  review:
    summary: A broad membrane term is too imprecise for BAG6, which is mainly cytosolic/nuclear
      with regulated ER-membrane association in specific QC contexts.
    action: MARK_AS_OVER_ANNOTATED
    reason: If membrane association is retained, it should be ER-membrane-specific
      rather than generic membrane.
- term:
    id: GO:0002429
    label: immune response-activating cell surface receptor signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:18852879
  review:
    summary: This immune signaling annotation is supported in exosome/NK-cell contexts
      but is clearly contextual rather than core BAG6 biology.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
    supported_by:
    - reference_id: PMID:18852879
    - reference_id: PMID:18055229
- term:
    id: GO:0005102
    label: signaling receptor binding
  evidence_type: IPI
  original_reference_id: PMID:18852879
  review:
    summary: The immune paper is better captured by receptor ligand activity than
      a generic signaling receptor binding term.
    action: MODIFY
    reason: Replace with receptor ligand activity.
    proposed_replacement_terms:
    - id: GO:0048018
      label: receptor ligand activity
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:14960581
  review:
    summary: The ricin study also observed nuclear BAG6, consistent with BAG6's established
      nucleo-cytoplasmic distribution.
    action: ACCEPT
    reason: Nuclear localization is defensible.
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:14960581
  review:
    summary: Ricin-induced apoptosis is a real contextual role but not BAG6's core
      conserved proteostasis function.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0030101
    label: natural killer cell activation
  evidence_type: IDA
  original_reference_id: PMID:18852879
  review:
    summary: Natural killer cell activation is experimentally supported for exosomal
      BAG6 but remains a contextual immune role.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
    supported_by:
    - reference_id: PMID:18852879
    - reference_id: PMID:18055229
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: IDA
  original_reference_id: PMID:18852879
  review:
    summary: Exosomal BAG6 is experimentally documented, but this is a conditional
      extracellular context rather than the main cellular location.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core localization.
    supported_by:
    - reference_id: PMID:18852879
- term:
    id: GO:0036503
    label: ERAD pathway
  evidence_type: IDA
  original_reference_id: PMID:23129660
  review:
    summary: This paper studies SGTA antagonism of BAG6-mediated triage of mislocalized
      proteins in the cytosol, not canonical ERAD.
    action: MODIFY
    reason: Replace with the narrower protein-quality-control term that better fits
      cytosolic degradation of mislocalized hydrophobic clients.
    proposed_replacement_terms:
    - id: GO:0006515
      label: protein quality control for misfolded or incompletely synthesized proteins
- term:
    id: GO:0036503
    label: ERAD pathway
  evidence_type: IDA
  original_reference_id: PMID:24981174
  review:
    summary: PMID:24981174 defines RNF126-dependent cytosolic quality control of mislocalized
      proteins rather than general ERAD.
    action: MODIFY
    reason: Replace with the more specific protein-quality-control term rather than
      the broader ubiquitin-dependent catabolic umbrella term.
    proposed_replacement_terms:
    - id: GO:0006515
      label: protein quality control for misfolded or incompletely synthesized proteins
- term:
    id: GO:1904294
    label: positive regulation of ERAD pathway
  evidence_type: IMP
  original_reference_id: PMID:24424410
  review:
    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.
    action: MODIFY
    reason: The direct BAG6 claim is better captured as ERAD pathway participation.
    proposed_replacement_terms:
    - id: GO:0036503
      label: ERAD pathway
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:21636303
  review:
    summary: Whole-cell cytoplasmic localization is fully consistent with the BAG6
      complex's proteostasis role.
    action: ACCEPT
    reason: This is a defensible localization term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25535373
  review:
    summary: The structural complex paper supports specific adaptor/complex roles,
      not generic protein binding.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0071818
    label: BAT3 complex
  evidence_type: IDA
  original_reference_id: PMID:25535373
  review:
    summary: This paper directly analyzes the BAG6 heterotrimeric complex architecture.
    action: ACCEPT
    reason: BAT3 complex membership is well supported.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23246001
  review:
    summary: This ERAD paper supports specific SGTA/BAG6 pathway functions rather
      than a useful generic binding term.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:23246001
  review:
    summary: The SGTA/BAG6 ERAD paper supports a cytosolic BAG6 pool.
    action: ACCEPT
    reason: This matches the core QC role.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:23246001
  review:
    summary: The paper supports regulated ER-membrane association through ERAD machinery
      rather than a generic membrane localization.
    action: MODIFY
    reason: Use endoplasmic reticulum membrane as the more faithful location.
    proposed_replacement_terms:
    - id: GO:0005789
      label: endoplasmic reticulum membrane
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:21636303
  review:
    summary: The 2011 ERAD study notes nuclear sequestration when Trc35 is absent,
      consistent with BAG6's known dynamic localization.
    action: ACCEPT
    reason: Nuclear localization is supported.
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:21636303
  review:
    summary: Bag6 physically associates with ERAD E3 ligases such as gp78/AMFR and
      SYVN1, which is central to its UPS-adjacent chaperone role.
    action: ACCEPT
    reason: This specific binding term is mechanistically informative and supported.
    supported_by:
    - reference_id: PMID:21636303
- term:
    id: GO:0051787
    label: misfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:21636303
  review:
    summary: This is the key direct evidence for BAG6 recognizing aggregation-prone
      hydrophobic/misfolded clients.
    action: ACCEPT
    reason: The term accurately captures BAG6 holdase specificity.
    supported_by:
    - reference_id: PMID:21636303
- term:
    id: GO:0071818
    label: BAT3 complex
  evidence_type: IDA
  original_reference_id: PMID:21636303
  review:
    summary: The paper directly studies the BAG6/Ubl4A/Trc35 complex.
    action: ACCEPT
    reason: Complex membership is well supported.
- term:
    id: GO:1990381
    label: ubiquitin-specific protease binding
  evidence_type: IPI
  original_reference_id: PMID:24424410
  review:
    summary: Direct interaction with USP13 is well supported, but this is a specific
      partner interaction rather than the best core BAG6 function summary.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core mechanistic context.
    supported_by:
    - reference_id: PMID:24424410
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IPI
  original_reference_id: PMID:24981174
  review:
    summary: RNF126 recruitment to the BAG6 UBL domain is a core mechanistic part
      of mislocalized-protein triage.
    action: ACCEPT
    reason: This specific ligase-binding annotation is supported and informative.
    supported_by:
    - reference_id: PMID:24981174
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18765639
  review:
    summary: The chromatin-regulator interaction paper does not justify retaining
      a generic protein-binding term.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0001822
    label: kidney development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Mouse-based developmental evidence is plausible but not core to human
      BAG6 proteostasis biology.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17403783
  review:
    summary: The p53 acetylation paper supports a specific nuclear scaffold role,
      not a useful generic protein-binding annotation.
    action: REMOVE
    reason: Remove generic protein-binding carryover.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17403783
  review:
    summary: This paper supports nuclear BAG6 during DNA-damage signaling.
    action: ACCEPT
    reason: Nuclear localization is well supported.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:17403783
  review:
    summary: This paper also supports the broader nucleo-cytoplasmic distribution
      of BAG6.
    action: ACCEPT
    reason: Cytosolic BAG6 is consistent with its principal proteostasis role.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:20676083
  review:
    summary: The ribosome-associated TA-targeting study places BAG6 complex function
      in the cytosol.
    action: ACCEPT
    reason: Cytosolic localization is central to GET-pathway capture/handoff.
- term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: The broad catabolic-process inference is directionally consistent with
      BAG6 QC biology but loses specificity.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core rather than using it as a core summary term.
- term:
    id: GO:0007130
    label: synaptonemal complex assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Orthology-based reproductive biology is secondary/contextual.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0007283
    label: spermatogenesis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Orthology-based reproductive biology is secondary/contextual.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0007420
    label: brain development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Orthology-based developmental biology is secondary/contextual.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0018393
    label: internal peptidyl-lysine acetylation
  evidence_type: IDA
  original_reference_id: PMID:17403783
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core context.
    supported_by:
    - reference_id: PMID:17403783
- term:
    id: GO:0030324
    label: lung development
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Orthology-based developmental biology is secondary/contextual.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0031593
    label: polyubiquitin modification-dependent protein binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: The BAG6 literature reviewed here does not provide a solid basis for
      a direct polyubiquitin-binding activity.
    action: REMOVE
    reason: Remove this inferred binding term.
- term:
    id: GO:0032435
    label: negative regulation of proteasomal ubiquitin-dependent protein catabolic
      process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: This reflects secondary stabilization biology rather than BAG6's central
      PN role.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0042771
    label: intrinsic apoptotic signaling pathway in response to DNA damage by p53
      class mediator
  evidence_type: IMP
  original_reference_id: PMID:17403783
  review:
    summary: This DNA-damage apoptosis role is well supported but context-specific.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core nuclear stress biology.
    supported_by:
    - reference_id: PMID:17403783
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IDA
  original_reference_id: PMID:20676083
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Keep as mechanistically informative but non-core.
- term:
    id: GO:0045861
    label: negative regulation of proteolysis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Secondary stabilization/proteolysis control is contextual rather than
      core.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Selected-client stabilization is context-specific and not the main BAG6
      role.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0070059
    label: intrinsic apoptotic signaling pathway in response to endoplasmic reticulum
      stress
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ER-stress apoptosis is context-dependent and not BAG6's principal conserved
      function.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core.
- term:
    id: GO:0070628
    label: proteasome binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Direct proteasome binding is not clearly established by the BAG6 papers
      reviewed here.
    action: REMOVE
    reason: Remove the inferred binding term.
- term:
    id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
  evidence_type: IDA
  original_reference_id: PMID:20676083
  review:
    summary: This is the direct GET-pathway core BAG6 process supported by the landmark
      ribosome-associated TA-targeting paper.
    action: ACCEPT
    reason: The evidence specifically fits tail-anchored membrane protein insertion
      into the ER membrane.
    supported_by:
    - reference_id: PMID:20676083
- term:
    id: GO:0071818
    label: BAT3 complex
  evidence_type: IDA
  original_reference_id: PMID:20676083
  review:
    summary: The 2010 Nature study defines the Bat3/Trc35/Ubl4A complex as the relevant
      functional unit.
    action: ACCEPT
    reason: BAT3 complex membership is directly supported.
core_functions:
- molecular_function:
    id: GO:0140597
    label: protein carrier chaperone
  directly_involved_in:
  - id: GO:0036503
    label: ERAD pathway
  - id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
  locations:
  - id: GO:0005829
    label: cytosol
  in_complex:
    id: GO:0071818
    label: BAT3 complex
  description: BAG6 acts as an ATP-independent holdase/carrier for hydrophobic, misfolded,
    retrotranslocated, or tail-anchored client proteins, keeping them soluble long
    enough for productive ER delivery or proteasome-directed quality control.
  supported_by:
  - reference_id: PMID:21636303
  - reference_id: PMID:20676083
  - reference_id: PMID:25535373
- molecular_function:
    id: GO:0060090
    label: molecular adaptor activity
  directly_involved_in:
  - id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
  locations:
  - id: GO:0005829
    label: cytosol
  in_complex:
    id: GO:0071818
    label: BAT3 complex
  description: Within the BAG6/UBL4A/GET4 complex, BAG6 provides the scaffold/adaptor
    surface that links SGTA-bound hydrophobic clients to the TRC40/GET pathway and
    organizes the pretargeting complex architecture.
  supported_by:
  - reference_id: PMID:25535373
  - reference_id: PMID:25713138
- molecular_function:
    id: GO:0051787
    label: misfolded protein binding
  directly_involved_in:
  - id: GO:0036503
    label: ERAD pathway
  - id: GO:0061857
    label: endoplasmic reticulum stress-induced pre-emptive quality control
  locations:
  - id: GO:0005829
    label: cytosol
  in_complex:
    id: GO:0071818
    label: BAT3 complex
  description: BAG6 preferentially recognizes aggregation-prone hydrophobic or misfolded
    clients generated during ERAD, cytosolic mislocalization, or ER stress rerouting,
    linking substrate capture to downstream quality-control decisions.
  supported_by:
  - reference_id: PMID:21636303
  - reference_id: PMID:26565908
status: COMPLETE

Gene Description

Existing Annotations Review

Core Functions

BAG6 acts as an ATP-independent holdase/carrier for hydrophobic, misfolded, retrotranslocated, or tail-anchored client proteins, keeping them soluble long enough for productive ER delivery or proteasome-directed quality control.

Within the BAG6/UBL4A/GET4 complex, BAG6 provides the scaffold/adaptor surface that links SGTA-bound hydrophobic clients to the TRC40/GET pathway and organizes the pretargeting complex architecture.

BAG6 preferentially recognizes aggregation-prone hydrophobic or misfolded clients generated during ERAD, cytosolic mislocalization, or ER stress rerouting, linking substrate capture to downstream quality-control decisions.

References

📚 Additional Documentation

Notes

BAG6 notes

PN framing

Core proteostasis biology

Contextual, non-core roles

📄 View Raw YAML