HSP78

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005515 protein binding	IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine...	REMOVE	Summary: This generic protein-binding row comes from a genome-scale AP-MS survey and does not state an informative HSP78 molecular function. Reason: Hsp78 has a well-defined ATP-dependent disaggregase activity and a mitochondrial client-binding role. A high-throughput physical interaction with the cytosolic Hsp70 Ssa1 is too generic to keep as a standalone molecular-function annotation for this mitochondrial matrix protein. Supporting Evidence: PMID:16429126 Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry.
GO:0005515 protein binding	IPI PMID:23217712 CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abund...	REMOVE	Summary: The Ssa1 interactome evidence is generic and should not stand as a core HSP78 molecular-function annotation. Reason: This paper focuses on CDK-dependent Ssa1 phosphorylation and client regulation. The HSP78 row reports generic protein binding to Ssa1 rather than the direct Hsp78 activity on misfolded mitochondrial clients, which is already captured by GO:0051787 and the proposed GO:0140545 row. Supporting Evidence: PMID:23217712 In budding yeast, the essential functions of Hsp70 chaperones Ssa1-4 are regulated through expression level, isoform specificity, and cochaperone activity.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: Hsp78 contains the conserved Hsp100/ClpB AAA+ ATP-binding domains. Reason: The sequence-based InterPro inference agrees with direct work showing that Hsp78 forms an ATP-dependent hexamer and hydrolyzes ATP. Supporting Evidence: PMID:11734006 Here, Hsp78 was purified to homogeneity and shown to form a homo-hexameric complex, with an apparent molecular mass of approximately 440 kDa, in an ATP-dependent manner.
GO:0005737 cytoplasm	IBA GO_REF:0000033	MODIFY	Summary: The cytoplasm IBA is a true but over-broad parent of Hsp78's matrix localization. Reason: HSP78 is active in the mitochondrial matrix, which is part of the mitochondrion and therefore part of the cytoplasm. The PTN000181243 cytoplasm assertion does transfer, but it is only a true parent; the fungal Hsp78 node PTN000909045 already provides the more informative mitochondrial matrix location. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000181243 · PANTHER:PTN000181243 SUPPORTS TRANSFER The node is broader than the fungal mitochondrial Hsp78 subtree and propagates a true but uninformative cytoplasm parent rather than the matrix compartment that directly describes Hsp78. Proposed replacements: mitochondrial matrix
GO:0005739 mitochondrion	HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen...	ACCEPT	Summary: High-throughput mitochondrial proteomics is consistent with Hsp78's direct mitochondrial-matrix localization. Reason: Hsp78 had already been directly localized to the mitochondrial matrix, so a mitochondrial proteome hit is a sound supporting location annotation. Supporting Evidence: PMID:8413229 Submitochondrial fractionation showed that hsp78 is a soluble protein located in the mitochondrial matrix.
GO:0005739 mitochondrion	HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph...	ACCEPT	Summary: The quantitative mitochondrial proteome assignment agrees with direct mitochondrial-matrix localization. Reason: This HDA row is broad, but it is not misleading because the direct 1993 fractionation paper and PAINT both place Hsp78 in the mitochondrial matrix. Supporting Evidence: PMID:8413229 Submitochondrial fractionation showed that hsp78 is a soluble protein located in the mitochondrial matrix.
GO:0005759 mitochondrial matrix	IBA GO_REF:0000033	ACCEPT	Summary: PTN000909045 is the fungal mitochondrial Hsp78 node and correctly places HSP78 in the mitochondrial matrix. Reason: The target appears among the experimental descendants that PAINT used to place this matrix assertion; that is expected and confirms the node is grounded in direct SGD HSP78 evidence, not a circular transfer. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000909045 · PANTHER:PTN000909045 SUPPORTS TRANSFER The fungal Hsp78 node is seeded by the target's own direct mitochondrial-matrix annotation, which supports ancestral placement. Supporting Evidence: PMID:8413229 Submitochondrial fractionation showed that hsp78 is a soluble protein located in the mitochondrial matrix.
GO:0005759 mitochondrial matrix	IDA PMID:8413229 HSP78 encodes a yeast mitochondrial heat shock protein in th...	ACCEPT	Summary: Direct submitochondrial fractionation established soluble mitochondrial-matrix localization for Hsp78. Reason: This is the direct source for Hsp78's correct compartment. Supporting Evidence: PMID:8413229 Submitochondrial fractionation showed that hsp78 is a soluble protein located in the mitochondrial matrix.
GO:0005759 mitochondrial matrix	IEA GO_REF:0000044	ACCEPT	Summary: The UniProt subcellular-location mapping agrees with direct mitochondrial-matrix evidence. Reason: The electronic location row is redundant with direct and PAINT matrix rows, but it is biologically correct for Hsp78.
GO:0006457 protein folding	IEA GO_REF:0000117	MODIFY	Summary: Hsp78 acts in resolubilization and refolding of damaged mitochondrial proteins, so generic protein folding should be refined. Reason: Hsp78 is not a general de novo folding chaperone. It cooperates with the mitochondrial Hsp70 system to reactivate substrates after heat-induced aggregation, making GO:0042026 protein refolding the better process term. Proposed replacements: protein refolding Supporting Evidence: PMID:11734006 Studies on the chaperone activity of Hsp78 show that its cooperation with the mitochondrial Hsp70 system, consisting of Ssc1p, Mdj1p and Mge1p, is needed for the efficient reactivation of substrate proteins.
GO:0016887 ATP hydrolysis activity	IBA GO_REF:0000033	ACCEPT	Summary: The broad PAINT node is appropriate for the conserved Hsp100/ClpB ATPase activity. Reason: ATP hydrolysis is shared by fungal cytosolic Hsp104 and mitochondrial Hsp78 proteins and was directly shown for purified Hsp78. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000181243 · PANTHER:PTN000181243 SUPPORTS TRANSFER The broad node is acceptable for ATP hydrolysis because both Hsp104 and Hsp78 retained the AAA+ catalytic subactivity. Supporting Evidence: PMID:11734006 Analysis of its ATPase activity reveals that the observed positive cooperativity effect depends both on Hsp78 and ATP concentration.
GO:0016887 ATP hydrolysis activity	IDA PMID:11734006 Importance of two ATP-binding sites for oligomerization, ATP...	ACCEPT	Summary: Purified Hsp78 has ATPase activity. Reason: Krzewska and colleagues directly assayed ATP hydrolysis by purified Hsp78 and showed that mutating the first nucleotide-binding domain affects this ATPase activity. Supporting Evidence: PMID:11734006 Analysis of its ATPase activity reveals that the observed positive cooperativity effect depends both on Hsp78 and ATP concentration.
GO:0016887 ATP hydrolysis activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated transfer of ATP hydrolysis agrees with direct Hsp78 ATPase assays. Reason: This IEA row is generic but correct for an experimentally verified Hsp100/ClpB AAA+ ATPase. Supporting Evidence: PMID:11734006 Analysis of its ATPase activity reveals that the observed positive cooperativity effect depends both on Hsp78 and ATP concentration.
GO:0016887 ATP hydrolysis activity	IMP PMID:11734006 Importance of two ATP-binding sites for oligomerization, ATP...	ACCEPT	Summary: Nucleotide-binding-domain mutagenesis confirmed the link between Hsp78 sequence features and ATPase activity. Reason: The mutant analysis in the purified-protein paper supports the same ATPase molecular function as the direct assay. Supporting Evidence: PMID:11734006 Site-directed mutagenesis of the two putative Hsp78 nucleotide-binding domains suggest that the first nucleotide-binding domain is responsible for ATP hydrolysis and the second one for protein oligomerization.
GO:0034605 cellular response to heat	IBA GO_REF:0000033	ACCEPT	Summary: The broad PAINT heat-response row is valid for mitochondrial Hsp78. Reason: Hsp78 protects mitochondria during severe temperature stress, so heat-response function is shared across the Hsp100/ClpB branches placed under this broader PAINT node. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000181243 · PANTHER:PTN000181243 SUPPORTS TRANSFER Heat response is not restricted to cytosolic Hsp104; mitochondrial Hsp78 also protects organelle function under heat stress. Supporting Evidence: PMID:8830768 Hsp78 is crucial for maintenance of respiratory competence and for mitochondrial genome integrity under severe temperature stress (mitochondrial thermotolerance).
GO:0034605 cellular response to heat	IEA GO_REF:0000117	ACCEPT	Summary: The ARBA heat-response assertion is broad but sound for Hsp78. Reason: HSP78 expression is heat regulated and Hsp78 protects mitochondrial function after heat stress. Supporting Evidence: PMID:8413229 The steady-state levels of HSP78 transcripts and protein varied in response to both thermal stress and carbon source
GO:0034605 cellular response to heat	IGI PMID:8830768 The molecular chaperone Hsp78 confers compartment-specific t...	ACCEPT	Summary: Cytosolic Hsp78 can substitute for Hsp104 in cellular thermotolerance, supporting a conserved heat-response activity. Reason: The IGI row is contextual because native Hsp78 is mitochondrial, but it demonstrates that the Hsp78 AAA+ disaggregase module can perform the same heat-protective activity as Hsp104 when placed in the cytosol. Supporting Evidence: PMID:8830768 When expressed in the cytosol, Hsp78 can substitute for the homologous heat shock protein Hsp104 in mediating cellular thermotolerance
GO:0034605 cellular response to heat	IMP PMID:7628444 Hsp78, a Clp homologue within mitochondria, can substitute f...	ACCEPT	Summary: Hsp78 supports mitochondrial protein homeostasis in a sensitized temperature-stress background. Reason: The mtHsp70 sensitized background exposes Hsp78's role as a stress chaperone for mitochondrial matrix proteins. Supporting Evidence: PMID:7628444 results in a petite phenotype in the ssc1-3 mutant strain carrying a temperature-sensitive allele of mt-hsp70
GO:0034605 cellular response to heat	IMP PMID:8830768 The molecular chaperone Hsp78 confers compartment-specific t...	ACCEPT	Summary: HSP78 is required for mitochondrial thermotolerance after severe heat stress. Reason: Hsp78 protects respiratory competence, mitochondrial genome integrity, and mitochondrial protein synthesis during recovery from severe heat stress. Supporting Evidence: PMID:8830768 Hsp78 is crucial for maintenance of respiratory competence and for mitochondrial genome integrity under severe temperature stress (mitochondrial thermotolerance).
GO:0042026 protein refolding	IBA GO_REF:0000033	ACCEPT	Summary: The protein-refolding IBA is placed on the correct fungal Hsp78 node. Reason: Protein refolding captures the outcome of Hsp78-mediated aggregate resolubilization with the mitochondrial Hsp70 system. The target's direct SGD annotation supports the PAINT placement at PTN000909045. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000909045 · PANTHER:PTN000909045 SUPPORTS TRANSFER HSP78 itself is an experimental descendant for the fungal Hsp78 node, which strengthens rather than weakens the IBA. Supporting Evidence: PMID:11734006 Studies on the chaperone activity of Hsp78 show that its cooperation with the mitochondrial Hsp70 system, consisting of Ssc1p, Mdj1p and Mge1p, is needed for the efficient reactivation of substrate proteins.
GO:0042026 protein refolding	IDA PMID:11734006 Importance of two ATP-binding sites for oligomerization, ATP...	ACCEPT	Summary: Direct Hsp78 chaperone assays support reactivation/refolding of substrate proteins with the mitochondrial Hsp70 system. Reason: Purified Hsp78 requires cooperation with Ssc1, Mdj1, and Mge1 to efficiently reactivate substrate proteins, matching protein refolding. Supporting Evidence: PMID:11734006 Studies on the chaperone activity of Hsp78 show that its cooperation with the mitochondrial Hsp70 system, consisting of Ssc1p, Mdj1p and Mge1p, is needed for the efficient reactivation of substrate proteins.
GO:0042026 protein refolding	IMP PMID:11734006 Importance of two ATP-binding sites for oligomerization, ATP...	ACCEPT	Summary: Mutagenesis of the two Hsp78 ATP-binding sites supports the ATP-dependent chaperone mechanism. Reason: Perturbing the nucleotide-binding domains separated ATP hydrolysis and oligomerization defects and confirmed that these modules are needed for Hsp78 chaperone activity. Supporting Evidence: PMID:11734006 These studies also suggest that the oligomerization but not the Hsp78 ATPase activity is essential for its chaperone activity.
GO:0043335 protein unfolding	IBA GO_REF:0000033	ACCEPT	Summary: The fungal Hsp78 PAINT node correctly asserts the ATP-driven unfolding step of protein disaggregation. Reason: Hsp78 is the mitochondrial ClpB homolog that performs ATP-dependent aggregate resolubilization; protein unfolding represents the extraction and threading step used to release aggregated clients. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000909045 · PANTHER:PTN000909045 SUPPORTS TRANSFER Protein unfolding is placed on the fungal Hsp78 subtree seeded by SGD HSP78. Supporting Evidence: PMID:16460754 Hsp78 is indispensable for the resolubilization of protein aggregates generated by heat stress under in vivo conditions.
GO:0043335 protein unfolding	IEA GO_REF:0000117	ACCEPT	Summary: The ARBA protein-unfolding row is consistent with Hsp78 disaggregation. Reason: ATP-dependent extraction/unfolding is the direct mechanism by which Hsp78 resolubilizes mitochondrial protein aggregates. Supporting Evidence: PMID:16460754 Hsp78 is indispensable for the resolubilization of protein aggregates generated by heat stress under in vivo conditions.
GO:0043335 protein unfolding	IMP PMID:16460754 The disaggregation activity of the mitochondrial ClpB homolo...	ACCEPT	Summary: In intact mitochondria, Hsp78 is required for ATP-dependent disaggregation of heat-generated aggregates. Reason: The in-organello disaggregation assay directly established the ATP-dependent activity that resolubilizes aggregated mitochondrial proteins. Supporting Evidence: PMID:16460754 By establishing an aggregation/disaggregation assay in intact mitochondria we demonstrated that Hsp78 is indispensable for the resolubilization of protein aggregates generated by heat stress under in vivo conditions.
GO:0050821 protein stabilization	IGI PMID:7628444 Hsp78, a Clp homologue within mitochondria, can substitute f...	ACCEPT	Summary: Hsp78 maintains matrix proteins in a soluble state when mtHsp70 function is compromised. Reason: The ssc1 genetic interaction showed that Hsp78 can act as a matrix salvage chaperone that prevents misfolded mitochondrial proteins from aggregating when the main mitochondrial Hsp70 system is impaired. Supporting Evidence: PMID:7628444 As a molecular chaperone, hsp78 prevents the aggregation of misfolded proteins in the matrix of mitochondria under conditions of impaired mt-hsp70 function.
GO:0050821 protein stabilization	IMP PMID:16460754 The disaggregation activity of the mitochondrial ClpB homolo...	ACCEPT	Summary: Hsp78 keeps aggregated Ssc1 recoverable and functional after heat stress. Reason: The 2006 study showed that ATP-dependent Hsp78 disaggregation restores a heat-destabilized Ssc1 mutant, supporting maintenance of mitochondrial Hsp70 in a soluble and functional state. Supporting Evidence: PMID:16460754 We conclude that the protective role of Hsp78 in thermotolerance is mainly based on maintaining the molecular chaperone Ssc1 in a soluble and functional state.
GO:0051787 misfolded protein binding	IDA PMID:7628444 Hsp78, a Clp homologue within mitochondria, can substitute f...	ACCEPT	Summary: Hsp78 directly binds newly imported, misfolded mitochondrial polypeptides. Reason: Misfolded protein binding is the relevant client-binding molecular function for Hsp78 and is more informative than generic protein binding. Supporting Evidence: PMID:7628444 hsp78 suppresses the defect in mitochondrial protein import under permissive conditions in vitro and interacts directly with newly imported polypeptide chains.
GO:0070013 intracellular organelle lumen	IEA GO_REF:0000117	MODIFY	Summary: The ARBA organelle-lumen row points in the right direction but should be specialized to mitochondrial matrix. Reason: Hsp78 is not just somewhere in an organelle lumen; it is a soluble mitochondrial matrix disaggregase, as shown by submitochondrial fractionation and by the Hsp78-specific PAINT node. Proposed replacements: mitochondrial matrix Supporting Evidence: PMID:8413229 Submitochondrial fractionation showed that hsp78 is a soluble protein located in the mitochondrial matrix.
GO:0140545 ATP-dependent protein disaggregase activity	IDA PMID:16460754 The disaggregation activity of the mitochondrial ClpB homolo...	NEW	Summary: HSP78 should gain the specific integrated molecular-function term for its ATP-dependent disaggregase activity. Reason: Existing annotations cover ATP hydrolysis plus protein refolding and unfolding processes, but GO:0140545 directly names the Hsp78 activity that couples ATP hydrolysis to extraction of polypeptides from aggregates. Supporting Evidence: PMID:16460754 The ATP-dependent disaggregation activity of Hsp78 was capable of reversing the preprotein import defect of a destabilized mutant form of Ssc1.

Gene Description

Existing Annotations Review

Core Functions

Mitochondrial Hsp100/ClpB activity that uses ATP hydrolysis to extract aggregated matrix polypeptides, resolubilize them, and return them to the Ssc1/Mdj1/Mge1 mitochondrial Hsp70 system for refolding after heat stress.

Direct binding to misfolded or newly imported mitochondrial polypeptides that underlies aggregate handling by the Hsp78 disaggregase.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

SGD

SGD gene description for HSP78 (yeast)

📚 Additional Documentation

Notes

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