Hsp82 is the stress-inducible cytosolic Hsp90 paralog in S. cerevisiae and shares about 97% amino-acid identity with the constitutively expressed Hsc82. It is a homodimeric ATP-dependent molecular chaperone that promotes late-stage folding, activation, and structural maintenance of selected client proteins, including the MAPKKK Ste11 and transcriptional regulators. ATP binding, nucleotide-state exchange, conformational transitions, and cochaperones such as Sti1, Aha1, Cdc37, and Sba1 together control client loading, maturation, and release. Hsp82 is expressed at low abundance under nonstress conditions, is strongly induced by heat, and is more thermally stable than Hsc82. It is predominantly cytosolic during vegetative growth and can accumulate in the nucleus during quiescence and sporulation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006457 protein folding | IBA GO_REF:0000033 | ACCEPT | Summary: HSP82/Hsp90 is a well-established protein folding chaperone. IBA annotation is consistent with the known function of this conserved chaperone family across eukaryotes. Falcon deep research frames Hsp82 as a selective proteostasis hub that assists late-stage folding, activation, and stability of specific client proteins rather than acting as a general chaperone for all misfolded proteins. Reason: Protein folding is a core biological process for Hsp90. UniProt describes HSP82 as a "Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins." Multiple IMP and IDA evidence codes confirm involvement in selective client-protein folding (PMID:10564510, PMID:9371781). Supporting Evidence: file:yeast/HSP82/HSP82-deep-research-falcon.md Hsp82 (Hsp90) is an **ATP-dependent molecular chaperone** that assists the **late-stage folding, activation, and stability** of a large set of specific file:yeast/HSP82/HSP82-deep-research-falcon.md Hsp90/Hsp82 is best understood as a **proteostasis hub** rather than a general chaperone for all misfolded proteins |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: HSP82 has well-characterized ATPase activity that regulates its conformational chaperone cycle. The IBA annotation is correct. Falcon deep research places ATP hydrolysis within the dimeric open/closed conformational cycle, noting that the constitutive paralog Hsc82 has somewhat higher ATPase activity than Hsp82 (~1.3-fold at 30C, ~1.6-fold at 37C), with kinetic differences mapping to N-terminal-domain substitutions near the nucleotide pocket. Reason: ATP hydrolysis and nucleotide exchange are conserved features of the Hsp90 cycle and ATPase activity is directly demonstrated for yeast Hsp90 (PMID:12235160). The activity annotation does not require the stronger claim that hydrolysis rate alone determines every essential in vivo function. Supporting Evidence: file:yeast/HSP82/HSP82-deep-research-falcon.md Client loading, conformational closing, ATP hydrolysis/nucleotide exchange, and reopening are **regulated by co-chaperones** that bind distinct surfaces and bias the timing of transitions file:yeast/HSP82/HSP82-deep-research-falcon.md Hsc82 exhibits **higher ATPase activity** than Hsp82 at both 30°C and 37°C in comparative assays, and kinetic differences map largely to N-terminal-domain substitutions near the nucleotide pocket |
| GO:0032991 protein-containing complex | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: HSP82 forms Hsp90 dimers and many co-chaperone/client assemblies, but the generic protein-containing complex term does not identify a biologically meaningful assembly. Reason: Hsp82 genuinely participates in homodimers and specific client/co-chaperone complexes, but GO:0032991 is too broad to convey any of those assemblies. The more informative annotation is ATP-dependent protein folding chaperone activity together with experimentally supported dimerization. The full-length Hsp82-ATP-analogue-Sba1 crystal structure preserves the concrete complex evidence even though no specific complex term is proposed here. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000163629 · PAINT Hsp90 family node SUPPORTS TRANSFER Hsp90 proteins genuinely form dimers and client/co-chaperone assemblies, but the propagated protein-containing complex term is too generic to identify any such assembly. Supporting Evidence: PMID:16625188 Here we present the crystal structure of full-length yeast Hsp90 in complex with an ATP analogue and the co-chaperone p23/Sba1. file:yeast/HSP82/HSP82-deep-research-falcon.md Yeast has ~14 Hsp90 co-chaperones (diverse domain architectures) that **target clients**, **modulate ATPase activity**, and **stabilize or destabilize** conformational states |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: The IBA transfers plasma-membrane localization from other Hsp90 descendants, whereas direct imaging identifies Hsp82 as a highly abundant cytosolic protein. Reason: HSP82 is an abundant soluble cytosolic chaperone. Targeted GFP imaging showed a prominent cytosolic distribution, and the retrieved literature provides no evidence for a stable functional plasma-membrane pool in budding yeast. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000163629 · PAINT Hsp90 family node SUPPORTS SOURCE BUT NOT TARGET Plasma-membrane localization may occur for some Hsp90 descendants, but direct imaging places this abundant soluble yeast isoform in the cytosol and does not establish membrane residence. Supporting Evidence: PMID:27385335 Each of these candidates (Cdc19, Gpp1, Hsp82, Pgk1, and Tpi1), when expressed as a C-terminally GFP-tagged derivative from its endogenous promoter at its native chromosomal locus, exhibited a very prominent cytosolic distribution |
| GO:0005524 ATP binding | IBA GO_REF:0000033 | ACCEPT | Summary: HSP82 binds ATP as part of its chaperone cycle. Well-established by crystallography. Reason: ATP binding is essential for Hsp90 function. Multiple crystal structures show ATP/ADP binding (PDB:1AM1, 1AMW, 2CG9). UniProt documents extensive ATP binding site residues. The functional cycle is linked to ATP binding and hydrolysis. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: HSP82 is a cytosolic protein. IBA annotation is correct. Falcon deep research confirms that cytosolic Hsp90 (Hsp82/Hsc82) is broadly distributed during vegetative growth. Reason: Consistent with IDA evidence for cytoplasm localization (PMID:32920053, PMID:27385335) and HDA data (PMID:11914276, PMID:14562095). Cytosol is the expected localization for Hsp90. Supporting Evidence: file:yeast/HSP82/HSP82-deep-research-falcon.md Cytosolic Hsp90 (Hsp82/Hsc82) is broadly distributed during vegetative growth |
| GO:0050821 protein stabilization | IBA GO_REF:0000033 | ACCEPT | Summary: HSP82 stabilizes client proteins as part of its chaperone function. IBA annotation is appropriate. Falcon deep research describes Hsp82 as assisting the late-stage folding, activation, and stability of a defined set of client proteins. Reason: Protein stabilization is a core function of Hsp90. IMP evidence shows HSP82 is required for protein maturation (PMID:27068472). UniProt states it "promotes the maturation, structural maintenance and proper regulation of specific target proteins." Supporting Evidence: file:yeast/HSP82/HSP82-deep-research-falcon.md Hsp82 (Hsp90) is an **ATP-dependent molecular chaperone** that assists the **late-stage folding, activation, and stability** of a large set of specific |
| GO:0034605 cellular response to heat | IBA GO_REF:0000033 | ACCEPT | Summary: HSP82 is the heat-inducible Hsp90 isoform, centrally involved in heat stress response. Falcon deep research provides quantitative support: Hsp82 is very low at 25-30C and induced at 37C to levels similar to the constitutive Hsc82 paralog, and Hsp82 is more thermally stable than Hsc82 (Tm ~60.4C vs 57.1C), consistent with a stress-specialized role. Reason: HSP82 is named as a heat shock protein precisely because it is induced by heat stress. UniProt confirms it is "required for growth at high temperatures" (PMID:2674684). The gene name itself (HSP82 = Heat Shock Protein 82) reflects this core function. Supporting Evidence: file:yeast/HSP82/HSP82-deep-research-falcon.md **Hsp82 is very low at 25–30°C and induced at 37°C to levels similar to Hsc82**, consistent with a stress-specialized role file:yeast/HSP82/HSP82-deep-research-falcon.md Hsp82 is **more thermally stable** than Hsc82 (Tm ~60.4°C vs 57.1°C) |
| GO:0051082 unfolded protein binding | IBA GO_REF:0000033 | MODIFY | Summary: GO:0051082 is now formally obsolete (go-ontology#30962). HSP82 does interact with unfolded/misfolded client proteins but its mechanism is better captured by GO:0140662 (ATP-dependent protein folding chaperone). Reason: GO:0051082 is now formally obsolete (go-ontology#30962). HSP82 is an ATP-dependent foldase; while it does bind unfolded/non-native proteins as part of its chaperone cycle, the binding is coupled to ATP-driven conformational changes. The more appropriate term is GO:0140662 "ATP-dependent protein folding chaperone" which captures both the binding and the active folding mechanism. IDA evidence from PMID:10564510 demonstrated binding to denatured substrates, but this is part of the broader chaperone activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000163527 · PAINT Hsp90 family node SUPPORTS TRANSFER The ancestral assertion captures genuine non-native-client binding, but the now formally obsolete binding term (go-ontology#30962) should be replaced by the ATP-dependent chaperone activity term. Proposed replacements: ATP-dependent protein folding chaperone |
| GO:0048471 perinuclear region of cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The IBA places conserved Hsp90 activity in the perinuclear cytoplasm. HSP82 is principally cytosolic, so any perinuclear enrichment is a secondary spatial context. Reason: The PAINT assertion reflects a curated ancestral-node placement supported by multiple descendants, and there is no HSP82-specific evidence of localization loss or divergence. Retain it as non-core while noting that the retrieved target literature does not independently establish enrichment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000163629 · PAINT Hsp90 family node SUPPORTS TRANSFER The ancestral localization is defensible for a mobile cytosolic Hsp90, and there is no evidence of target-specific loss; direct HSP82 imaging would still be needed to establish enrichment. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | MODIFY | Summary: IEA annotation from UniProt keyword mapping. True but too broad relative to ATP binding and ATPase-cycle annotations. Reason: HSP82 binds ATP through the conserved Hsp90 nucleotide-binding domain; generic nucleotide binding is accurate but less informative than ATP binding for this gene product. Replace the broad parent with ATP binding, while retaining ATP hydrolysis activity as the catalytic-cycle term. Proposed replacements: ATP binding |
| GO:0000492 box C/D snoRNP assembly | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA machine learning prediction for snoRNP assembly involvement. Supported by IMP evidence. Reason: Supported by IMP evidence (PMID:18268103) which showed Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex activity that regulates snoRNA accumulation. This is a legitimate but secondary function of Hsp90, mediated through its general chaperone role on client proteins in the R2TP pathway. Supporting Evidence: PMID:18268103 Together with the Tah1 cofactor, Hsp90 functions to stabilize Pih1. As a consequence, the chaperone is shown to affect box C/D accumulation and maintenance, especially under stress conditions. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for ATP binding from InterPro/ARBA. Consistent with IBA and experimental evidence. Reason: Redundant with IBA annotation but correct. ATP binding is a core molecular function of HSP82. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation for cytoplasm from UniProt subcellular location mapping. Correct. Reason: Consistent with multiple IDA and HDA evidence for cytoplasmic localization. |
| GO:0006457 protein folding | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for protein folding. Redundant with IBA but correct. Reason: Consistent with IBA and experimental annotations for protein folding involvement. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for ATP hydrolysis activity. Redundant with IBA and IDA but correct. Reason: Consistent with IBA and IDA (PMID:12235160) annotations for ATPase activity. |
| GO:0043248 proteasome assembly | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA prediction for proteasome assembly involvement. Supported by IDA/IMP evidence. Reason: Supported by experimental evidence (IDA and IMP, PMID:12853471). HSP82 assists in proteasome assembly as one of its client-dependent functions. Not a core function of HSP82 per se, but a legitimate downstream consequence of its chaperone activity. Supporting Evidence: PMID:12853471 Herein we report a novel function for Hsp90 in the ATP-dependent assembly of the 26S proteasome. |
| GO:0051082 unfolded protein binding | IEA GO_REF:0000120 | MODIFY | Summary: IEA annotation for unfolded protein binding. Same issue as the IBA annotation: the term is now formally obsolete (go-ontology#30962). Reason: GO:0051082 is now formally obsolete (go-ontology#30962). It should be replaced with GO:0140662 "ATP-dependent protein folding chaperone" which better captures the active chaperone mechanism. Proposed replacements: ATP-dependent protein folding chaperone |
| GO:0140662 ATP-dependent protein folding chaperone | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro for ATP-dependent protein folding chaperone. This is the correct and most informative molecular function term for HSP82. Falcon deep research describes Hsp82 as a dimeric chaperone cycling between an open (C-terminally dimerized) state and an ATP-induced closed state with additional N-terminal contacts. Reason: GO:0140662 is the ideal molecular function term for HSP82/Hsp90. It captures both the ATP dependence and the protein folding chaperone activity. HSP82 binds to client proteins and assists their folding through an ATP-dependent conformational cycle. This should be considered the primary MF annotation for HSP82. Supporting Evidence: file:yeast/HSP82/HSP82-deep-research-falcon.md Yeast Hsp90 (Hsp82/Hsc82) is a **dimeric** chaperone cycling between file:yeast/HSP82/HSP82-deep-research-falcon.md an **ATP-induced closed** state with additional N-terminal contacts |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | MARK AS OVER ANNOTATED | Summary: IPI from large-scale mass spectrometry study. Uninformative "protein binding" annotation. Reason: "Protein binding" is uninformative for a molecular chaperone that by definition binds many proteins. HSP82 interacts with dozens of co-chaperones and client proteins. The more informative annotation is GO:0140662 (ATP-dependent protein folding chaperone). Large-scale interaction studies produce many IPI annotations that do not capture specific molecular functions. |
| GO:0005515 protein binding | IPI PMID:12604615 Aha1 binds to the middle domain of Hsp90, contributes to cli... | MARK AS OVER ANNOTATED | Summary: IPI from study of Aha1 binding to Hsp90. Specific interaction with co-chaperone. Reason: While the interaction with Aha1 is genuine and important for the chaperone cycle, "protein binding" is uninformative. The chaperone function is better captured by GO:0140662. |
| GO:0005515 protein binding | IPI PMID:14729968 The ctf13-30/CTF13 genomic haploinsufficiency modifier scree... | MARK AS OVER ANNOTATED | Summary: IPI from ctf13/RSC study. Generic protein binding annotation. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:15102838 A novel mode of chaperone action: heme activation of Hap1 by... | MARK AS OVER ANNOTATED | Summary: IPI from Hap1 interaction study. HSP82 interacts with the transcription factor Hap1. Reason: While HSP82-Hap1 interaction is genuine, "protein binding" is uninformative for a chaperone. |
| GO:0005515 protein binding | IPI PMID:15766533 Navigating the chaperone network: an integrative map of phys... | MARK AS OVER ANNOTATED | Summary: IPI from large-scale chaperone network study (Zhao et al 2005). Many interactions detected. Reason: Large-scale study detecting many chaperone-client and chaperone-cochaperone interactions. "Protein binding" is uninformative for a chaperone. |
| GO:0005515 protein binding | IPI PMID:15879519 A two-hybrid screen of the yeast proteome for Hsp90 interact... | MARK AS OVER ANNOTATED | Summary: IPI from yeast two-hybrid screen for Hsp90 interactors. Reason: Uninformative "protein binding" for a chaperone with extensive interaction network. |
| GO:0005515 protein binding | IPI PMID:16407978 The phosphatase Ppt1 is a dedicated regulator of the molecul... | MARK AS OVER ANNOTATED | Summary: IPI from Ppt1 phosphatase study. Ppt1 is a dedicated regulator of Hsp90. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | MARK AS OVER ANNOTATED | Summary: IPI from proteome survey. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | MARK AS OVER ANNOTATED | Summary: IPI from large-scale protein complex study (Krogan et al 2006). Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:16625188 Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed cha... | MARK AS OVER ANNOTATED | Summary: IPI from crystal structure of HSP82-SBA1-nucleotide complex. Reason: While the SBA1 interaction is structurally characterized, "protein binding" is uninformative. |
| GO:0005515 protein binding | IPI PMID:18268103 Molecular chaperone Hsp90 stabilizes Pih1/Nop17 to maintain ... | MARK AS OVER ANNOTATED | Summary: IPI from R2TP complex/snoRNP assembly study. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | MARK AS OVER ANNOTATED | Summary: IPI from high-quality binary interaction map. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:18818696 Structural and functional coupling of Hsp90- and Sgt1-centre... | MARK AS OVER ANNOTATED | Summary: IPI from Sgt1 complex study. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:18833289 Structural and functional analysis of SGT1-HSP90 core comple... | MARK AS OVER ANNOTATED | Summary: IPI from protein interaction study. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:19536198 An atlas of chaperone-protein interactions in Saccharomyces ... | MARK AS OVER ANNOTATED | Summary: IPI from atlas of chaperone-protein interactions. Reason: Uninformative "protein binding" for a chaperone. This study itself maps the chaperone interaction network. |
| GO:0005515 protein binding | IPI PMID:21170051 Mixed Hsp90-cochaperone complexes are important for the prog... | MARK AS OVER ANNOTATED | Summary: IPI from mixed Hsp90-cochaperone complex study. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:21734642 Combinatorial depletion analysis to assemble the network arc... | MARK AS OVER ANNOTATED | Summary: IPI from SAGA/ADA complex study. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:21892170 Structural analysis of the interaction between Hsp90 and the... | MARK AS OVER ANNOTATED | Summary: IPI from structural analysis of Hsp90-p53 interaction. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:23217712 CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abund... | MARK AS OVER ANNOTATED | Summary: IPI from CDK-dependent Hsp70 phosphorylation study. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:23396352 Integration of the accelerator Aha1 in the Hsp90 co-chaperon... | MARK AS OVER ANNOTATED | Summary: IPI from Aha1 integration into Hsp90 co-chaperone cycle study. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:24012479 High-resolution structural analysis shows how Tah1 tethers H... | MARK AS OVER ANNOTATED | Summary: IPI from protein interaction study. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:24794838 Structural basis for phosphorylation-dependent recruitment o... | MARK AS OVER ANNOTATED | Summary: IPI from Tel2-Hsp90-Pih1 structural study. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:31454312 The role of structural pleiotropy and regulatory evolution i... | MARK AS OVER ANNOTATED | Summary: IPI from structural pleiotropy study of Hsp90 paralogs. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | MARK AS OVER ANNOTATED | Summary: IPI from yeast protein interactome architecture study. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0005515 protein binding | IPI PMID:9817749 In vivo function of Hsp90 is dependent on ATP binding and AT... | MARK AS OVER ANNOTATED | Summary: IPI from study showing Hsp90 function depends on ATP binding and hydrolysis. Reason: Uninformative "protein binding" for a chaperone. The actual finding is about ATP-dependent chaperone function, not generic protein binding. |
| GO:0005515 protein binding | IPI PMID:9819422 Cns1 is an essential protein associated with the hsp90 chape... | MARK AS OVER ANNOTATED | Summary: IPI from Cns1/CPR7 interaction study. Reason: Uninformative "protein binding" for a chaperone. |
| GO:0042802 identical protein binding | IPI PMID:16625188 Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed cha... | ACCEPT | Summary: HSP82 forms homodimers as part of its functional cycle. The crystal structure (PDB:2CG9) confirms dimerization. Falcon deep research describes yeast Hsp90 as a dimeric chaperone whose open state is C-terminally dimerized, with the conserved co-chaperone-binding motif at the C-terminus. Reason: Homodimerization is essential for Hsp90 function. The crystal structure of the closed chaperone complex (PMID:16625188) directly shows the dimer. This is a core structural feature of Hsp90. Supporting Evidence: file:yeast/HSP82/HSP82-deep-research-falcon.md an **open** state (C-terminally dimerized) and file:yeast/HSP82/HSP82-deep-research-falcon.md **C-terminal dimerization domain** including the conserved co-chaperone-binding motif at the C-terminus |
| GO:0042802 identical protein binding | IPI PMID:18268103 Molecular chaperone Hsp90 stabilizes Pih1/Nop17 to maintain ... | ACCEPT | Summary: Additional evidence for HSP82 homodimerization. Reason: Consistent with known Hsp90 dimerization. Duplicate annotation with different reference is fine. Supporting Evidence: PMID:18268103 Hsp82 eluted at the position of a dimer, whereas Tah1 and Pih1 eluted as monomers. |
| GO:0042802 identical protein binding | IPI PMID:19696785 Hsp90 is regulated by a switch point in the C-terminal domai... | ACCEPT | Summary: HSP82 homodimerization via C-terminal domain switch point study. Reason: C-terminal domain dimerization dynamics are important for the conformational cycle. Mutagenesis of A577 modulates dimerization, ATPase, and client activation. |
| GO:0042802 identical protein binding | IPI PMID:20736353 Dynamics of heat shock protein 90 C-terminal dimerization is... | ACCEPT | Summary: HSP82 C-terminal dimerization dynamics study. Reason: Further confirmation of homodimerization as essential for the conformational cycle. |
| GO:0042802 identical protein binding | IPI PMID:23396352 Integration of the accelerator Aha1 in the Hsp90 co-chaperon... | ACCEPT | Summary: HSP82 homodimerization in context of Aha1 co-chaperone cycle. Reason: Consistent with known Hsp90 dimerization. |
| GO:0042802 identical protein binding | IPI PMID:24794838 Structural basis for phosphorylation-dependent recruitment o... | ACCEPT | Summary: HSP82 homodimerization in Tel2-Hsp90-Pih1 study. Reason: Consistent with known Hsp90 dimerization. |
| GO:0042802 identical protein binding | IPI PMID:31454312 The role of structural pleiotropy and regulatory evolution i... | ACCEPT | Summary: HSP82 homodimerization in paralog heteromer study. Reason: The study's interaction dataset supports self-association, and independent direct size-exclusion evidence confirms that purified Hsp82 is dimeric. The paralog study also addresses HSP82-HSC82 heteromer retention, which is distinct from this identical-protein-binding annotation. Supporting Evidence: PMID:18268103 Hsp82 eluted at the position of a dimer, whereas Tah1 and Pih1 eluted as monomers. |
| GO:0070482 response to oxygen levels | NAS PMID:9632766 Molecular mechanism governing heme signaling in yeast: a hig... | KEEP AS NON CORE | Summary: NAS annotation from ComplexPortal, based on HSP82 involvement in HAP1-mediated heme signaling. Reason: HSP82 forms a complex with HAP1, a transcriptional activator regulated by heme (proxy for oxygen). This is a client-dependent function. The NAS evidence is weak but the underlying biology is supported by UniProt documentation of HSP82-HAP1 interaction (PMID:9632766). Supporting Evidence: PMID:9632766 Our data suggest that this complex contains HAP1 and four other cellular proteins including Hsp82 and Ydj1. |
| GO:0005634 nucleus | IDA PMID:32920053 A Single Site Phosphorylation on Hsp82 Ensures Cell Survival... | KEEP AS NON CORE | Summary: IDA evidence for nuclear localization from starvation phosphorylation study. Falcon deep research reinforces a condition-dependent nuclear pool: Hsp90 (with the co-chaperone Sba1/p23) accumulates in the nucleus in quiescent cells (glucose exhaustion) and in sporulating diploids, where nuclear accumulation defects correlate with sporulation/spore-wall defects. Reason: HSP82 is primarily cytoplasmic but a nuclear pool exists, enhanced during starvation, quiescence, and sporulation. The starvation study (PMID:32920053) showed phosphorylation-dependent nuclear localization, and falcon deep research corroborates condition-dependent nuclear accumulation (Tapia & Morano 2010). Nuclear localization remains a regulated, non-core compartment rather than the primary site of action. Supporting Evidence: PMID:32920053 Furthermore, we found that Ppt1 regulates Hsp82 distribution in the cytoplasm and nucleus by dephosphorylating the S485 residue on Hsp82. file:yeast/HSP82/HSP82-deep-research-falcon.md **accumulates in the nucleus in quiescent cells (glucose exhaustion)** and in sporulating diploids |
| GO:0005737 cytoplasm | IDA PMID:32920053 A Single Site Phosphorylation on Hsp82 Ensures Cell Survival... | ACCEPT | Summary: IDA evidence for cytoplasmic localization. Reason: Core localization of HSP82. Consistent with multiple lines of evidence. |
| GO:0016887 ATP hydrolysis activity | IDA PMID:12235160 N-terminal residues regulate the catalytic efficiency of the... | ACCEPT | Summary: Direct assay evidence for ATPase activity of HSP82. Reason: Core molecular function. Direct biochemical analysis showed that Hsp90 variants are impaired in ATP hydrolysis without losing nucleotide binding. Supporting Evidence: PMID:12235160 We show that N-terminal deletion variants of Hsp90 are severely impaired in their ability to hydrolyze ATP. However, nucleotide binding of these constructs is similar to that of the wild type protein. |
| GO:0016887 ATP hydrolysis activity | IMP PMID:27068472 Systematic Mutant Analyses Elucidate General and Client-Spec... | ACCEPT | Summary: Mutant phenotype evidence for ATPase activity from systematic mutant analysis. Reason: Systematic mutational analysis of the ATPase domain linked residues near ATP phosphates to yeast growth and showed client-specific effects on v-Src and glucocorticoid-receptor activation. This complements the direct biochemical ATPase evidence without implying that every client uses an identical mechanism. Supporting Evidence: PMID:27068472 The sensitivity of a position to mutation was strongly influenced by proximity to the phosphates of ATP, indicating that ATPase-driven conformational changes impose stringent physical constraints on Hsp90. |
| GO:0005737 cytoplasm | HDA PMID:11914276 Subcellular localization of the yeast proteome. | ACCEPT | Summary: High-throughput data for cytoplasmic localization. Reason: Consistent with IDA evidence. |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: High-throughput GFP localization data confirming cytoplasm. Reason: Global protein localization study. Consistent with IDA evidence. |
| GO:0005737 cytoplasm | IDA PMID:27385335 Detection of protein-protein interactions at the septin coll... | ACCEPT | Summary: Direct GFP imaging shows Hsp82 in the cytosol, supporting the imported cytoplasm annotation. Reason: GFP imaging of Hsp82 expressed from its endogenous locus directly showed a prominent cytosolic distribution. Cytoplasm is a valid broader parent term, and Hsp82 served as an abundant cytosolic negative control for septin interactions. Supporting Evidence: PMID:27385335 Each of these candidates (Cdc19, Gpp1, Hsp82, Pgk1, and Tpi1), when expressed as a C-terminally GFP-tagged derivative from its endogenous promoter at its native chromosomal locus, exhibited a very prominent cytosolic distribution |
| GO:0051604 protein maturation | IMP PMID:27068472 Systematic Mutant Analyses Elucidate General and Client-Spec... | ACCEPT | Summary: IMP evidence from systematic mutant analysis showing HSP82 is required for protein maturation. Reason: UniProt describes HSP82 as promoting "the maturation, structural maintenance and proper regulation of specific target proteins." Protein maturation is a core function of Hsp90. |
| GO:0000492 box C/D snoRNP assembly | IMP PMID:18268103 Molecular chaperone Hsp90 stabilizes Pih1/Nop17 to maintain ... | KEEP AS NON CORE | Summary: IMP evidence showing Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex for snoRNP assembly. Reason: Hsp90 acts on the R2TP pathway components (Pih1, Tah1) that are required for snoRNP assembly. This is a legitimate client-dependent function but not a core function of HSP82. Supporting Evidence: PMID:18268103 Together with the Tah1 cofactor, Hsp90 functions to stabilize Pih1. As a consequence, the chaperone is shown to affect box C/D accumulation and maintenance, especially under stress conditions. |
| GO:0006458 'de novo' protein folding | IDA PMID:10564510 Contribution of N- and C-terminal domains to the function of... | MODIFY | Summary: PMID:10564510 directly supports non-native-client binding and maturation of selected signaling clients, but not a general de novo-folding role. Reason: The study concerns cofactor-regulated maturation of Hsp90 substrates. Its evidence is better captured by the broader protein-folding process, paired with ATP-dependent protein folding chaperone activity, than by a de novo-folding annotation. Proposed replacements: protein folding Supporting Evidence: file:yeast/HSP82/HSP82-deep-research-falcon.md Hsp82 (Hsp90) is an **ATP-dependent molecular chaperone** that assists the **late-stage folding, activation, and stability** of a large set of specific “client” proteins (substrates), including many signaling regulators (notably protein kinases and transcription factors). |
| GO:0006458 'de novo' protein folding | IMP PMID:9371781 In vivo functions of the Saccharomyces cerevisiae Hsp90 chap... | MODIFY | Summary: Mutant evidence shows that Hsp90 supports folding of a restricted difficult-client subset, not a general de novo-folding role. Reason: Mutant analysis showed that Hsp90 is required for the subset of proteins that have difficulty reaching native conformations, rather than for de novo folding of most proteins. Replace the overly specific imported process with protein folding, which captures selective client folding. Proposed replacements: protein folding Supporting Evidence: PMID:9371781 The data suggest that Hsp90 is not required for the de novo folding of most proteins, but it is required for a specific subset of proteins that have greater difficulty reaching their native conformations. |
| GO:0006970 response to osmotic stress | IMP PMID:16487343 The molecular chaperone Hsp90 is required for high osmotic s... | KEEP AS NON CORE | Summary: IMP evidence showing Hsp90 is required for high osmotic stress response. Reason: Hsp90 is required for adaptation to high osmolarity through a Cdc37-dependent pathway parallel to, rather than within, the canonical HOG pathway. This is a legitimate conditional phenotype but secondary to the core chaperone activity. Supporting Evidence: PMID:16487343 Hsp90 is shown to be required for proper adaptation to high osmolarity via a novel signal transduction pathway that operates parallel to the HOG pathway and requires Cdc37p. |
| GO:0032212 positive regulation of telomere maintenance via telomerase | IDA PMID:17954556 The hsp90 molecular chaperone modulates multiple telomerase ... | KEEP AS NON CORE | Summary: IDA evidence for positive regulation of telomere maintenance via telomerase. Reason: Hsp90 modulates multiple telomerase activities. This is a client-dependent function where Hsp90 chaperones telomerase components. Not a core function of HSP82 itself. Supporting Evidence: PMID:17954556 We have found that the yeast Hsp90 homolog Hsp82p promotes both telomerase DNA binding and nucleotide addition properties. |
| GO:0032212 positive regulation of telomere maintenance via telomerase | IMP PMID:17954556 The hsp90 molecular chaperone modulates multiple telomerase ... | KEEP AS NON CORE | Summary: IMP evidence for telomerase regulation. Reason: Complements IDA evidence. Client-dependent function. Supporting Evidence: PMID:17954556 Importantly, telomere length and telomerase telomere occupancy was yeast Hsp90 dependent. |
| GO:0042026 protein refolding | IMP PMID:9371781 In vivo functions of the Saccharomyces cerevisiae Hsp90 chap... | ACCEPT | Summary: IMP evidence for protein refolding activity from in vivo function study. Reason: Protein refolding is a core chaperone function for selected damaged clients rather than a general capacity to reactivate every heat-damaged protein. The in vivo mutant study demonstrated enhanced reactivation of a heat-damaged substrate. Supporting Evidence: PMID:9371781 Under conditions of stress, Hsp90 does not generally protect proteins from thermal inactivation but does enhance the rate at which a heat-damaged protein is reactivated. |
| GO:0043248 proteasome assembly | IDA PMID:12853471 The molecular chaperone Hsp90 plays a role in the assembly a... | KEEP AS NON CORE | Summary: IDA evidence for proteasome assembly involvement. Reason: HSP82 assists in proteasome assembly as a client-dependent function. The chaperone assists proteasome maturation but this is secondary to its core function. Supporting Evidence: PMID:12853471 Herein we report a novel function for Hsp90 in the ATP-dependent assembly of the 26S proteasome. |
| GO:0043248 proteasome assembly | IMP PMID:12853471 The molecular chaperone Hsp90 plays a role in the assembly a... | KEEP AS NON CORE | Summary: IMP evidence for proteasome assembly. Reason: Complements IDA evidence. Client-dependent function. Supporting Evidence: PMID:12853471 Functional loss of Hsp90 using a temperature-sensitive mutant in yeast caused dissociation of the 26S proteasome. |
| GO:0051082 unfolded protein binding | IDA PMID:10564510 Contribution of N- and C-terminal domains to the function of... | MODIFY | Summary: IDA evidence showing HSP82 binds unfolded/denatured proteins. The imported term is now formally obsolete (go-ontology#30962). Reason: While the experimental evidence is solid (HSP82 does bind unfolded proteins as shown by PMID:10564510), GO:0051082 is now formally obsolete (go-ontology#30962). The binding of unfolded proteins is part of the ATP-dependent chaperone mechanism, better captured by GO:0140662 "ATP-dependent protein folding chaperone." Proposed replacements: ATP-dependent protein folding chaperone |
| GO:0032204 regulation of telomere maintenance | IMP PMID:21829731 HSP90 controls SIR2 mediated gene silencing. | KEEP AS NON CORE | Summary: IMP evidence from CACAO annotation showing HSP90 controls SIR2-mediated gene silencing and telomere maintenance. Reason: HSP90 controls SIR2-mediated gene silencing which affects telomere maintenance. This is another example of a client-dependent function. Secondary to core chaperone activity. |
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Download this section (compressed HTML)Q: Which client proteins (kinases, transcription factors, ribosome assembly factors) most strongly depend on HSP82 nucleotide-state transitions, and how do conformational dwell times map to client maturation efficiency?
Q: How does the HSP82/HSC82 paralog ratio shift the chaperone interactome composition (co-chaperones, clients) under heat versus standard growth, and what fraction of clients are paralog-specific?
Q: What role does single-site phosphorylation (e.g., starvation-dependent) play in compartment-specific HSP82 localization (nucleus vs cytoplasm) and client engagement?
Experiment: Deplete or inhibit HSP82 (e.g., temperature-sensitive alleles, radicicol) and use AP-MS to map condition-dependent client losses, comparing standard growth to heat shock and starvation conditions to dissect core vs. stress-specific clientele.
Experiment: Reconstitute the full Hsp82 conformational cycle in vitro with purified HSP82 dimers, ATP, and a panel of co-chaperones (Sti1, Aha1, Sba1, Cdc37, Cpr6/7, Cns1) plus a model client kinase, and use single-molecule FRET to measure ATP-dependent open/closed dwell times.
Experiment: Generate separation-of-function HSP82 alleles that selectively impair ATPase, dimerization, or co-chaperone binding (using systematic mutagenesis of the M-domain) and measure client-specific phenotypes (e.g., HAP1, telomerase, R2TP, proteasome) to dissect contributions to each downstream pathway.
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