Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: PFDN6 is a cytoplasmic protein as part of the prefoldin heterohexamer that captures unfolded substrates in the cytoplasm and delivers them to TRiC/CCT. This is well supported by the IBA annotation which is phylogenetically consistent across eukaryotes. UniProt does not specify a subcellular location annotation for PFDN6, but the canonical function of prefoldin as a cytosolic co-chaperone is well established (PMID:9630229). Reason: The cytoplasmic localization is the canonical site of prefoldin function, capturing unfolded actin and tubulin for delivery to TRiC/CCT. The IBA annotation is phylogenetically well supported by data from yeast, plants, worm, and human. Supporting Evidence: PMID:9630229 We describe the discovery of a heterohexameric chaperone protein, prefoldin, based on its ability to capture unfolded actin. Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target proteins to it.
GO:0006457 protein folding	IBA GO_REF:0000033	ACCEPT	Summary: Protein folding is the core biological process in which prefoldin participates, capturing non-native substrates and delivering them to TRiC/CCT for productive folding. The IBA annotation is phylogenetically well supported. PFDN6 as a beta subunit contributes directly to this function through its coiled-coil tentacle that engages unfolded substrates (PMID:9630229, PMID:30955883). Reason: Protein folding is the core biological process of the prefoldin complex. The annotation is at the right level of specificity for the BP axis. More specific terms like chaperone-mediated protein complex assembly are also captured separately. Supporting Evidence: PMID:9630229 prefoldin promotes folding in an environment in which there are many competing pathways for nonnative proteins. PMID:30955883 The supra-chaperone assembly formed by PFD and TRiC is essential to prevent toxic conformations and ensure effective cellular proteostasis.
GO:0016272 prefoldin complex	IBA GO_REF:0000033	ACCEPT	Summary: PFDN6 is one of the four beta subunits of the canonical prefoldin heterohexamer. This is a core localization for the protein, well established from the original discovery (PMID:9630229) through to recent structural studies (PMID:30955883). The IBA annotation is phylogenetically consistent. Reason: Membership in the prefoldin complex is a defining feature of PFDN6. This is supported by multiple lines of experimental evidence as well as phylogenetic inference. Supporting Evidence: PMID:9630229 We describe the discovery of a heterohexameric chaperone protein, prefoldin, based on its ability to capture unfolded actin. PMID:30955883 these hetero-oligomeric chaperones associate in a defined architecture, through a conserved interface of electrostatic contacts
GO:0051087 protein-folding chaperone binding	IBA GO_REF:0000033	ACCEPT	Summary: Prefoldin binds specifically to the TRiC/CCT chaperonin to transfer substrate proteins to it for folding. The interaction between prefoldin and TRiC/CCT is mediated through a conserved electrostatic interface (PMID:30955883). This MF term accurately captures the binding of prefoldin subunits to the downstream chaperonin. Reason: Binding to the TRiC/CCT chaperonin is a core molecular function of prefoldin subunits. The IBA annotation is consistent with experimental data showing prefoldin-TRiC/CCT interaction through a conserved electrostatic interface. Supporting Evidence: PMID:9630229 Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target proteins to it. PMID:30955883 these hetero-oligomeric chaperones associate in a defined architecture, through a conserved interface of electrostatic contacts that serves as a pivot point for a TRiC-PFD conformational cycle.
GO:0051131 chaperone-mediated protein complex assembly	IBA GO_REF:0000033	ACCEPT	Summary: Prefoldin assists in the assembly of cytoskeletal protein complexes by capturing unfolded actin and tubulin monomers and delivering them to TRiC/CCT, which folds them into conformations competent for polymerization and complex assembly. The IBA annotation is consistent with experimental evidence (PMID:9630229). Reason: This term appropriately captures the role of prefoldin in assisting the chaperonin-mediated assembly of cytoskeletal complexes (actin filaments, tubulin heterodimers/microtubules). The IBA annotation is phylogenetically well supported. Supporting Evidence: PMID:9630229 Deletion of the gene encoding a prefoldin subunit in S. cerevisiae results in a phenotype similar to those found when c-cpn is mutated, namely impaired functions of the actin and tubulin-based cytoskeleton.
GO:0006457 protein folding	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation from InterPro domain IPR002777 (PFD_beta-like). This is consistent with the experimentally validated function and the IBA annotation for the same term. While redundant with the IBA and IDA annotations, it is not incorrect. Reason: The IEA mapping from the PFD_beta-like domain to protein folding is appropriate and consistent with the experimentally determined function. Redundancy with other evidence codes is acceptable.
GO:0016272 prefoldin complex	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation from InterPro domain IPR002777 (PFD_beta-like). Consistent with the well-established membership of PFDN6 in the prefoldin complex. Redundant with IBA and IDA annotations but not incorrect. Reason: The IEA mapping from the prefoldin beta domain to prefoldin complex membership is appropriate and consistent with multiple other lines of evidence.
GO:0032991 protein-containing complex	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine-learning-derived annotation placing PFDN6 in a protein-containing complex. While technically correct, this is extremely generic and adds no information beyond what is already captured by the more specific GO:0016272 prefoldin complex annotations. Reason: While overly broad, this IEA annotation is not incorrect. It is subsumed by the more specific prefoldin complex annotation. Keeping it as a broad IEA is acceptable since more informative annotations already exist.
GO:0051082 unfolded protein binding	IEA GO_REF:0000002	MODIFY	Summary: IEA annotation from InterPro domain mapping. While prefoldin does bind unfolded proteins, GO:0051082 "unfolded protein binding" is a molecular function term that describes simple binding to unfolded proteins. The more accurate molecular function for prefoldin is GO:0044183 "protein folding chaperone" which captures the active chaperone role of binding to assist the protein folding process, rather than merely binding unfolded proteins. Reason: Prefoldin does not merely bind unfolded proteins passively; it actively functions as a co-chaperone that captures non-native substrates and delivers them to TRiC/CCT. GO:0044183 "protein folding chaperone" (defined as "Binding to a protein or a protein-containing complex to assist the protein folding process") better describes this active molecular function. Proposed replacements: protein folding chaperone
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: High-throughput binary interactome mapping study (HuRI). PFDN6 interacts with various proteins including MAGEB4, MBD3, CEBPG, FBXO2, KANK2, KIFC3, RPRD1B, AIMP2, and CCHCR1. While these interactions were detected in a systematic screen, protein binding is uninformative as a GO annotation. Reason: Per curation guidelines, GO:0005515 protein binding is uninformative and should be avoided. The high-throughput interactome data does not provide specific enough functional insight to assign a more informative molecular function term. The known functional interactions (with TRiC/CCT, with other prefoldin subunits) are already captured by more specific annotations.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Interactome mapping in context of neurodegenerative disease proteins. PFDN6 interaction with FGFR3 detected. This is a high-throughput study and protein binding is uninformative. Reason: GO:0005515 protein binding is uninformative per curation guidelines. High-throughput interactome mapping does not provide sufficient context for a more specific annotation.
GO:0050821 protein stabilization	NAS PMID:31738558 Upstream ORF-Encoded ASDURF Is a Novel Prefoldin-like Subuni...	ACCEPT	Summary: NAS annotation from ComplexPortal referencing the PAQosome study. PMID:31738558 describes ASDURF as a novel prefoldin-like subunit of the PAQosome and shows that PFDN6 is part of the PAQosome prefoldin-like module. The PAQosome is involved in biogenesis of several protein complexes. While protein stabilization is a downstream consequence of chaperone activity, this annotation is reasonable given the role of prefoldin/PAQosome in preventing aggregation and promoting proper folding. Reason: Protein stabilization is a legitimate downstream consequence of the prefoldin co-chaperone function. The prefoldin complex prevents aggregation of non-native proteins, which constitutes protein stabilization. The NAS evidence from ComplexPortal is appropriately inferred from the PAQosome characterization study. Supporting Evidence: PMID:31738558 The PAQosome is an 11-subunit chaperone involved in the biogenesis of several human protein complexes.
GO:0006457 protein folding	NAS PMID:32699605 The functions and mechanisms of prefoldin complex and prefol...	ACCEPT	Summary: NAS annotation from ComplexPortal, citing a review on prefoldin functions and mechanisms. Consistent with the core function of prefoldin in protein folding. Redundant with IBA and IDA annotations but not incorrect. Reason: The NAS annotation for protein folding is consistent with all other evidence. The review article cited comprehensively describes prefoldin's role in protein folding.
GO:0006457 protein folding	NAS PMID:34761191 A comprehensive analysis of prefoldins and their implication...	ACCEPT	Summary: NAS annotation from ComplexPortal citing Herranz-Montoya et al. 2021 comprehensive analysis of prefoldins. This review describes the canonical prefoldin function as escorting misfolded or non-native proteins to group II chaperonins for folding. Consistent with the core function. Reason: Consistent with the well-established protein folding function of prefoldin. Supporting Evidence: PMID:34761191 several reports indicate they act as co-chaperones escorting misfolded or non-native proteins to group II chaperonins
GO:0050821 protein stabilization	NAS PMID:34761191 A comprehensive analysis of prefoldins and their implication...	ACCEPT	Summary: NAS annotation from ComplexPortal citing Herranz-Montoya et al. 2021 review. Prefoldin prevents aggregation of non-native proteins, which constitutes protein stabilization. This is a legitimate aspect of the prefoldin function. Reason: Protein stabilization through prevention of aggregation is a well-documented aspect of prefoldin function, consistent with the co-chaperone holdase role.
GO:0050821 protein stabilization	NAS PMID:29662061 RPAP3 provides a flexible scaffold for coupling HSP90 to the...	ACCEPT	Summary: NAS annotation from ComplexPortal citing PMID:29662061 (Martino et al. 2018) about RPAP3 coupling HSP90 to the R2TP co-chaperone complex. PFDN6 is part of the PAQosome which includes the R2TP complex and prefoldin-like module. The PAQosome stabilizes client complexes during their assembly, so protein stabilization is a reasonable annotation. Reason: Protein stabilization is an appropriate annotation for PFDN6 as part of the PAQosome, which functions in biogenesis and stabilization of protein complexes. Supporting Evidence: PMID:29662061 RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex.
GO:0006457 protein folding	IDA PMID:30955883 The Chaperonin TRiC/CCT Associates with Prefoldin through a ...	ACCEPT	Summary: IDA annotation from Gestaut et al. 2019 (Cell), which used cryo-EM, crosslinking-mass spectrometry and biochemical approaches to characterize the structural and functional interplay between TRiC/CCT and prefoldin. The study showed that PFD can enhance the rate and yield of the TRiC folding reaction and that disrupting the TRiC-PFD interaction leads to accumulation of amyloid aggregates, demonstrating that the supra-chaperone assembly is essential for effective cellular proteostasis. Reason: Strong experimental evidence from a high-quality Cell paper demonstrating that prefoldin cooperates with TRiC/CCT to promote protein folding and prevent toxic conformations. Supporting Evidence: PMID:30955883 PFD can act after TRiC bound its substrates to enhance the rate and yield of the folding reaction, suppressing non-productive reaction cycles. Disrupting the TRiC-PFD interaction in vivo is strongly deleterious, leading to accumulation of amyloid aggregates.
GO:0016272 prefoldin complex	IDA PMID:30955883 The Chaperonin TRiC/CCT Associates with Prefoldin through a ...	ACCEPT	Summary: IDA annotation from Gestaut et al. 2019, which directly visualized the prefoldin-TRiC complex by cryo-EM, confirming the defined architecture of the prefoldin heterohexamer including PFDN6 as a subunit. Reason: Direct experimental demonstration of PFDN6 as part of the prefoldin complex through cryo-EM structural characterization. Supporting Evidence: PMID:30955883 these hetero-oligomeric chaperones associate in a defined architecture, through a conserved interface of electrostatic contacts
GO:0051082 unfolded protein binding	IDA PMID:30955883 The Chaperonin TRiC/CCT Associates with Prefoldin through a ...	MODIFY	Summary: IDA annotation from Gestaut et al. 2019. The study demonstrated that prefoldin captures unfolded substrates and transfers them to TRiC/CCT. However, the molecular function of prefoldin is better described as GO:0044183 "protein folding chaperone" rather than simple unfolded protein binding, because prefoldin actively assists in the folding process by transferring substrates to TRiC/CCT rather than merely binding unfolded proteins. Reason: The prefoldin complex does not merely bind unfolded proteins; it functions as an active co-chaperone that captures non-native substrates and delivers them to TRiC/CCT. GO:0044183 "protein folding chaperone" better captures this molecular function. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:30955883 PFD alternates between an open "latched" conformation and a closed "engaged" conformation that aligns the PFD-TRiC substrate binding chambers. PFD can act after TRiC bound its substrates to enhance the rate and yield of the folding reaction
GO:0001540 amyloid-beta binding	IDA PMID:23614719 Human prefoldin inhibits amyloid-β (Aβ) fibrillation and con...	KEEP AS NON CORE	Summary: IDA annotation from Sorgjerd et al. 2013 (Biochemistry). The study demonstrated that recombinant human prefoldin (hPFD, the full heterohexameric complex) inhibits amyloid-beta (1-42) fibrillation and induces formation of soluble Abeta oligomers that are less toxic (30-40% less toxic than fibrils or archaeal PFD-formed oligomers). This demonstrates that the prefoldin complex as a whole binds amyloid-beta. However, the annotation is made at the level of individual subunits (PFDN6), whereas the binding is a property of the assembled hexamer complex, not of PFDN6 alone. Reason: The amyloid-beta binding was demonstrated for the assembled prefoldin heterohexamer, not for PFDN6 individually. While technically each subunit participates in the complex that binds Abeta, this is not a core function of the gene product and may represent an in vitro property of the holo-complex rather than a physiological role of the individual subunit. Supporting Evidence: PMID:23614719 we investigated the effect of recombinant human PFD (hPFD) on Aβ(1-42) aggregation in vitro and found that hPFD inhibited Aβ fibrillation and induced formation of soluble Aβ oligomers.
GO:0016272 prefoldin complex	IDA PMID:23614719 Human prefoldin inhibits amyloid-β (Aβ) fibrillation and con...	ACCEPT	Summary: IDA annotation from Sorgjerd et al. 2013. The study used recombinant human prefoldin (assembled as a heterohexamer) demonstrating that PFDN6 is part of the complex. Reason: Consistent with all other evidence for PFDN6 membership in the prefoldin complex. Supporting Evidence: PMID:23614719 Prefoldin (PFD) is a molecular chaperone that prevents aggregation of misfolded proteins.
GO:1905907 negative regulation of amyloid fibril formation	IDA PMID:23614719 Human prefoldin inhibits amyloid-β (Aβ) fibrillation and con...	KEEP AS NON CORE	Summary: IDA annotation from Sorgjerd et al. 2013. The study showed that the full recombinant human prefoldin complex inhibits amyloid-beta fibrillation in vitro, with Abeta oligomers formed in the presence of hPFD being 30-40% less toxic. This is a property of the assembled prefoldin complex, not specific to PFDN6 individually. While interesting, this represents an in vitro observation with the holo-complex rather than a core physiological function of the PFDN6 gene product. Reason: The negative regulation of amyloid fibril formation was demonstrated for the full prefoldin heterohexameric complex in vitro. While potentially relevant to Alzheimer's disease biology, this is not a core evolved function of PFDN6 specifically. The annotation is kept as non-core because the evidence is valid but represents a property of the holo-complex. Supporting Evidence: PMID:23614719 hPFD inhibited Aβ fibrillation and induced formation of soluble Aβ oligomers. Interestingly, cell viability measurements ... showed that Aβ oligomers formed by hPFD were 30-40% less toxic
GO:0016272 prefoldin complex	IDA PMID:9630229 Prefoldin, a chaperone that delivers unfolded proteins to cy...	ACCEPT	Summary: IDA annotation from the seminal Vainberg et al. 1998 (Cell) paper that first described the discovery of prefoldin as a heterohexameric chaperone. PFDN6 was identified as one of the six subunits of this complex. Reason: Foundational experimental evidence from the original discovery of prefoldin. Supporting Evidence: PMID:9630229 We describe the discovery of a heterohexameric chaperone protein, prefoldin, based on its ability to capture unfolded actin.
GO:0051082 unfolded protein binding	NAS PMID:9630229 Prefoldin, a chaperone that delivers unfolded proteins to cy...	MODIFY	Summary: NAS annotation from the original Vainberg et al. 1998 paper. The paper demonstrated that prefoldin captures unfolded actin and delivers it to the chaperonin. However, the molecular function is better described as GO:0044183 "protein folding chaperone" since prefoldin actively assists in folding rather than merely binding unfolded proteins. Reason: The original paper demonstrates that prefoldin's function goes beyond simple unfolded protein binding; it actively captures and transfers substrates to the chaperonin for productive folding. GO:0044183 "protein folding chaperone" is the more appropriate molecular function term. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:9630229 Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target proteins to it ... prefoldin promotes folding in an environment in which there are many competing pathways for nonnative proteins.
GO:0051087 protein-folding chaperone binding	IDA PMID:9630229 Prefoldin, a chaperone that delivers unfolded proteins to cy...	ACCEPT	Summary: IDA annotation from Vainberg et al. 1998. The paper directly demonstrated that prefoldin binds specifically to cytosolic chaperonin (c-CPN/TRiC/CCT) and transfers target proteins to it. This is strong direct experimental evidence for chaperonin binding. Reason: Direct experimental demonstration that prefoldin binds specifically to the cytosolic chaperonin, which is the defining molecular interaction for prefoldin's function. Supporting Evidence: PMID:9630229 Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target proteins to it.
GO:0051131 chaperone-mediated protein complex assembly	IDA PMID:9630229 Prefoldin, a chaperone that delivers unfolded proteins to cy...	ACCEPT	Summary: IDA annotation from Vainberg et al. 1998. The paper showed that deletion of a prefoldin subunit gene in yeast results in impaired functions of the actin and tubulin-based cytoskeleton, demonstrating prefoldin's role in chaperone-mediated assembly of cytoskeletal complexes. Reason: Direct experimental evidence from genetic studies showing that prefoldin is required for proper assembly of cytoskeletal protein complexes. Supporting Evidence: PMID:9630229 Deletion of the gene encoding a prefoldin subunit in S. cerevisiae results in a phenotype similar to those found when c-cpn is mutated, namely impaired functions of the actin and tubulin-based cytoskeleton.
GO:0006457 protein folding	NAS PMID:9630229 Prefoldin, a chaperone that delivers unfolded proteins to cy...	ACCEPT	Summary: NAS annotation from the original Vainberg et al. 1998 paper describing prefoldin's role in protein folding. The paper demonstrated that prefoldin promotes folding by directing target proteins to the chaperonin. Redundant with IDA and IBA annotations but consistent. Reason: Consistent with the well-established protein folding function of prefoldin, supported by the foundational paper. Supporting Evidence: PMID:9630229 we show that by directing target proteins to chaperonin, prefoldin promotes folding in an environment in which there are many competing pathways for nonnative proteins.
GO:0044183 protein folding chaperone	IDA PMID:30955883 The Chaperonin TRiC/CCT Associates with Prefoldin through a ...	NEW	Summary: PFDN6, as a subunit of the prefoldin complex, functions as a protein folding chaperone that captures non-native substrates and delivers them to TRiC/CCT. This molecular function term is more appropriate than GO:0051082 "unfolded protein binding" because it captures the active co-chaperone role rather than passive binding. Gestaut et al. 2019 demonstrated that prefoldin alternates between conformations to align substrate binding chambers with TRiC/CCT and enhances the rate and yield of the folding reaction (PMID:30955883). Reason: GO:0044183 "protein folding chaperone" is the most appropriate molecular function term for prefoldin subunits. It is defined as "Binding to a protein or a protein-containing complex to assist the protein folding process" which exactly matches prefoldin's function. This annotation should replace the existing GO:0051082 annotations. Supporting Evidence: PMID:30955883 PFD alternates between an open "latched" conformation and a closed "engaged" conformation that aligns the PFD-TRiC substrate binding chambers. PFD can act after TRiC bound its substrates to enhance the rate and yield of the folding reaction, suppressing non-productive reaction cycles. PMID:9630229 Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target proteins to it ... prefoldin promotes folding in an environment in which there are many competing pathways for nonnative proteins.

Core Functions

PFDN6 is a beta-type subunit of the heterohexameric prefoldin co-chaperone complex that captures unfolded nascent polypeptides (primarily actin and tubulin) and delivers them to the TRiC/CCT chaperonin for ATP-dependent folding. PFDN6 contributes a coiled-coil tentacle with hydrophobic residues that engages exposed hydrophobic patches on non-native substrates. Deletion of prefoldin subunit genes impairs actin and tubulin cytoskeleton function.

Molecular Function:

protein folding chaperone

Directly Involved In:

protein folding chaperone-mediated protein complex assembly

Cellular Locations:

cytoplasm

In Complex:

prefoldin complex

Supporting Evidence:

PMID:9630229
We describe the discovery of a heterohexameric chaperone protein, prefoldin, based on its ability to capture unfolded actin. Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target proteins to it.
PMID:30955883
PFD can act after TRiC bound its substrates to enhance the rate and yield of the folding reaction, suppressing non-productive reaction cycles.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

PMID:23614719

Human prefoldin inhibits amyloid-β (Aβ) fibrillation and contributes to formation of nontoxic Aβ aggregates.

PMID:29662061

RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex.

PMID:30955883

The Chaperonin TRiC/CCT Associates with Prefoldin through a Conserved Electrostatic Interface Essential for Cellular Proteostasis.

PMID:31738558

Upstream ORF-Encoded ASDURF Is a Novel Prefoldin-like Subunit of the PAQosome.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32699605

The functions and mechanisms of prefoldin complex and prefoldin-subunits.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

PMID:34761191

A comprehensive analysis of prefoldins and their implication in cancer.

PMID:9630229

Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin.

📚 Additional Documentation

Deep Research Falcon

(PFDN6-deep-research-falcon.md)

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gene_id: PFDN6
gene_symbol: PFDN6
uniprot_accession: O15212
protein_description: 'RecName: Full=Prefoldin subunit 6; AltName: Full=Protein Ke2;'
gene_info: Name=PFDN6; Synonyms=HKE2, PFD6;
organism_full: Homo sapiens (Human).
protein_family: Belongs to the prefoldin subunit beta family.
protein_domains: PFD_beta-like. (IPR002777); Prefoldin. (IPR009053); Prefoldin_2
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: O15212
Protein Description: RecName: Full=Prefoldin subunit 6; AltName: Full=Protein Ke2;
Gene Information: Name=PFDN6; Synonyms=HKE2, PFD6;
Organism (full): Homo sapiens (Human).
Protein Family: Belongs to the prefoldin subunit beta family.
Key Domains: PFD_beta-like. (IPR002777); Prefoldin. (IPR009053); Prefoldin_2 (PF01920)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "PFDN6" matches the protein description above
Verify the organism is correct: Homo sapiens (Human).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'PFDN6' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene PFDN6 (gene ID: PFDN6, UniProt: O15212) in human.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: O15212
Protein Description: RecName: Full=Prefoldin subunit 6; AltName: Full=Protein Ke2;
Gene Information: Name=PFDN6; Synonyms=HKE2, PFD6;
Organism (full): Homo sapiens (Human).
Protein Family: Belongs to the prefoldin subunit beta family.
Key Domains: PFD_beta-like. (IPR002777); Prefoldin. (IPR009053); Prefoldin_2 (PF01920)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "PFDN6" matches the protein description above
Verify the organism is correct: Homo sapiens (Human).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene PFDN6 (gene ID: PFDN6, UniProt: O15212) in human.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Plan status: Identity verification completed. Literature gathered and synthesized from recent structural, mechanistic, and disease-focused sources (2020–2024). A compact source table is embedded for quick reference to URLs and publication dates.

Key concepts and definitions (current understanding)
- Gene/protein identity and family: PFDN6 (UniProt O15212) encodes prefoldin subunit 6, a beta-class subunit of the canonical eukaryotic prefoldin complex (PFDN1–6). Prefoldin is a conserved heterohexamer (2 alpha + 4 beta subunits) with a jellyfish-like architecture of coiled-coil “tentacles” that capture non-native polypeptides via hydrophobic distal tips; PFDN6 is one of the four beta subunits in this assembly (clockwise subunit order models place PFDN6 between PFDN5 and PFDN4). Canonical function is to escort nascent cytoskeletal clients (actin/tubulin) to the group II chaperonin TRiC/CCT for ATP-driven folding (i.e., a co-chaperone “holdase” and substrate-delivery role) (herranzmontoya2021acomprehensiveanalysis pages 1-2, herranzmontoya2021acomprehensiveanalysis pages 2-4, herranzmontoya2021acomprehensiveanalysis pages 4-5, liang2020thefunctionsand pages 1-2, tahmaz2022prefoldinfunctionin pages 1-2).
- Relationship to TRiC/CCT: Prefoldin binds unstructured clients and interfaces with TRiC/CCT to transfer clients into the open TRiC chamber, facilitating productive engagement with the chaperonin for folding to native state. This division of labor—ATP-independent capture/transfer (prefoldin) and ATP-dependent folding (TRiC)—is a central paradigm in eukaryotic cytosolic proteostasis (gestaut2023structuralvisualizationof pages 1-3, liang2020thefunctionsand pages 1-2, herranzmontoya2021acomprehensiveanalysis pages 1-2).

Structural features and domains
- Subunit/complex architecture: Beta-class prefoldin subunits (including PFDN6) share the PFD_beta-like fold, contributing one coiled-coil “tentacle” bearing hydrophobic residues near the tip to engage exposed hydrophobic patches on non-native substrates. The assembled heterohexamer presents six tentacles surrounding a double beta-barrel hub; flexible tentacles underpin broad client capture and hand-off to TRiC/CCT (liang2020thefunctionsand pages 1-2, herranzmontoya2021acomprehensiveanalysis pages 1-2, herranzmontoya2021acomprehensiveanalysis pages 4-5).
- Client transfer mechanism (recent mechanistic detail): Cryo-EM visualization of human TRiC folding of tubulin captured progressive client states in the TRiC chamber, consistent with upstream prefoldin hand-off into an open ring followed by ATP-driven closure and domain-wise maturation of tubulin; electrostatic interactions and dynamic CCT tails stabilize intermediates on the path to native tubulin (Cell, Apr 2023) (gestaut2023structuralvisualizationof pages 1-3).

Cellular localization and nuclear functions
- Cytosol and nucleus: While the canonical role is cytosolic client capture/transfer, prefoldin subunits (including beta subunits) exhibit nucleo-cytoplasmic distribution and have non-canonical nuclear roles. Reported functions include transcriptional regulation and links to proteasome-dependent protein turnover, indicating that prefoldin contributes to protein homeostasis beyond cytoskeletal folding (review synthesis) (tahmaz2022prefoldinfunctionin pages 1-2).

Experimentally supported clients and pathways
- Cytoskeletal clients and TRiC pathway: Actin and tubulin are obligate clients of TRiC/CCT; prefoldin captures these nascent chains and promotes their efficient delivery and folding. Recent structural work resolved multiple tubulin folding intermediates inside TRiC, consistent with prefoldin-to-TRiC hand-off and a hierarchical folding trajectory driven by TRiC’s ATPase cycle (gestaut2023structuralvisualizationof pages 1-3, liang2020thefunctionsand pages 1-2, herranzmontoya2021acomprehensiveanalysis pages 1-2).
- Broader proteostasis context: Reviews synthesize additional client/process connections for the prefoldin network, including protection from aggregation and participation in protein quality control, with individual subunits exhibiting specialized or independent functions within and beyond the hexamer (tahmaz2022prefoldinfunctionin pages 1-2, herranzmontoya2021acomprehensiveanalysis pages 1-2).

Recent developments (2023–2024; prioritized) and quantitative data
- Structural mechanism of prefoldin–TRiC cooperation (2023): High-resolution cryo-EM of human TRiC with tubulin visualizes sequential, domain-resolved folding within the closed chamber, grounded in prior prefoldin hand-off to open TRiC; the study details electrostatic anchoring, client translocation upon ring closure, and roles for CCT C-termini in stabilizing folding nuclei (Cell, Apr 2023; URL above) (gestaut2023structuralvisualizationof pages 1-3).
- Human cancer context for PFDN6 (2024): A colorectal cancer study integrated TCGA (635 tumors vs 51 normal) and immunohistochemistry on 106 CRC vs 96 para-cancer tissues, and performed PFDN6 knockdown in CRC cell lines with downstream transcriptome profiling and migration phenotyping—together supporting a functional contribution of PFDN6 to CRC biology via transcriptional impacts (eGastroenterology, Apr 2024; URL: https://doi.org/10.1136/egastro-2023-100001). Quantitatively, the study reports cohort sizes (TCGA and IHC) and deploys knockdown validation by qRT-PCR and immunoblot prior to phenotypic and transcriptomic assays (xu2024pfdn6contributesto pages 2-3).

Current applications and real-world implementations
- Proteostasis/structural biology: The prefoldin–TRiC paradigm is directly leveraged in structural proteomics workflows to capture endogenous chaperone–client complexes for cryo-EM, enabling visualization of on-pathway folding states in human cells (e.g., tubulin–TRiC structures), which informs targetable interfaces and chaperone-assisted maturation steps relevant to disease-associated proteostasis defects (gestaut2023structuralvisualizationof pages 1-3).
- Cancer biology and biomarker exploration: Integrative analyses and functional perturbations in CRC models place PFDN6 within tumor-associated transcriptional programs, offering a basis for biomarker and mechanistic exploration in oncology cohorts (cohort sizes and modality mix as above) (xu2024pfdn6contributesto pages 2-3).

Expert opinions and analysis from authoritative sources
- Cancer-focused synthesis: A comprehensive analysis positions PFDN6 within the canonical prefoldin complex and notes broader links to a mammalian unconventional prefoldin-like (URI-containing) assembly that connects to transcriptional regulators, suggesting that prefoldin subunits—including PFDN6—may influence nuclear gene expression programs in addition to cytosolic folding (iScience, Nov 2021; URL: https://doi.org/10.1016/j.isci.2021.103273) (herranzmontoya2021acomprehensiveanalysis pages 2-4, herranzmontoya2021acomprehensiveanalysis pages 8-10, herranzmontoya2021acomprehensiveanalysis pages 4-5).
- Proteostasis review: A 2022 review outlines prefoldin’s ATP-independent holdase and client-transfer roles to TRiC, its nucleo-cytoplasmic localization, and its participation in protein quality control and disease processes, highlighting that individual subunits can have functions independent of the holo-hexamer (Frontiers in Cell and Developmental Biology, Jan 2022; URL: https://doi.org/10.3389/fcell.2021.816214) (tahmaz2022prefoldinfunctionin pages 1-2).

Disease associations and PFDN6-specific links
- Colorectal cancer: In human CRC, PFDN6 was studied using large-scale datasets (TCGA), tissue immunohistochemistry, and perturbation assays in multiple CRC cell lines, with transcriptome profiling following PFDN6 knockdown—together supporting a role for PFDN6 in CRC-associated transcriptional regulation and cell behavior (eGastroenterology, Apr 2024; URL: https://doi.org/10.1136/egastro-2023-100001) (xu2024pfdn6contributesto pages 2-3).
- Additional disease contexts (reviewed): Prefoldin subunits—beta subunits included—have been implicated broadly in cancer and proteostasis disorders; reviews note individual subunit associations with disease phenotypes and stress responses (herranzmontoya2021acomprehensiveanalysis pages 1-2, tahmaz2022prefoldinfunctionin pages 1-2). While these reviews summarize connections, direct human PFDN6-specific mechanistic disease studies remain comparatively limited and are emerging.

Mechanistic pathway placement for PFDN6
- Primary role: PFDN6 functions as one beta subunit in the canonical prefoldin hexamer that captures non-native clients (e.g., nascent actin/tubulin) and delivers them to TRiC/CCT. This places PFDN6 squarely in the cytosolic chaperone network upstream of TRiC, modulating proteostasis and cytoskeletal biogenesis (liang2020thefunctionsand pages 1-2, gestaut2023structuralvisualizationof pages 1-3, herranzmontoya2021acomprehensiveanalysis pages 1-2).
- Non-canonical nuclear contributions (inferred from complex-level evidence): Prefoldin subunits can localize to the nucleus and influence gene expression and protein quality control pathways, suggesting that PFDN6, as part of the holo-complex, may contribute to transcription-related processes described for prefoldin in human cells (review evidence) (tahmaz2022prefoldinfunctionin pages 1-2, herranzmontoya2021acomprehensiveanalysis pages 1-2).

Relevant statistics and data from recent studies
- Cryo-EM structural series (Cell 2023): Multiple near-atomic structures of human TRiC with tubulin across its ATPase cycle resolved client positions, contacts, and folding progression, delineating a stepwise pathway from open-state client engagement (consistent with prefoldin hand-off) to closed-state near-native tubulin (publication date Apr 2023; URL above) (gestaut2023structuralvisualizationof pages 1-3).
- CRC cohorts and assays (eGastroenterology 2024): TCGA cohort size 635 tumors vs 51 normal; IHC on 106 CRC vs 96 para-cancer tissues; functional PFDN6 knockdown in RKO and HCT-116 followed by transcriptome profiling and migration assays, establishing experimental links between PFDN6 perturbation and CRC cell phenotypes (publication date Apr 2024; URL above) (xu2024pfdn6contributesto pages 2-3).

Verification of ambiguity and alignment with UniProt context
- The gene symbol “PFDN6” unambiguously corresponds to human prefoldin subunit 6 (beta family) within the canonical prefoldin heterohexamer, consistent with the provided UniProt accession O15212 and domain/family annotations (PFD_beta-like, Prefoldin). Literature cited above consistently treats PFDN6 as a human prefoldin beta subunit; no conflicting organismal/gene symbol usage was found in the gathered evidence (herranzmontoya2021acomprehensiveanalysis pages 1-2, liang2020thefunctionsand pages 1-2).

Embedded source table
| Year | Reference (journal) | Focus/relevance to PFDN6 | URL |
|---|---|---|---|
| 2024 | Xu F. et al., eGastroenterology | PFDN6 upregulation in colorectal cancer; IHC/TCGA analysis and knockdown phenotypes linking PFDN6 to transcriptional regulation of CRC (xu2024pfdn6contributesto pages 2-3) | https://doi.org/10.1136/egastro-2023-100001 |
| 2023 | Gestaut D. et al., Cell | Cryo-EM visualization of TRiC-mediated tubulin folding showing prefoldin hand-off and mechanistic details of prefoldin→TRiC substrate delivery (gestaut2023structuralvisualizationof pages 1-3) | https://doi.org/10.1016/j.cell.2023.04.004 |
| 2021 | Payán-Bravo L. et al., Nucleic Acids Research | Human prefoldin binds chromatin and modulates RNA Pol II Ser2 phosphorylation and co-transcriptional splicing (related nuclear functions summarized here) (herranzmontoya2021acomprehensiveanalysis pages 2-4) | https://doi.org/10.1101/2020.06.14.150466 |
| 2018 | Banks C.A.S. et al., Scientific Reports | Prefoldin/CCT involvement in HDAC1/2 complex assembly and evidence for nuclear processing roles of prefoldin pathway (herranzmontoya2021acomprehensiveanalysis pages 2-4) | https://doi.org/10.1038/s41598-018-32009-w |
| 2021 | Herranz-Montoya I. et al., iScience | Canonical prefoldin architecture; PFDN6 as a beta-class subunit; links to UPC/URI prefoldin-like assemblies and cancer relevance (herranzmontoya2021acomprehensiveanalysis pages 2-4, herranzmontoya2021acomprehensiveanalysis pages 8-10) | https://doi.org/10.1016/j.isci.2021.103273 |
| 2022 | Tahmaz I. et al., Frontiers in Cell Dev. Biol. | Review of prefoldin function in proteostasis and human disease; discusses individual subunit roles and reported disease links for PFDN6 (tahmaz2022prefoldinfunctionin pages 1-2) | https://doi.org/10.3389/fcell.2021.816214 |
| 2020 | Liang J. et al., Cell & Bioscience | Structural description of prefoldin ("jellyfish" heterohexamer), beta-subunit features and substrate-binding tentacles relevant to PFDN6 function (liang2020thefunctionsand pages 1-2) | https://doi.org/10.1186/s13578-020-00446-8 |

Table: Compact summary table of authoritative references (2020–2024) about human PFDN6/prefoldin, indicating each paper's focus on PFDN6 function, structure, nuclear roles, prefoldin–TRiC cooperation, or disease relevance, with DOI URLs and context citations for traceability.

Conclusions and outstanding questions
- PFDN6 is a core beta subunit of the canonical prefoldin co-chaperone that captures non-native substrates and delivers them to TRiC/CCT for folding; this role is supported by structural and mechanistic advances that visualize client maturation inside human TRiC (2023). The complex-level evidence indicates nucleo-cytoplasmic distribution and contributions to transcriptional regulation and proteostasis beyond cytoskeletal folding. Recent oncology data (2024) place PFDN6 within CRC-associated transcriptional programs with supporting multi-cohort and perturbation evidence, though additional PFDN6-specific mechanistic dissection in human disease is warranted to define causal roles and therapeutic leverage points (gestaut2023structuralvisualizationof pages 1-3, tahmaz2022prefoldinfunctionin pages 1-2, xu2024pfdn6contributesto pages 2-3, herranzmontoya2021acomprehensiveanalysis pages 1-2, liang2020thefunctionsand pages 1-2).

References (URLs and publication dates embedded above via citations)

References

(herranzmontoya2021acomprehensiveanalysis pages 1-2): Irene Herranz-Montoya, Solip Park, and Nabil Djouder. A comprehensive analysis of prefoldins and their implication in cancer. iScience, 24:103273, Nov 2021. URL: https://doi.org/10.1016/j.isci.2021.103273, doi:10.1016/j.isci.2021.103273. This article has 24 citations and is from a peer-reviewed journal.
(herranzmontoya2021acomprehensiveanalysis pages 2-4): Irene Herranz-Montoya, Solip Park, and Nabil Djouder. A comprehensive analysis of prefoldins and their implication in cancer. iScience, 24:103273, Nov 2021. URL: https://doi.org/10.1016/j.isci.2021.103273, doi:10.1016/j.isci.2021.103273. This article has 24 citations and is from a peer-reviewed journal.
(herranzmontoya2021acomprehensiveanalysis pages 4-5): Irene Herranz-Montoya, Solip Park, and Nabil Djouder. A comprehensive analysis of prefoldins and their implication in cancer. iScience, 24:103273, Nov 2021. URL: https://doi.org/10.1016/j.isci.2021.103273, doi:10.1016/j.isci.2021.103273. This article has 24 citations and is from a peer-reviewed journal.
(liang2020thefunctionsand pages 1-2): Jiaxin Liang, Longzheng Xia, Linda Oyang, Jinguan Lin, Shiming Tan, Pin Yi, Yaqian Han, Xia Luo, Hui Wang, Lu Tang, Qing Pan, Yutong Tian, Shan Rao, Min Su, Yingrui Shi, Deliang Cao, Yujuan Zhou, and Qianjin Liao. The functions and mechanisms of prefoldin complex and prefoldin-subunits. Cell & Bioscience, Jul 2020. URL: https://doi.org/10.1186/s13578-020-00446-8, doi:10.1186/s13578-020-00446-8. This article has 70 citations and is from a peer-reviewed journal.
(tahmaz2022prefoldinfunctionin pages 1-2): Ismail Tahmaz, Somayeh Shahmoradi Ghahe, and Ulrike Topf. Prefoldin function in cellular protein homeostasis and human diseases. Frontiers in Cell and Developmental Biology, Jan 2022. URL: https://doi.org/10.3389/fcell.2021.816214, doi:10.3389/fcell.2021.816214. This article has 48 citations and is from a poor quality or predatory journal.
(gestaut2023structuralvisualizationof pages 1-3): Daniel Gestaut, Yanyan Zhao, Junsun Park, Boxue Ma, Alexander Leitner, Miranda Collier, Grigore Pintilie, Soung-Hun Roh, Wah Chiu, and Judith Frydman. Structural visualization of the tubulin folding pathway directed by human chaperonin tric/cct. Cell, 186:2038, Apr 2023. URL: https://doi.org/10.1016/j.cell.2023.04.004, doi:10.1016/j.cell.2023.04.004. This article has 73 citations and is from a highest quality peer-reviewed journal.
(xu2024pfdn6contributesto pages 2-3): Fenghua Xu, Lingyang Kong, Xiao Sun, Wen-Xiang Hui, Lan Jiang, Wenxin Han, Zhifeng Xiao, Ning Li, Dong-feng Chen, Nan Zheng, Jing Han, and Lei Liu. Pfdn6 contributes to colorectal cancer progression via transcriptional regulation. eGastroenterology, 2:e100001, Apr 2024. URL: https://doi.org/10.1136/egastro-2023-100001, doi:10.1136/egastro-2023-100001. This article has 0 citations and is from a peer-reviewed journal.
(herranzmontoya2021acomprehensiveanalysis pages 8-10): Irene Herranz-Montoya, Solip Park, and Nabil Djouder. A comprehensive analysis of prefoldins and their implication in cancer. iScience, 24:103273, Nov 2021. URL: https://doi.org/10.1016/j.isci.2021.103273, doi:10.1016/j.isci.2021.103273. This article has 24 citations and is from a peer-reviewed journal.

Citations

gestaut2023structuralvisualizationof pages 1-3
tahmaz2022prefoldinfunctionin pages 1-2
herranzmontoya2021acomprehensiveanalysis pages 2-4
liang2020thefunctionsand pages 1-2
herranzmontoya2021acomprehensiveanalysis pages 1-2
herranzmontoya2021acomprehensiveanalysis pages 4-5
herranzmontoya2021acomprehensiveanalysis pages 8-10
https://doi.org/10.1136/egastro-2023-100001
https://doi.org/10.1016/j.isci.2021.103273
https://doi.org/10.3389/fcell.2021.816214
https://doi.org/10.1016/j.cell.2023.04.004
https://doi.org/10.1101/2020.06.14.150466
https://doi.org/10.1038/s41598-018-32009-w
https://doi.org/10.1186/s13578-020-00446-8
https://doi.org/10.1016/j.isci.2021.103273,
https://doi.org/10.1186/s13578-020-00446-8,
https://doi.org/10.3389/fcell.2021.816214,
https://doi.org/10.1016/j.cell.2023.04.004,
https://doi.org/10.1136/egastro-2023-100001,

📄 View Raw YAML

id: O15212
gene_symbol: PFDN6
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  PFDN6 encodes prefoldin subunit 6, a beta-class subunit of the canonical heterohexameric prefoldin
  co-chaperone complex (2 alpha + 4 beta subunits). The prefoldin complex captures non-native/unfolded
  polypeptides, particularly nascent actin and tubulin, and delivers them to the TRiC/CCT chaperonin
  for ATP-dependent folding. PFDN6 contributes one coiled-coil tentacle bearing hydrophobic residues
  at its tip to engage exposed hydrophobic patches on non-native substrates. PFDN6 is also a component
  of the PAQosome (prefoldin-like module containing URI1, PFDN2, PFDN6, PDRG1, UXT, and ASDURF), which
  is involved in the biogenesis of several protein complexes. The protein localizes primarily to the
  cytoplasm. Beyond its canonical co-chaperone role, prefoldin subunits have been reported to exhibit
  nuclear functions related to transcriptional regulation, and recent work has linked PFDN6 upregulation
  to colorectal cancer biology.
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PFDN6 is a cytoplasmic protein as part of the prefoldin heterohexamer that captures unfolded
      substrates in the cytoplasm and delivers them to TRiC/CCT. This is well supported by the
      IBA annotation which is phylogenetically consistent across eukaryotes. UniProt does not specify
      a subcellular location annotation for PFDN6, but the canonical function of prefoldin as a
      cytosolic co-chaperone is well established (PMID:9630229).
    action: ACCEPT
    reason: >-
      The cytoplasmic localization is the canonical site of prefoldin function, capturing unfolded
      actin and tubulin for delivery to TRiC/CCT. The IBA annotation is phylogenetically well supported
      by data from yeast, plants, worm, and human.
    supported_by:
      - reference_id: PMID:9630229
        supporting_text: >-
          We describe the discovery of a heterohexameric chaperone protein, prefoldin,
          based on its ability to capture unfolded actin. Prefoldin binds specifically to
          cytosolic chaperonin (c-cpn) and transfers target proteins to it.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Protein folding is the core biological process in which prefoldin participates, capturing
      non-native substrates and delivering them to TRiC/CCT for productive folding. The IBA
      annotation is phylogenetically well supported. PFDN6 as a beta subunit contributes directly
      to this function through its coiled-coil tentacle that engages unfolded substrates (PMID:9630229,
      PMID:30955883).
    action: ACCEPT
    reason: >-
      Protein folding is the core biological process of the prefoldin complex. The annotation is at
      the right level of specificity for the BP axis. More specific terms like chaperone-mediated
      protein complex assembly are also captured separately.
    supported_by:
      - reference_id: PMID:9630229
        supporting_text: >-
          prefoldin promotes folding in an environment in which there are many competing
          pathways for nonnative proteins.
      - reference_id: PMID:30955883
        supporting_text: >-
          The supra-chaperone assembly formed by PFD and TRiC is essential to prevent toxic
          conformations and ensure effective cellular proteostasis.
- term:
    id: GO:0016272
    label: prefoldin complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PFDN6 is one of the four beta subunits of the canonical prefoldin heterohexamer. This is
      a core localization for the protein, well established from the original discovery (PMID:9630229)
      through to recent structural studies (PMID:30955883). The IBA annotation is phylogenetically
      consistent.
    action: ACCEPT
    reason: >-
      Membership in the prefoldin complex is a defining feature of PFDN6. This is supported by
      multiple lines of experimental evidence as well as phylogenetic inference.
    supported_by:
      - reference_id: PMID:9630229
        supporting_text: >-
          We describe the discovery of a heterohexameric chaperone protein, prefoldin,
          based on its ability to capture unfolded actin.
      - reference_id: PMID:30955883
        supporting_text: >-
          these hetero-oligomeric chaperones associate in a defined architecture, through
          a conserved interface of electrostatic contacts
- term:
    id: GO:0051087
    label: protein-folding chaperone binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Prefoldin binds specifically to the TRiC/CCT chaperonin to transfer substrate proteins
      to it for folding. The interaction between prefoldin and TRiC/CCT is mediated through a
      conserved electrostatic interface (PMID:30955883). This MF term accurately captures the
      binding of prefoldin subunits to the downstream chaperonin.
    action: ACCEPT
    reason: >-
      Binding to the TRiC/CCT chaperonin is a core molecular function of prefoldin subunits.
      The IBA annotation is consistent with experimental data showing prefoldin-TRiC/CCT
      interaction through a conserved electrostatic interface.
    supported_by:
      - reference_id: PMID:9630229
        supporting_text: >-
          Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target
          proteins to it.
      - reference_id: PMID:30955883
        supporting_text: >-
          these hetero-oligomeric chaperones associate in a defined architecture, through
          a conserved interface of electrostatic contacts that serves as a pivot point for
          a TRiC-PFD conformational cycle.
- term:
    id: GO:0051131
    label: chaperone-mediated protein complex assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Prefoldin assists in the assembly of cytoskeletal protein complexes by capturing
      unfolded actin and tubulin monomers and delivering them to TRiC/CCT, which folds them
      into conformations competent for polymerization and complex assembly. The IBA annotation
      is consistent with experimental evidence (PMID:9630229).
    action: ACCEPT
    reason: >-
      This term appropriately captures the role of prefoldin in assisting the chaperonin-mediated
      assembly of cytoskeletal complexes (actin filaments, tubulin heterodimers/microtubules).
      The IBA annotation is phylogenetically well supported.
    supported_by:
      - reference_id: PMID:9630229
        supporting_text: >-
          Deletion of the gene encoding a prefoldin subunit in S. cerevisiae results in a
          phenotype similar to those found when c-cpn is mutated, namely impaired functions
          of the actin and tubulin-based cytoskeleton.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation from InterPro domain IPR002777 (PFD_beta-like). This is consistent with the
      experimentally validated function and the IBA annotation for the same term. While redundant
      with the IBA and IDA annotations, it is not incorrect.
    action: ACCEPT
    reason: >-
      The IEA mapping from the PFD_beta-like domain to protein folding is appropriate and consistent
      with the experimentally determined function. Redundancy with other evidence codes is acceptable.
- term:
    id: GO:0016272
    label: prefoldin complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation from InterPro domain IPR002777 (PFD_beta-like). Consistent with the well-established
      membership of PFDN6 in the prefoldin complex. Redundant with IBA and IDA annotations but not incorrect.
    action: ACCEPT
    reason: >-
      The IEA mapping from the prefoldin beta domain to prefoldin complex membership is appropriate
      and consistent with multiple other lines of evidence.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      ARBA machine-learning-derived annotation placing PFDN6 in a protein-containing complex.
      While technically correct, this is extremely generic and adds no information beyond what
      is already captured by the more specific GO:0016272 prefoldin complex annotations.
    action: ACCEPT
    reason: >-
      While overly broad, this IEA annotation is not incorrect. It is subsumed by the more specific
      prefoldin complex annotation. Keeping it as a broad IEA is acceptable since more informative
      annotations already exist.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation from InterPro domain mapping. While prefoldin does bind unfolded proteins,
      GO:0051082 "unfolded protein binding" is a molecular function term that describes simple
      binding to unfolded proteins. The more accurate molecular function for prefoldin is
      GO:0044183 "protein folding chaperone" which captures the active chaperone role of binding
      to assist the protein folding process, rather than merely binding unfolded proteins.
    action: MODIFY
    reason: >-
      Prefoldin does not merely bind unfolded proteins passively; it actively functions as a
      co-chaperone that captures non-native substrates and delivers them to TRiC/CCT.
      GO:0044183 "protein folding chaperone" (defined as "Binding to a protein or a
      protein-containing complex to assist the protein folding process") better describes
      this active molecular function.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: >-
      High-throughput binary interactome mapping study (HuRI). PFDN6 interacts with various
      proteins including MAGEB4, MBD3, CEBPG, FBXO2, KANK2, KIFC3, RPRD1B, AIMP2, and CCHCR1.
      While these interactions were detected in a systematic screen, protein binding is
      uninformative as a GO annotation.
    action: REMOVE
    reason: >-
      Per curation guidelines, GO:0005515 protein binding is uninformative and should be avoided.
      The high-throughput interactome data does not provide specific enough functional insight to
      assign a more informative molecular function term. The known functional interactions
      (with TRiC/CCT, with other prefoldin subunits) are already captured by more specific annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: >-
      Interactome mapping in context of neurodegenerative disease proteins. PFDN6 interaction
      with FGFR3 detected. This is a high-throughput study and protein binding is uninformative.
    action: REMOVE
    reason: >-
      GO:0005515 protein binding is uninformative per curation guidelines. High-throughput
      interactome mapping does not provide sufficient context for a more specific annotation.
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: NAS
  original_reference_id: PMID:31738558
  review:
    summary: >-
      NAS annotation from ComplexPortal referencing the PAQosome study. PMID:31738558 describes
      ASDURF as a novel prefoldin-like subunit of the PAQosome and shows that PFDN6 is part of
      the PAQosome prefoldin-like module. The PAQosome is involved in biogenesis of several protein
      complexes. While protein stabilization is a downstream consequence of chaperone activity,
      this annotation is reasonable given the role of prefoldin/PAQosome in preventing
      aggregation and promoting proper folding.
    action: ACCEPT
    reason: >-
      Protein stabilization is a legitimate downstream consequence of the prefoldin co-chaperone
      function. The prefoldin complex prevents aggregation of non-native proteins, which constitutes
      protein stabilization. The NAS evidence from ComplexPortal is appropriately inferred from
      the PAQosome characterization study.
    supported_by:
      - reference_id: PMID:31738558
        supporting_text: >-
          The PAQosome is an 11-subunit chaperone involved in the biogenesis of several
          human protein complexes.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: NAS
  original_reference_id: PMID:32699605
  review:
    summary: >-
      NAS annotation from ComplexPortal, citing a review on prefoldin functions and mechanisms.
      Consistent with the core function of prefoldin in protein folding. Redundant with IBA
      and IDA annotations but not incorrect.
    action: ACCEPT
    reason: >-
      The NAS annotation for protein folding is consistent with all other evidence. The review
      article cited comprehensively describes prefoldin's role in protein folding.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: NAS
  original_reference_id: PMID:34761191
  review:
    summary: >-
      NAS annotation from ComplexPortal citing Herranz-Montoya et al. 2021 comprehensive analysis
      of prefoldins. This review describes the canonical prefoldin function as escorting
      misfolded or non-native proteins to group II chaperonins for folding. Consistent with
      the core function.
    action: ACCEPT
    reason: >-
      Consistent with the well-established protein folding function of prefoldin.
    supported_by:
      - reference_id: PMID:34761191
        supporting_text: >-
          several reports indicate they act as co-chaperones escorting misfolded or non-native
          proteins to group II chaperonins
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: NAS
  original_reference_id: PMID:34761191
  review:
    summary: >-
      NAS annotation from ComplexPortal citing Herranz-Montoya et al. 2021 review. Prefoldin
      prevents aggregation of non-native proteins, which constitutes protein stabilization.
      This is a legitimate aspect of the prefoldin function.
    action: ACCEPT
    reason: >-
      Protein stabilization through prevention of aggregation is a well-documented aspect
      of prefoldin function, consistent with the co-chaperone holdase role.
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: NAS
  original_reference_id: PMID:29662061
  review:
    summary: >-
      NAS annotation from ComplexPortal citing PMID:29662061 (Martino et al. 2018) about RPAP3
      coupling HSP90 to the R2TP co-chaperone complex. PFDN6 is part of the PAQosome which
      includes the R2TP complex and prefoldin-like module. The PAQosome stabilizes client
      complexes during their assembly, so protein stabilization is a reasonable annotation.
    action: ACCEPT
    reason: >-
      Protein stabilization is an appropriate annotation for PFDN6 as part of the PAQosome,
      which functions in biogenesis and stabilization of protein complexes.
    supported_by:
      - reference_id: PMID:29662061
        supporting_text: >-
          RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IDA
  original_reference_id: PMID:30955883
  review:
    summary: >-
      IDA annotation from Gestaut et al. 2019 (Cell), which used cryo-EM, crosslinking-mass
      spectrometry and biochemical approaches to characterize the structural and functional
      interplay between TRiC/CCT and prefoldin. The study showed that PFD can enhance the rate
      and yield of the TRiC folding reaction and that disrupting the TRiC-PFD interaction leads
      to accumulation of amyloid aggregates, demonstrating that the supra-chaperone assembly is
      essential for effective cellular proteostasis.
    action: ACCEPT
    reason: >-
      Strong experimental evidence from a high-quality Cell paper demonstrating that prefoldin
      cooperates with TRiC/CCT to promote protein folding and prevent toxic conformations.
    supported_by:
      - reference_id: PMID:30955883
        supporting_text: >-
          PFD can act after TRiC bound its substrates to enhance the rate and yield of the
          folding reaction, suppressing non-productive reaction cycles. Disrupting the TRiC-PFD
          interaction in vivo is strongly deleterious, leading to accumulation of amyloid aggregates.
- term:
    id: GO:0016272
    label: prefoldin complex
  evidence_type: IDA
  original_reference_id: PMID:30955883
  review:
    summary: >-
      IDA annotation from Gestaut et al. 2019, which directly visualized the prefoldin-TRiC
      complex by cryo-EM, confirming the defined architecture of the prefoldin heterohexamer
      including PFDN6 as a subunit.
    action: ACCEPT
    reason: >-
      Direct experimental demonstration of PFDN6 as part of the prefoldin complex through
      cryo-EM structural characterization.
    supported_by:
      - reference_id: PMID:30955883
        supporting_text: >-
          these hetero-oligomeric chaperones associate in a defined architecture, through
          a conserved interface of electrostatic contacts
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:30955883
  review:
    summary: >-
      IDA annotation from Gestaut et al. 2019. The study demonstrated that prefoldin captures
      unfolded substrates and transfers them to TRiC/CCT. However, the molecular function of
      prefoldin is better described as GO:0044183 "protein folding chaperone" rather than
      simple unfolded protein binding, because prefoldin actively assists in the folding process
      by transferring substrates to TRiC/CCT rather than merely binding unfolded proteins.
    action: MODIFY
    reason: >-
      The prefoldin complex does not merely bind unfolded proteins; it functions as an active
      co-chaperone that captures non-native substrates and delivers them to TRiC/CCT. GO:0044183
      "protein folding chaperone" better captures this molecular function.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
    supported_by:
      - reference_id: PMID:30955883
        supporting_text: >-
          PFD alternates between an open "latched" conformation and a closed "engaged"
          conformation that aligns the PFD-TRiC substrate binding chambers. PFD can act after
          TRiC bound its substrates to enhance the rate and yield of the folding reaction
- term:
    id: GO:0001540
    label: amyloid-beta binding
  evidence_type: IDA
  original_reference_id: PMID:23614719
  review:
    summary: >-
      IDA annotation from Sorgjerd et al. 2013 (Biochemistry). The study demonstrated that
      recombinant human prefoldin (hPFD, the full heterohexameric complex) inhibits amyloid-beta
      (1-42) fibrillation and induces formation of soluble Abeta oligomers that are less toxic
      (30-40% less toxic than fibrils or archaeal PFD-formed oligomers). This demonstrates
      that the prefoldin complex as a whole binds amyloid-beta. However, the annotation is made
      at the level of individual subunits (PFDN6), whereas the binding is a property of the
      assembled hexamer complex, not of PFDN6 alone.
    action: KEEP_AS_NON_CORE
    reason: >-
      The amyloid-beta binding was demonstrated for the assembled prefoldin heterohexamer, not
      for PFDN6 individually. While technically each subunit participates in the complex that
      binds Abeta, this is not a core function of the gene product and may represent an in vitro
      property of the holo-complex rather than a physiological role of the individual subunit.
    supported_by:
      - reference_id: PMID:23614719
        supporting_text: >-
          we investigated the effect of recombinant human PFD (hPFD) on Aβ(1-42) aggregation
          in vitro and found that hPFD inhibited Aβ fibrillation and induced formation of
          soluble Aβ oligomers.
- term:
    id: GO:0016272
    label: prefoldin complex
  evidence_type: IDA
  original_reference_id: PMID:23614719
  review:
    summary: >-
      IDA annotation from Sorgjerd et al. 2013. The study used recombinant human prefoldin
      (assembled as a heterohexamer) demonstrating that PFDN6 is part of the complex.
    action: ACCEPT
    reason: >-
      Consistent with all other evidence for PFDN6 membership in the prefoldin complex.
    supported_by:
      - reference_id: PMID:23614719
        supporting_text: >-
          Prefoldin (PFD) is a molecular chaperone that prevents aggregation of misfolded proteins.
- term:
    id: GO:1905907
    label: negative regulation of amyloid fibril formation
  evidence_type: IDA
  original_reference_id: PMID:23614719
  review:
    summary: >-
      IDA annotation from Sorgjerd et al. 2013. The study showed that the full recombinant
      human prefoldin complex inhibits amyloid-beta fibrillation in vitro, with Abeta oligomers
      formed in the presence of hPFD being 30-40% less toxic. This is a property of the assembled
      prefoldin complex, not specific to PFDN6 individually. While interesting, this represents
      an in vitro observation with the holo-complex rather than a core physiological function
      of the PFDN6 gene product.
    action: KEEP_AS_NON_CORE
    reason: >-
      The negative regulation of amyloid fibril formation was demonstrated for the full prefoldin
      heterohexameric complex in vitro. While potentially relevant to Alzheimer's disease biology,
      this is not a core evolved function of PFDN6 specifically. The annotation is kept as non-core
      because the evidence is valid but represents a property of the holo-complex.
    supported_by:
      - reference_id: PMID:23614719
        supporting_text: >-
          hPFD inhibited Aβ fibrillation and induced formation of soluble Aβ oligomers.
          Interestingly, cell viability measurements ... showed that Aβ oligomers formed by
          hPFD were 30-40% less toxic
- term:
    id: GO:0016272
    label: prefoldin complex
  evidence_type: IDA
  original_reference_id: PMID:9630229
  review:
    summary: >-
      IDA annotation from the seminal Vainberg et al. 1998 (Cell) paper that first described
      the discovery of prefoldin as a heterohexameric chaperone. PFDN6 was identified as one
      of the six subunits of this complex.
    action: ACCEPT
    reason: >-
      Foundational experimental evidence from the original discovery of prefoldin.
    supported_by:
      - reference_id: PMID:9630229
        supporting_text: >-
          We describe the discovery of a heterohexameric chaperone protein, prefoldin,
          based on its ability to capture unfolded actin.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: NAS
  original_reference_id: PMID:9630229
  review:
    summary: >-
      NAS annotation from the original Vainberg et al. 1998 paper. The paper demonstrated
      that prefoldin captures unfolded actin and delivers it to the chaperonin. However, the
      molecular function is better described as GO:0044183 "protein folding chaperone" since
      prefoldin actively assists in folding rather than merely binding unfolded proteins.
    action: MODIFY
    reason: >-
      The original paper demonstrates that prefoldin's function goes beyond simple unfolded
      protein binding; it actively captures and transfers substrates to the chaperonin for
      productive folding. GO:0044183 "protein folding chaperone" is the more appropriate
      molecular function term.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
    supported_by:
      - reference_id: PMID:9630229
        supporting_text: >-
          Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target
          proteins to it ... prefoldin promotes folding in an environment in which there are
          many competing pathways for nonnative proteins.
- term:
    id: GO:0051087
    label: protein-folding chaperone binding
  evidence_type: IDA
  original_reference_id: PMID:9630229
  review:
    summary: >-
      IDA annotation from Vainberg et al. 1998. The paper directly demonstrated that prefoldin
      binds specifically to cytosolic chaperonin (c-CPN/TRiC/CCT) and transfers target proteins
      to it. This is strong direct experimental evidence for chaperonin binding.
    action: ACCEPT
    reason: >-
      Direct experimental demonstration that prefoldin binds specifically to the cytosolic
      chaperonin, which is the defining molecular interaction for prefoldin's function.
    supported_by:
      - reference_id: PMID:9630229
        supporting_text: >-
          Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target
          proteins to it.
- term:
    id: GO:0051131
    label: chaperone-mediated protein complex assembly
  evidence_type: IDA
  original_reference_id: PMID:9630229
  review:
    summary: >-
      IDA annotation from Vainberg et al. 1998. The paper showed that deletion of a prefoldin
      subunit gene in yeast results in impaired functions of the actin and tubulin-based
      cytoskeleton, demonstrating prefoldin's role in chaperone-mediated assembly of cytoskeletal
      complexes.
    action: ACCEPT
    reason: >-
      Direct experimental evidence from genetic studies showing that prefoldin is required for
      proper assembly of cytoskeletal protein complexes.
    supported_by:
      - reference_id: PMID:9630229
        supporting_text: >-
          Deletion of the gene encoding a prefoldin subunit in S. cerevisiae results in a
          phenotype similar to those found when c-cpn is mutated, namely impaired functions
          of the actin and tubulin-based cytoskeleton.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: NAS
  original_reference_id: PMID:9630229
  review:
    summary: >-
      NAS annotation from the original Vainberg et al. 1998 paper describing prefoldin's
      role in protein folding. The paper demonstrated that prefoldin promotes folding by
      directing target proteins to the chaperonin. Redundant with IDA and IBA annotations
      but consistent.
    action: ACCEPT
    reason: >-
      Consistent with the well-established protein folding function of prefoldin, supported
      by the foundational paper.
    supported_by:
      - reference_id: PMID:9630229
        supporting_text: >-
          we show that by directing target proteins to chaperonin, prefoldin promotes folding
          in an environment in which there are many competing pathways for nonnative proteins.
# New annotation suggestions
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: IDA
  original_reference_id: PMID:30955883
  review:
    summary: >-
      PFDN6, as a subunit of the prefoldin complex, functions as a protein folding chaperone
      that captures non-native substrates and delivers them to TRiC/CCT. This molecular function
      term is more appropriate than GO:0051082 "unfolded protein binding" because it captures the
      active co-chaperone role rather than passive binding. Gestaut et al. 2019 demonstrated that
      prefoldin alternates between conformations to align substrate binding chambers with TRiC/CCT
      and enhances the rate and yield of the folding reaction (PMID:30955883).
    action: NEW
    reason: >-
      GO:0044183 "protein folding chaperone" is the most appropriate molecular function term for
      prefoldin subunits. It is defined as "Binding to a protein or a protein-containing complex
      to assist the protein folding process" which exactly matches prefoldin's function. This
      annotation should replace the existing GO:0051082 annotations.
    supported_by:
      - reference_id: PMID:30955883
        supporting_text: >-
          PFD alternates between an open "latched" conformation and a closed "engaged"
          conformation that aligns the PFD-TRiC substrate binding chambers. PFD can act after
          TRiC bound its substrates to enhance the rate and yield of the folding reaction,
          suppressing non-productive reaction cycles.
      - reference_id: PMID:9630229
        supporting_text: >-
          Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target
          proteins to it ... prefoldin promotes folding in an environment in which there are
          many competing pathways for nonnative proteins.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:23614719
  title: 'Human prefoldin inhibits amyloid-β (Aβ) fibrillation and contributes to
    formation of nontoxic Aβ aggregates.'
  findings: []
- id: PMID:29662061
  title: RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone
    complex.
  findings: []
- id: PMID:30955883
  title: The Chaperonin TRiC/CCT Associates with Prefoldin through a Conserved Electrostatic
    Interface Essential for Cellular Proteostasis.
  findings: []
- id: PMID:31738558
  title: Upstream ORF-Encoded ASDURF Is a Novel Prefoldin-like Subunit of the PAQosome.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32699605
  title: The functions and mechanisms of prefoldin complex and prefoldin-subunits.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:34761191
  title: A comprehensive analysis of prefoldins and their implication in cancer.
  findings: []
- id: PMID:9630229
  title: Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin.
  findings: []
core_functions:
  - description: >-
      PFDN6 is a beta-type subunit of the heterohexameric prefoldin co-chaperone
      complex that captures unfolded nascent polypeptides (primarily actin and tubulin)
      and delivers them to the TRiC/CCT chaperonin for ATP-dependent folding.
      PFDN6 contributes a coiled-coil tentacle with hydrophobic residues that
      engages exposed hydrophobic patches on non-native substrates. Deletion of
      prefoldin subunit genes impairs actin and tubulin cytoskeleton function.
    molecular_function:
      id: GO:0044183
      label: protein folding chaperone
    directly_involved_in:
      - id: GO:0006457
        label: protein folding
      - id: GO:0051131
        label: chaperone-mediated protein complex assembly
    locations:
      - id: GO:0005737
        label: cytoplasm
    in_complex:
      id: GO:0016272
      label: prefoldin complex
    supported_by:
      - reference_id: PMID:9630229
        supporting_text: >-
          We describe the discovery of a heterohexameric chaperone protein, prefoldin,
          based on its ability to capture unfolded actin. Prefoldin binds specifically
          to cytosolic chaperonin (c-cpn) and transfers target proteins to it.
      - reference_id: PMID:30955883
        supporting_text: >-
          PFD can act after TRiC bound its substrates to enhance the rate and yield
          of the folding reaction, suppressing non-productive reaction cycles.

PFDN6

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Citations

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