PFDN1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006457 protein folding	IBA GO_REF:0000033	ACCEPT	Summary: GO:0006457 "protein folding" is a well-supported core function of PFDN1. This IBA annotation was inferred from phylogenetic analysis (PANTHER) with evidence from yeast GimC/prefoldin (SGD:S000003715), Arabidopsis, and human PFDN1 itself. The prefoldin complex is a bona fide co-chaperone that captures unfolded nascent polypeptides (primarily actin and tubulin) and delivers them to TRiC/CCT for ATP-dependent folding (PMID:9630229). Gestaut et al. 2019 (PMID:30955883) showed that PFD enhances the rate and yield of TRiC-mediated folding, directly demonstrating involvement in protein folding. The Reactome pathway R-HSA-389957 "Prefoldin mediated transfer of substrate to CCT/TriC" also supports this annotation. This is the central biological process for PFDN1. Reason: Protein folding is the core biological process for all prefoldin subunits. The IBA annotation is phylogenetically well-supported and consistent with the extensive experimental literature demonstrating prefoldin's role in delivering substrates to TRiC/CCT for folding (PMID:9630229, PMID:30955883). 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. file:human/PFDN1/PFDN1-deep-research-falcon.md Prefoldin is a conserved hetero-hexameric cochaperone complex that binds non-native polypeptides, protects exposed hydrophobic regions to prevent aggregation, and transfers/shuttles folding clients to the cytosolic chaperonin TRiC/CCT for productive folding.
GO:0051082 unfolded protein binding	IBA GO_REF:0000033	MODIFY	Summary: GO:0051082 "unfolded protein binding" is now formally obsolete (go-ontology#30962). This IBA annotation was inferred from phylogenetic analysis (PANTHER) with evidence from yeast (SGD:S000003715) and human PFDN1 itself. While prefoldin does indeed bind unfolded proteins, the term "unfolded protein binding" is a pure binding term that fails to capture the functional significance of this interaction. Prefoldin acts as a holdase/transfer chaperone: it captures unfolded substrates (primarily actin and tubulin) and delivers them to the TRiC/CCT chaperonin for folding. As described in Vainberg et al. 1998 (PMID:9630229), "Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target proteins to it." The more appropriate term is GO:0044183 "protein folding chaperone" which captures the functional chaperone activity rather than just substrate binding. Notably, PFDN1 already has an IBA annotation to GO:0044183 in this same annotation set. Reason: GO:0051082 is now formally obsolete. The term describes only a binding activity and does not capture the chaperone function of prefoldin. Prefoldin is a molecular chaperone that binds unfolded substrates and delivers them to TRiC/CCT for folding (PMID:9630229, PMID:30955883). GO:0044183 "protein folding chaperone" (defined as "Binding to a protein or a protein-containing complex to assist the protein folding process") is the recommended replacement and already exists as a separate IBA annotation for this gene. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:9630229 Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target proteins to it. PMID:30955883 PFD alternates between an open "latched" conformation and a closed "engaged" conformation that aligns the PFD-TRiC substrate binding chambers.
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: GO:0005737 "cytoplasm" is an appropriate cellular component annotation for PFDN1. This IBA annotation was inferred from phylogenetic analysis (PANTHER) with evidence from C. elegans (WB:WBGene00007443). The prefoldin complex is a cytoplasmic chaperone that operates in the cytosol to capture unfolded nascent polypeptides and deliver them to the cytosolic chaperonin TRiC/CCT (PMID:9630229). The UniProt GO cross-references list this annotation, and the GOA qualifier "is_active_in" confirms that PFDN1 is active in the cytoplasm. Liang et al. 2020 (PMID:32699605) describe prefoldin as "a cytoplasmic chaperone protein." The term "cytoplasm" is appropriately broad, as a more specific CC annotation to "prefoldin complex" (GO:0016272) is already present in this annotation set. Having both is correct: one describes the subcellular location and the other describes the complex membership. Reason: PFDN1 operates as part of the cytoplasmic prefoldin complex. The cytoplasm annotation is well-supported and appropriately broad, complementing the more specific prefoldin complex (GO:0016272) annotation. The IBA phylogenetic inference is sound (PMID:9630229, PMID:32699605). Supporting Evidence: PMID:9630229 Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target proteins to it. PMID:32699605 As a cytoplasmic chaperone protein, the prefoldin complex is a hybrid oligomer assembled from six different proteins (six subunits).
GO:0044183 protein folding chaperone	IBA GO_REF:0000033	ACCEPT	Summary: GO:0044183 "protein folding chaperone" (defined as "Binding to a protein or a protein-containing complex to assist the protein folding process") is the most appropriate molecular function term for PFDN1. This IBA annotation was inferred from phylogenetic analysis (PANTHER) with evidence from human PFDN1 itself. Prefoldin functions as a holdase/transfer chaperone that captures unfolded nascent polypeptides and delivers them to TRiC/CCT for folding (PMID:9630229). Gestaut et al. 2019 (PMID:30955883) demonstrated that the PFD-TRiC supra-chaperone assembly enhances folding rates and suppresses non-productive reaction cycles. This term precisely captures the functional role of PFDN1 as a co-chaperone that assists in protein folding, and is also the recommended replacement for the obsoleting GO:0051082 "unfolded protein binding." Reason: This is the core molecular function of PFDN1. The prefoldin complex is a bona fide protein folding chaperone that captures unfolded substrates and delivers them to TRiC/CCT (PMID:9630229, PMID:30955883). The IBA annotation is phylogenetically well-supported and represents the best available MF term for prefoldin subunits. 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.
GO:0006457 protein folding	IEA GO_REF:0000002	ACCEPT	Summary: GO:0006457 "protein folding" inferred electronically from InterPro domain mapping (IPR002777, the prefoldin beta-like domain). This IEA annotation is consistent with the IBA and IDA annotations to the same term, and with the well-established role of the prefoldin complex in protein folding (PMID:9630229). The InterPro-to-GO mapping is appropriate for this domain. Reason: The IEA annotation to protein folding via InterPro is correct and consistent with the higher-confidence IBA and IDA annotations. The prefoldin beta-like domain (IPR002777) is specifically associated with the protein folding function of the prefoldin complex (PMID:9630229, PMID:30955883).
GO:0016272 prefoldin complex	IEA GO_REF:0000002	ACCEPT	Summary: GO:0016272 "prefoldin complex" inferred electronically from InterPro domain mapping (IPR002777, the prefoldin beta-like domain). PFDN1 is one of the four beta subunits (PFDN1, PFDN2, PFDN4, PFDN6) of the heterohexameric prefoldin complex (PMID:9630229, PMID:32699605). The complex is also registered in ComplexPortal as CPX-6149 and CPX-25767. This IEA annotation is consistent with the IDA annotations to the same term from PMID:30955883 and PMID:23614719. Reason: PFDN1 is a core structural subunit of the prefoldin complex. The IEA mapping from the prefoldin beta-like domain (IPR002777) to prefoldin complex membership is appropriate and consistent with experimental evidence (PMID:9630229, PMID:30955883).
GO:0032991 protein-containing complex	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: GO:0032991 "protein-containing complex" was inferred electronically by the ARBA machine learning model (ARBA:ARBA00028902). While technically correct -- PFDN1 is part of the prefoldin complex, which is indeed a protein-containing complex -- this annotation is redundant and overly general given the more specific GO:0016272 "prefoldin complex" annotation that is already present in this annotation set from both IEA (InterPro) and IDA (PMID:30955883, PMID:23614719) evidence. The term "protein-containing complex" adds no informational value beyond what is already captured. Reason: This is an overly general annotation. PFDN1 is part of the prefoldin complex (GO:0016272), which is a child term of protein-containing complex. The more specific term is already annotated with both IEA and IDA evidence. The generic "protein-containing complex" adds no useful information.
GO:0051082 unfolded protein binding	IEA GO_REF:0000002	MODIFY	Summary: GO:0051082 "unfolded protein binding" is now formally obsolete (go-ontology#30962). This IEA annotation was inferred electronically from InterPro domain mapping (IPR002777, the prefoldin beta-like domain). The InterPro-to-GO mapping associates the prefoldin domain with unfolded protein binding, which is functionally accurate in that prefoldin subunits do contact unfolded substrates. However, since the term is now formally obsolete, the annotation should be replaced with GO:0044183 "protein folding chaperone" which better describes the functional role of the prefoldin complex as a holdase/transfer chaperone that delivers substrates to TRiC/CCT. As noted by Liang et al. 2020 (PMID:32699605), "The prefoldin complex helps protein fold correctly and prevents aggregation by providing class II chaperones ... with a linear, unnatural substrate in the cytoplasm." Reason: GO:0051082 is now formally obsolete. While the InterPro mapping correctly identifies that the prefoldin domain binds unfolded proteins, the replacement term GO:0044183 "protein folding chaperone" better captures the functional role of prefoldin as a chaperone that assists in protein folding by delivering unfolded substrates to the TRiC/CCT chaperonin (PMID:32699605, PMID:9630229). Proposed replacements: protein folding chaperone Supporting Evidence: PMID:32699605 The prefoldin complex helps protein fold correctly and prevents aggregation by providing class II chaperones (Hsp60 molecular chaperones found in archaebacteria and eukaryotic cytoplasm) with a linear, unnatural substrate in the cytoplasm [2] PMID:9630229 Prefoldin binds specifically to cytosolic chaperonin (c-cpn) and transfers target proteins to it.
GO:0005515 protein binding	IPI PMID:16169070 A human protein-protein interaction network: a resource for ...	MARK AS OVER ANNOTATED	Summary: GO:0005515 "protein binding" (IPI with UniProtKB:Q9Y2X7/GIT1) from Stelzl et al. 2005 (PMID:16169070), a large-scale yeast two-hybrid screen of the human proteome. The interaction between PFDN1 and GIT1 (G protein-coupled receptor kinase interacting ArfGAP 1) was identified in this high-throughput screen. GIT1 is involved in cell signaling and cytoskeletal organization. While this could represent a biologically relevant interaction (GIT1 is involved in cytoskeletal remodeling, and prefoldin assists in actin/tubulin folding), the "protein binding" term is uninformative. However, the interaction itself is from a large-scale screen and may not reflect a direct functional relationship. Reason: "Protein binding" is an uninformative term that does not describe any specific molecular function. The interaction with GIT1 (Q9Y2X7) was detected in a high-throughput Y2H screen (PMID:16169070), and while the interaction may be real, the GO term provides no functional insight. More informative annotations such as GO:0044183 "protein folding chaperone" already capture the core binding function of PFDN1.
GO:0005515 protein binding	IPI PMID:16876117 Interaction of hepatitis C virus F protein with prefoldin 2 ...	MARK AS OVER ANNOTATED	Summary: GO:0005515 "protein binding" (IPI with UniProtKB:Q9UHV9/PFDN2) from Tsao et al. 2006 (PMID:16876117). This study used yeast two-hybrid and co-immunoprecipitation to demonstrate that HCV F protein interacts with PFDN2, and that HCV F protein "impeded the interaction between prefoldin 1 and 2." This confirms the PFDN1-PFDN2 interaction, which is expected since they are both subunits of the same heterohexameric prefoldin complex. The UniProt record confirms this interaction (NbExp=6). However, "protein binding" is uninformative -- this interaction reflects prefoldin complex assembly rather than a generic binding function. The annotation is not wrong but the term is too vague to be useful. Reason: "Protein binding" is uninformative. The PFDN1-PFDN2 interaction reflects subunit assembly within the prefoldin complex and is already captured by the GO:0016272 "prefoldin complex" CC annotation. The PMID:16876117 study was primarily about HCV F protein interaction with PFDN2, not PFDN1 function. Supporting Evidence: PMID:16876117 In the yeast three-hybrid system, it was found that expression of HCV F protein impeded the interaction between prefoldin 1 and 2.
GO:0005515 protein binding	IPI PMID:21900206 A directed protein interaction network for investigating int...	MARK AS OVER ANNOTATED	Summary: GO:0005515 "protein binding" (IPI with UniProtKB:Q9Y2X7/GIT1) from Vinayagam et al. 2011 (PMID:21900206), a directed protein interaction network study. This is a second independent detection of the PFDN1-GIT1 interaction (also seen in PMID:16169070). While the replication adds some confidence that the interaction is real, "protein binding" remains uninformative as a GO annotation for PFDN1. The biological significance of a PFDN1-GIT1 interaction is unclear. Reason: "Protein binding" is uninformative. This high-throughput interaction screen detection of PFDN1-GIT1 binding does not provide functional insight. The core molecular function of PFDN1 is already captured by GO:0044183 "protein folding chaperone."
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: GO:0005515 "protein binding" (IPI with UniProtKB:Q9UHV9/PFDN2) from Huttlin et al. 2017 (PMID:28514442), the BioPlex human interactome study. This is another independent detection of the PFDN1-PFDN2 intra-complex interaction, which is expected for subunits of the same hexameric complex. The "protein binding" term is uninformative and the interaction is already captured by the prefoldin complex membership annotation (GO:0016272). Reason: "Protein binding" is uninformative. The PFDN1-PFDN2 interaction reflects co-membership in the prefoldin complex, already captured by GO:0016272. This high-throughput interactome study provides no additional functional insight beyond complex membership.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: GO:0005515 "protein binding" (IPI with UniProtKB:Q9NPF5/DMAP1) from Luck et al. 2020 (PMID:32296183), a reference map of the human binary protein interactome (HuRI). DMAP1 (DNA methyltransferase 1-associated protein 1) is a component of NuA4/TIP60 histone acetyltransferase complex. The UniProt record for PFDN1 lists this interaction (NbExp=3). While the interaction may be real, its biological significance for PFDN1 function is unclear. DMAP1 is a nuclear protein whereas PFDN1 functions primarily in the cytoplasm. The "protein binding" term is uninformative. Reason: "Protein binding" is uninformative. The PFDN1-DMAP1 interaction was detected in a high-throughput binary interactome screen. The biological relevance is unclear given that PFDN1 is cytoplasmic and DMAP1 is nuclear. The core molecular function of PFDN1 is already captured by GO:0044183.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: GO:0005515 "protein binding" (IPI with UniProtKB:Q9UHV9/PFDN2 and UniProtKB:Q9Y2X7/GIT1) from Huttlin et al. 2021 (PMID:33961781), a dual proteome-scale network study of the human interactome. This confirms previously observed interactions: the PFDN1-PFDN2 interaction (intra-complex) and the PFDN1-GIT1 interaction. Both interactions have been detected in multiple independent studies. However, "protein binding" remains uninformative as a functional annotation. Reason: "Protein binding" is uninformative. These are replications of previously observed interactions (PFDN1-PFDN2 intra-complex; PFDN1-GIT1) that do not add functional insight beyond what is captured by GO:0016272 (prefoldin complex) and GO:0044183 (protein folding chaperone).
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: GO:0005515 "protein binding" (IPI with UniProtKB:Q9UHV9/PFDN2 and UniProtKB:Q9Y2X7/GIT1) from multimodal cell maps study (PMID:40205054). This is yet another replication of the PFDN1-PFDN2 and PFDN1-GIT1 interactions. The PFDN1-PFDN2 interaction is expected as both are subunits of the prefoldin complex. The "protein binding" term remains uninformative. Reason: "Protein binding" is uninformative. This is a further replication of known interactions (PFDN1-PFDN2, PFDN1-GIT1) from a large-scale study. The relevant functions are already captured by more specific annotations (GO:0044183, GO:0016272).
GO:0006457 protein folding	NAS PMID:32699605 The functions and mechanisms of prefoldin complex and prefol...	ACCEPT	Summary: GO:0006457 "protein folding" (NAS) from ComplexPortal, citing Liang et al. 2020 (PMID:32699605), a comprehensive review of prefoldin complex functions. The review describes how "the prefoldin complex helps protein fold correctly and prevents aggregation by providing class II chaperones ... with a linear, unnatural substrate in the cytoplasm." This NAS annotation is consistent with the IBA and IDA annotations to the same term and is well-supported by the review literature. Reason: Protein folding is the core biological process for PFDN1. This NAS annotation from ComplexPortal cites a well-sourced review (PMID:32699605) that accurately describes the protein folding function of the prefoldin complex. Consistent with IBA and IDA evidence to the same term. Supporting Evidence: PMID:32699605 The prefoldin complex helps protein fold correctly and prevents aggregation by providing class II chaperones (Hsp60 molecular chaperones found in archaebacteria and eukaryotic cytoplasm) with a linear, unnatural substrate in the cytoplasm [2]
GO:0006457 protein folding	NAS PMID:34761191 A comprehensive analysis of prefoldins and their implication...	ACCEPT	Summary: GO:0006457 "protein folding" (NAS) from ComplexPortal, citing Herranz-Montoya et al. 2021 (PMID:34761191), a comprehensive analysis of prefoldins and their implication in cancer. The review describes prefoldins as "evolutionary conserved co-chaperones" that "act as co-chaperones escorting misfolded or non-native proteins to group II chaperonins." This NAS annotation is consistent with the IBA and IDA annotations to the same term and is well-supported. Reason: Protein folding is the core biological process for PFDN1. This NAS annotation from ComplexPortal cites a comprehensive review (PMID:34761191) that accurately describes the co-chaperone function of prefoldin subunits. Consistent with IBA and IDA evidence. Supporting Evidence: PMID:34761191 PFDNs are prevalently organized into hetero-hexameric complexes. Although they have been overlooked since their discovery and their functions remain elusive, 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...	KEEP AS NON CORE	Summary: GO:0050821 "protein stabilization" (NAS) from ComplexPortal, citing Herranz-Montoya et al. 2021 (PMID:34761191). The GO definition of protein stabilization is "Any process involved in maintaining the structure and integrity of a protein and preventing it from degradation or aggregation." Prefoldin does prevent aggregation of unfolded substrates by capturing them and delivering them to TRiC/CCT (PMID:9630229). However, "protein stabilization" typically implies maintaining a folded protein in its native state, whereas prefoldin acts on unfolded nascent polypeptides as a holdase and transfer chaperone. The term is not entirely wrong -- prefoldin does prevent aggregation -- but it mischaracterizes the nature of the chaperone activity. The more accurate process annotation is GO:0006457 "protein folding," which is already well-annotated. Reason: While prefoldin does prevent protein aggregation (which is part of the GO definition of protein stabilization), the primary function is not to stabilize already-folded proteins but rather to capture unfolded substrates and transfer them to TRiC/CCT for folding. The annotation is not wrong but represents a secondary aspect of prefoldin function rather than its core activity. The core process (protein folding, GO:0006457) is already well-annotated with IBA, IDA, and NAS evidence. Supporting Evidence: PMID:34761191 PFDNs are prevalently organized into hetero-hexameric complexes. Although they have been overlooked since their discovery and their functions remain elusive, several reports indicate they act as co-chaperones escorting misfolded or non-native proteins to group II chaperonins.
GO:0006457 protein folding	IDA PMID:30955883 The Chaperonin TRiC/CCT Associates with Prefoldin through a ...	ACCEPT	Summary: GO:0006457 "protein folding" (IDA) from Gestaut et al. 2019 (PMID:30955883), which used cryo-EM, crosslinking mass spectrometry, and biochemical reconstitution to characterize the structural and functional interplay between the prefoldin (PFD) complex and TRiC/CCT chaperonin. The study demonstrates that "PFD can act after TRiC bound its substrates to enhance the rate and yield of the folding reaction, suppressing non-productive reaction cycles," directly showing involvement in protein folding. This is the highest-quality direct experimental evidence for the protein folding function of the prefoldin complex. Reason: This IDA annotation is supported by strong direct experimental evidence from Gestaut et al. 2019 (PMID:30955883), which demonstrated through cryo-EM and biochemical approaches that the PFD-TRiC supra-chaperone assembly enhances protein folding rates. Protein folding is the core biological process for PFDN1. 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. 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	IDA PMID:30955883 The Chaperonin TRiC/CCT Associates with Prefoldin through a ...	ACCEPT	Summary: GO:0016272 "prefoldin complex" (IDA) from Gestaut et al. 2019 (PMID:30955883). This study used reconstituted human prefoldin complex (containing all six subunits including PFDN1) and characterized its structure and function through cryo-EM, crosslinking mass spectrometry, and biochemical assays. The study resolved the architecture of the PFD-TRiC supra-chaperone complex, directly demonstrating that PFDN1 is a component of the prefoldin complex. The cryo-EM structures (PDB: 6NR8, 6NR9, 6NRB, 6NRC, 6NRD) include PFDN1 as a structural component. Reason: PFDN1 is a core structural subunit of the prefoldin complex. This IDA annotation is supported by high-resolution cryo-EM structural data from Gestaut et al. 2019 (PMID:30955883) that directly demonstrates PFDN1 as a component of the human prefoldin complex. Supporting Evidence: PMID:30955883 Maintaining proteostasis in eukaryotic protein folding involves cooperation of distinct chaperone systems. To understand how the essential ring-shaped chaperonin TRiC/CCT cooperates with the chaperone prefoldin/GIMc (PFD), we integrate cryoelectron microscopy (cryo-EM), crosslinking-mass-spectrometry and biochemical and cellular approaches to elucidate the structural and functional interplay between TRiC/CCT and PFD.
GO:0051082 unfolded protein binding	IDA PMID:30955883 The Chaperonin TRiC/CCT Associates with Prefoldin through a ...	MODIFY	Summary: GO:0051082 "unfolded protein binding" is now formally obsolete (go-ontology#30962). This IDA annotation cites Gestaut et al. 2019 (PMID:30955883), which used cryo-EM, crosslinking mass spectrometry, and biochemical reconstitution to characterize the structural and functional interplay between the prefoldin (PFD) complex and TRiC/CCT chaperonin. The study demonstrates that prefoldin associates with TRiC through a conserved electrostatic interface and undergoes conformational cycling between "latched" (open) and "engaged" (closed) states during substrate transfer. Critically, the paper shows that PFD functions not merely as a passive binder of unfolded substrates but as an active co-chaperone that "can act after TRiC bound its substrates to enhance the rate and yield of the folding reaction, suppressing non-productive reaction cycles." This demonstrates prefoldin is a bona fide protein folding chaperone. GO:0044183 "protein folding chaperone" is the appropriate replacement, capturing the functional role of prefoldin in the chaperone-assisted folding pathway. Reason: GO:0051082 is now formally obsolete. Gestaut et al. 2019 (PMID:30955883) demonstrates that prefoldin functions as a co-chaperone/holdase that cooperates with TRiC/CCT in substrate folding, not merely as an unfolded protein binder. The study shows prefoldin enhances the rate and yield of TRiC-mediated folding and that disrupting the PFD-TRiC interaction leads to accumulation of amyloid aggregates in vivo. GO:0044183 "protein folding chaperone" accurately describes this co-chaperone activity. Note that while prefoldin itself functions primarily as a holdase (it does not fold proteins on its own but transfers them to TRiC), the GO:0044183 definition ("Binding to a protein or a protein-containing complex to assist the protein folding process") appropriately encompasses this transfer/holdase function. Proposed replacements: protein folding chaperone 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. PMID:30955883 Disrupting the TRiC-PFD interaction in vivo is strongly deleterious, leading to accumulation of amyloid aggregates. PMID:30955883 The supra-chaperone assembly formed by PFD and TRiC is essential to prevent toxic conformations and ensure effective cellular proteostasis. 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:0001540 amyloid-beta binding	IDA PMID:23614719 Human prefoldin inhibits amyloid-β (Aβ) fibrillation and con...	KEEP AS NON CORE	Summary: GO:0001540 "amyloid-beta binding" (IDA) from Sorgjerd et al. 2013 (PMID:23614719). This study demonstrated that recombinant human prefoldin (hPFD) inhibits amyloid-beta (Abeta 1-42) fibrillation in vitro and induces formation of soluble Abeta oligomers with reduced toxicity. The study used thioflavin T measurements and immunoblotting to show that hPFD directly interacts with Abeta peptides and modifies their aggregation pathway. While this demonstrates that the prefoldin complex can bind Abeta, this is not the core function of PFDN1 -- it reflects the general chaperone/holdase property of prefoldin applied to an amyloidogenic substrate. The annotation was made on the intact prefoldin complex, not PFDN1 individually. Reason: Amyloid-beta binding is a secondary, non-core function that reflects the general holdase/chaperone activity of the prefoldin complex applied to an amyloidogenic substrate. The study (PMID:23614719) used the intact hexameric complex rather than individual PFDN1. While the data are solid, this represents a peripheral function compared to the core role in actin/tubulin folding via TRiC/CCT delivery. Supporting Evidence: PMID:23614719 we investigated the effect of recombinant human PFD (hPFD) on Abeta(1-42) aggregation in vitro and found that hPFD inhibited Abeta fibrillation and induced formation of soluble Abeta oligomers.
GO:0016272 prefoldin complex	IDA PMID:23614719 Human prefoldin inhibits amyloid-β (Aβ) fibrillation and con...	ACCEPT	Summary: GO:0016272 "prefoldin complex" (IDA) from Sorgjerd et al. 2013 (PMID:23614719). This study expressed and purified recombinant human prefoldin complex (hPFD) to investigate its effect on amyloid-beta aggregation. The successful reconstitution and purification of the hexameric complex containing PFDN1 provides direct evidence for PFDN1 membership in the prefoldin complex. This is consistent with the IDA annotation from PMID:30955883 and the IEA annotation from InterPro. Reason: PFDN1 is a core structural subunit of the prefoldin complex. This IDA annotation from PMID:23614719 provides independent experimental evidence through reconstitution of the human prefoldin hexamer, consistent with the structural data from PMID:30955883. 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: GO:1905907 "negative regulation of amyloid fibril formation" (IDA) from Sorgjerd et al. 2013 (PMID:23614719). The study demonstrated that recombinant human prefoldin "inhibited Abeta fibrillation and induced formation of soluble Abeta oligomers" that were 30-40% less toxic than Abeta fibrils. Thioflavin T measurements confirmed reduced fibril formation. While the experimental evidence is sound, this represents a non-core function of the prefoldin complex -- an extension of its general holdase/chaperone properties to amyloidogenic substrates rather than its primary role in actin/tubulin folding. The study was performed on the intact hexameric complex, not PFDN1 individually. Reason: The experimental evidence from PMID:23614719 is solid, but this is a secondary function reflecting the general anti-aggregation properties of the prefoldin complex rather than its core role in delivering unfolded actin/tubulin to TRiC/CCT. The study was performed in vitro on the intact hexameric complex, and the relevance to PFDN1 specifically (as opposed to the complex as a whole) is indirect. Supporting Evidence: PMID:23614719 we investigated the effect of recombinant human PFD (hPFD) on Abeta(1-42) aggregation in vitro and found that hPFD inhibited Abeta fibrillation and induced formation of soluble Abeta oligomers. PMID:23614719 Our findings show a relation between cytotoxicity of Abeta oligomers and structure and suggest a possible protective role of PFD in AD.
GO:0044183 protein folding chaperone	IPI PMID:16876117 Interaction of hepatitis C virus F protein with prefoldin 2 ...	ACCEPT	Summary: GO:0044183 "protein folding chaperone" (IPI with UniProtKB:Q9UHV9/PFDN2) from Tsao et al. 2006 (PMID:16876117), annotated by AgBase. This study demonstrated that HCV F protein interacts with PFDN2 and that this interaction "impeded the interaction between prefoldin 1 and 2," resulting in "aberrant organization of tubulin cytoskeleton." The study describes prefoldin as "a hexameric molecular chaperone complex ... which delivers nascent actin and tubulin proteins to the eukaryotic cytosolic chaperonin for facilitated folding." The IPI evidence code is appropriate because the chaperone function of PFDN1 was demonstrated through its interaction with PFDN2 in the context of prefoldin complex assembly and function. The study shows that disrupting the PFDN1-PFDN2 interaction (via HCV F protein) impairs the chaperone function of the complex, providing indirect evidence that PFDN1 enables protein folding chaperone activity through the complex. Reason: GO:0044183 "protein folding chaperone" is the core molecular function of PFDN1. This IPI annotation is supported by PMID:16876117, which demonstrates that PFDN1-PFDN2 interaction is essential for prefoldin complex assembly and chaperone function. Disruption of this interaction by HCV F protein leads to aberrant tubulin cytoskeleton, confirming the functional significance. Supporting Evidence: PMID:16876117 Prefoldin 2 is a subunit of a hexameric molecular chaperone complex, named prefoldin, which delivers nascent actin and tubulin proteins to the eukaryotic cytosolic chaperonin for facilitated folding. PMID:16876117 In the yeast three-hybrid system, it was found that expression of HCV F protein impeded the interaction between prefoldin 1 and 2.

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

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