HSP104 encodes the cytosolic Candida albicans Hsp100/ClpB-family AAA+ chaperone that resolves heat-damaged protein aggregates and supports induced thermotolerance. The protein is stress inducible, can functionally substitute for Saccharomyces cerevisiae Hsp104 in aggregate reactivation and prion propagation assays, and is required in C. albicans for efficient survival of lethal heat stress. Loss of HSP104 also compromises in vitro biofilm maturation and attenuates virulence in a room-temperature Caenorhabditis elegans infection model, consistent with a Candida-specific deployment of the conserved disaggregase during host-associated stress.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: HSP104 is a two-NBD AAA+ ATPase in the Hsp100/ClpB family, so ATP binding is a core sequence-supported molecular function. Reason: The InterPro transfer is appropriate. CaHsp104 has the conserved Hsp104 sequence features required for the ATP-driven disaggregase family and functionally complements an S. cerevisiae hsp104 mutant for heat-denatured protein reactivation. Supporting Evidence: PMID:16467463 CaHsp104 is able to provide all known functions of ScHsp104 in an S. cerevisiae hsp104 null mutant, i.e., tolerance to high-temperature stress, reactivation of heat-denatured proteins, and propagation of the [PSI+] prion. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: The broad-family PAINT assertion to cytoplasm is consistent with this Hsp104-like cytosolic paralog. Reason: CaHsp104 belongs to the cytosolic Hsp104 branch rather than the mitochondrial Hsp78 branch. The PAINT node behind this row is broad, but cytoplasm is shared by experimentally characterized fungal and bacterial descendants and is not contradicted by the Candida sequence or literature. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000181243 · PANTHER:PTN000181243 SUPPORTS TRANSFER Cytoplasm is placed at a broad PTHR11638 node; HSP104 is inside the fungal cytosolic disaggregase subtree descending from that placement. Supporting Evidence: PMID:16467463 the fungal pathogen Candida albicans carries an 899-residue stress-inducible orthologue of Hsp104 (CaHsp104) |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping agrees with the PAINT cytoplasm annotation for the cytosolic Hsp104 paralog. Reason: This electronic row is redundant with the IBA localization but is biologically correct for C. albicans Hsp104. Supporting Evidence: PMID:16467463 the fungal pathogen Candida albicans carries an 899-residue stress-inducible orthologue of Hsp104 (CaHsp104) |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: The fungal Hsp104 PAINT node correctly specializes the broad cytoplasm call to the cytosol. Reason: HSP104 is a fungal cytosolic Hsp104 ortholog, and the PTN007521008 row separates this clade from the fungal mitochondrial Hsp78 node. Transfer of cytosol to C. albicans HSP104 is therefore appropriate. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007521008 · PANTHER:PTN007521008 SUPPORTS TRANSFER The PAINT node is the fungal Hsp104 node, seeded by S. cerevisiae HSP104; C. albicans HSP104 sits in that same cytosolic orthologous clade. Supporting Evidence: PMID:16467463 CaHsp104 is able to provide all known functions of ScHsp104 in an S. cerevisiae hsp104 null mutant, i.e., tolerance to high-temperature stress, reactivation of heat-denatured proteins, and propagation of the [PSI+] prion. |
| GO:0006457 protein folding | IEA GO_REF:0000117 | MODIFY | Summary: The ARBA assertion captures the Hsp104 chaperone pathway, but the more precise process is protein refolding rather than de novo protein folding. Reason: Hsp104-family disaggregases act after proteins have misfolded and aggregated; they solubilize aggregates so Hsp70/Hsp40 can refold the liberated clients. The C. albicans protein reactivates heat-denatured proteins in an S. cerevisiae hsp104 mutant, so GO:0042026 is the better process term. Proposed replacements: protein refolding Supporting Evidence: PMID:16467463 CaHsp104 is able to provide all known functions of ScHsp104 in an S. cerevisiae hsp104 null mutant, i.e., tolerance to high-temperature stress, reactivation of heat-denatured proteins, and propagation of the [PSI+] prion. |
| GO:0009986 cell surface | IDA PMID:12543933 Sequential fractionation and two-dimensional gel analysis un... | UNDECIDED | Summary: HSP104 was annotated by CGD from a C. albicans cell-wall proteomics paper, but only the abstract is cached and it does not expose the HSP104 peptide assignment. Reason: Molecular chaperones can appear among fungal cell-surface moonlighting proteins, but HSP104's primary function is cytosolic disaggregation. The cached PMID:12543933 abstract reports mass-spectrometric identification of proteins classically associated with the cell wall and other compartments but does not show whether HSP104 was confidently assigned or surface exposed. Defer to CGD's full-text curation pending a direct check of the complete paper. Supporting Evidence: PMID:12543933 Mass spectrometry analyses have allowed the identification of several cell surface proteins classically associated with both the cell wall and other compartments. |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATP hydrolysis is the conserved biochemical activity that powers Hsp100/ClpB disaggregation. Reason: The broad-family PAINT assertion is appropriate for this AAA+ ATPase. CaHsp104 carries the conserved Hsp104 domains and complements the loss of S. cerevisiae Hsp104 for heat-stress tolerance and heat-denatured protein reactivation, which are ATP-dependent Hsp104 activities. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000181243 · PANTHER:PTN000181243 SUPPORTS TRANSFER ATP hydrolysis was placed at a broad ClpB-family node that contains HSP104; there is no Candida-specific loss of the AAA+ ATPase machinery. Supporting Evidence: PMID:16467463 CaHsp104 is able to provide all known functions of ScHsp104 in an S. cerevisiae hsp104 null mutant, i.e., tolerance to high-temperature stress, reactivation of heat-denatured proteins, and propagation of the [PSI+] prion. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: The InterPro AAA+ ATPase mapping to ATP hydrolysis agrees with the PAINT inference. Reason: HSP104 is an AAA+ Hsp100/ClpB ATPase whose conserved nucleotide-binding domains power its disaggregase activity. Supporting Evidence: PMID:16467463 The molecular chaperone Hsp104 is not only a key component of the cellular machinery induced to disassemble aggregated proteins in stressed cells of Saccharomyces cerevisiae but also plays an essential role in the propagation of the [PSI+], [URE3], and [RNQ/PIN+] prions in this organism. |
| GO:0034605 cellular response to heat | IEA GO_REF:0000117 | ACCEPT | Summary: Heat response is a well-supported C. albicans HSP104 process. Reason: The ARBA heat-response transfer is correct. C. albicans HSP104 is induced by elevated temperature, and hsp104 mutants are hypersensitive to lethal heat stress. Supporting Evidence: PMID:22635920 Mutants lacking HSP104 became hypersusceptible to lethally high temperatures, similarly to the corresponding mutants of Saccharomyces cerevisiae, whereas normal susceptibility was restored upon reintroduction of the gene. |
| GO:0034605 cellular response to heat | IMP PMID:21209325 Identification of sumoylation targets, combined with inactiv... | ACCEPT | Summary: Sumoylation-site mutants implicate Hsp104 regulation in C. albicans heat resistance. Reason: The paper identified Hsp104 as a C. albicans sumoylation target and showed that mutating its consensus SUMO site altered thermal-stress resistance, supporting a role for HSP104 in the cellular heat response. Supporting Evidence: PMID:21209325 Mutation of consensus sumoylation sites in Hsp60 and Hsp104 affected the resistance of C. albicans to thermal stress. |
| GO:0042026 protein refolding | IBA GO_REF:0000033 | ACCEPT | Summary: The fungal-node IBA correctly captures the refolding arm of Hsp104 disaggregase function. Reason: Hsp104 executes the protein-refolding pathway by extracting aggregated substrates that are then refolded by Hsp70/Hsp40. The C. albicans protein can substitute for S. cerevisiae Hsp104 in reactivation of heat-denatured proteins. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007521008 · PANTHER:PTN007521008 SUPPORTS TRANSFER Protein refolding was placed at the fungal Hsp104 node, and C. albicans HSP104 sits inside that subtree. Supporting Evidence: PMID:16467463 CaHsp104 is able to provide all known functions of ScHsp104 in an S. cerevisiae hsp104 null mutant, i.e., tolerance to high-temperature stress, reactivation of heat-denatured proteins, and propagation of the [PSI+] prion. |
| GO:0043335 protein unfolding | IBA GO_REF:0000033 | ACCEPT | Summary: Protein unfolding is the conserved mechanical step carried out by Hsp104/ClpB disaggregases. Reason: The fungal PAINT row is appropriate. Hsp104-family disaggregases extract and thread aggregated clients through the AAA+ pore, requiring unfolding, and CaHsp104 retains the functional Hsp104 activity that reactivates heat-denatured proteins in yeast. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007521008 · PANTHER:PTN007521008 SUPPORTS TRANSFER Protein unfolding is placed at the fungal Hsp104 node and supported by S. cerevisiae and S. pombe descendants; C. albicans HSP104 is not outside or divergent from that clade. Supporting Evidence: PMID:16467463 CaHsp104 is able to provide all known functions of ScHsp104 in an S. cerevisiae hsp104 null mutant, i.e., tolerance to high-temperature stress, reactivation of heat-denatured proteins, and propagation of the [PSI+] prion. |
| GO:0043335 protein unfolding | IEA GO_REF:0000117 | ACCEPT | Summary: The ARBA protein-unfolding annotation agrees with the fungal-node IBA and the Hsp104 disaggregase mechanism. Reason: CaHsp104 is a bona fide Hsp104-family disaggregase ortholog; protein unfolding is an integral part of the substrate-threading mechanism used by this family. Supporting Evidence: PMID:28375147 Hsp104 is a yeast member of the Hsp100 family which functions as a molecular chaperone to disaggregate misfolded polypeptides. |
| GO:0044011 single-species biofilm formation on inanimate substrate | IMP PMID:22635920 The heat-induced molecular disaggregase Hsp104 of Candida al... | KEEP AS NON CORE | Summary: C. albicans hsp104 mutants have a reproducible in vitro biofilm maturation defect. Reason: HSP104 loss impaired mature biofilm formation on two abiotic surfaces without measurably impairing initial adhesion, so this is an experimentally supported Candida-specific process. It should be kept as non-core because the likely molecular contribution is indirect proteostasis during stress rather than a dedicated adhesin or matrix-building activity. Supporting Evidence: PMID:22635920 biofilm formation by cells lacking HSP104 proved to be defective in two established in vitro models that use polystyrene and polyurethane as the substrates. |
| GO:0051087 protein-folding chaperone binding | IBA GO_REF:0000033 | ACCEPT | Summary: Hsp104 disaggregases function with the Hsp70/Hsp40 chaperone system, and the fungal-node PAINT transfer is appropriate. Reason: This molecular function is inherited from the fungal Hsp104 ancestor and matches the conserved multichaperone pathway used for aggregate reactivation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007521008 · PANTHER:PTN007521008 SUPPORTS TRANSFER The protein-folding chaperone binding assertion was placed at the fungal Hsp104 node from S. cerevisiae support; no Candida-specific evidence indicates loss of Hsp70/Hsp40 collaboration. Supporting Evidence: PMID:22635920 Hsp104 appears to be capable of resolving protein aggregates, allowing protein refolding ( 15 ), in cooperation with Hsp70, Hsp40, and trehalose ( 34 ). |
| GO:0070370 cellular heat acclimation | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT heat-acclimation call is correct for C. albicans HSP104 and is directly grounded by the target itself. Reason: The PTN007521008 node is seeded by Candida, S. pombe, and S. cerevisiae Hsp104 heat-tolerance evidence. C. albicans HSP104 being present in the IBA source list is expected because its mutant phenotype was used to place a conserved fungal Hsp104 assertion, not evidence of circularity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007521008 · PANTHER:PTN007521008 SUPPORTS TRANSFER Cellular heat acclimation is placed at the fungal Hsp104 node using C. albicans HSP104, S. pombe hsp104, and S. cerevisiae HSP104 as experimental descendants. Supporting Evidence: PMID:22635920 Mutants lacking HSP104 became hypersusceptible to lethally high temperatures, similarly to the corresponding mutants of Saccharomyces cerevisiae, whereas normal susceptibility was restored upon reintroduction of the gene. |
| GO:0070370 cellular heat acclimation | IMP PMID:22635920 The heat-induced molecular disaggregase Hsp104 of Candida al... | ACCEPT | Summary: Direct C. albicans mutant and reconstitution assays establish HSP104 as a thermotolerance factor. Reason: HSP104 deletion hypersensitized C. albicans to lethal heat stress, reintegration restored heat resistance, and ectopic HSP104 induction was sufficient to increase thermotolerance before heat shock. Supporting Evidence: PMID:22635920 Turning on expression of HSP104 prior to administration of the heat shock resulted in cells acquiring a greater thermotolerance with respect to cells of the wild-type strain |
| GO:0140545 ATP-dependent protein disaggregase activity | ISS PMID:16467463 The [PSI+] prion of Saccharomyces cerevisiae can be propagat... | NEW | Summary: HSP104 should gain the specific molecular-function term for ATP-dependent protein disaggregation. Reason: The existing GOA rows capture ATP hydrolysis and the protein-refolding and protein-unfolding processes, but not the integrated Hsp104 activity that uses ATP to resolubilize protein aggregates. CaHsp104 is a stress-induced Hsp104 ortholog that restores reactivation of heat-denatured proteins in an S. cerevisiae hsp104 null mutant. Supporting Evidence: PMID:16467463 CaHsp104 is able to provide all known functions of ScHsp104 in an S. cerevisiae hsp104 null mutant, i.e., tolerance to high-temperature stress, reactivation of heat-denatured proteins, and propagation of the [PSI+] prion. PMID:28375147 Hsp104 is a yeast member of the Hsp100 family which functions as a molecular chaperone to disaggregate misfolded polypeptides. |
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Download this section (compressed HTML)Q: Is the PMID:12543933 cell-surface assignment for HSP104 based on unique Hsp104 peptides and surface exposure, or should it be treated as a moonlighting-protein proteomics observation?
Q: Has native C. albicans Hsp104 disaggregase activity been reconstituted with purified C. albicans Hsp70/Hsp40 partners, or is the best direct molecular evidence still S. cerevisiae complementation?
Experiment: Purify C. albicans Hsp104 with cognate Hsp70 and Hsp40 partners and assay ATP-dependent resolubilization of heat-aggregated luciferase or an equivalent model substrate.
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