id: P15108
gene_symbol: HSC82
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: >-
  HSC82 encodes the constitutive cytosolic Hsp90 isoform in S. cerevisiae, an ATP-dependent protein folding
  chaperone that acts through ATP binding, ATP hydrolysis, and regulated conformational cycling to mature
  and stabilize selected client proteins. Hsc82 functions as an Hsp90 dimer and engages co-chaperones
  such as Sti1, Cpr6/Cpr7, Sba1/p23, Aha1, Cdc37, Sse1, and Sgt1. It is cytosolic under core conditions,
  contributes to elevated-temperature fitness despite being less heat-inducible than HSP82, and supports
  client pathways including calcineurin, kinase/signaling clients, telomerase, R2TP/snoRNP, and proteasome
  assembly. Broad terms such as generic nucleotide binding, generic protein-containing complex, and unfolded
  protein binding are less informative than ATP-focused Hsp90 chaperone terms.
existing_annotations:
# ============================================================================
# IBA ANNOTATIONS
# ============================================================================
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HSC82/Hsp90 is a well-established protein folding chaperone. IBA annotation is consistent with the
      known function of this conserved chaperone family across eukaryotes.
    action: ACCEPT
    reason: >-
      Protein folding is a core biological process for Hsp90. UniProt describes HSC82 as an "ATP-dependent
      molecular chaperone" that promotes maturation and regulation of client proteins. IMP evidence from
      PMID:7791797 confirms involvement in protein folding.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsp90/Hsc82 functions as an ATP-dependent folding chaperone for late
        intermediates/clients, and specific Hsp90 mutants that disrupt client
        loading/closing/reopening cause client-specific maturation defects and temperature-sensitive
        growth.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HSC82 has well-characterized ATPase activity essential for its chaperone cycle. IBA annotation is
      correct.
    action: ACCEPT
    reason: >-
      ATPase activity is fundamental to Hsp90 function. Directly demonstrated by IDA (PMID:18492664).
      UniProt documents the ATP binding and hydrolysis mechanism.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: 'N-terminal ATP-binding domain; ATP binding drives lid closure and N-terminal association;
        Hsc82 shows higher ATPase activity than Hsp82 at 30–37°C'
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Aha1 and Cpr6 stimulate ATPase activity of both isoforms, while Cdc37,
        Sba1/p23, and Sti1 inhibit with only minor isoform-specific differences.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HSC82 forms Hsp90 dimers and multiple co-chaperone/client complexes, but the generic protein-containing
      complex term is not very informative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Hsc82 participates in many complexes as an Hsp90 chaperone, but GO:0032991 does not identify the
      biologically meaningful assembly. The evidence is better represented by Hsp90 dimer/co-chaperone/client
      complex context together with ATP-dependent protein folding chaperone activity.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsc82 forms many complexes, but specific complexes (homodimer;
        Sti1/Cpr6/Sba1/Cdc37/Sgt1 complexes) are more biologically useful than a generic complex
        term
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Constitutive C-terminal dimerization is central to Hsp90 architecture;
        nucleotide binding promotes transient N-terminal dimerization during the cycle
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      IBA annotation for plasma membrane localization. HSC82 is primarily cytoplasmic but plasma membrane
      association has some HDA support (PMID:16622836).
    action: KEEP_AS_NON_CORE
    reason: >-
      HSC82 is primarily cytoplasmic. Plasma membrane localization is supported by HDA from PMID:16622836
      (plasma membrane proteome study) but is not a core localization. A minor membrane-associated pool
      is plausible.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: No direct Hsc82 localization evidence in the retrieved sources
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HSC82 binds ATP as part of its chaperone cycle. Well-established by crystallography of Hsp90 orthologs.
    action: ACCEPT
    reason: >-
      ATP binding is essential for Hsp90 function. The N-terminal domain contains the Bergerat ATP-binding
      fold. UniProt documents the ATP binding site residues.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: 'N-terminal ATP-binding domain; ATP binding drives lid closure and N-terminal association;
        Hsc82 shows higher ATPase activity than Hsp82 at 30–37°C'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HSC82 is a cytosolic protein. IBA annotation is correct.
    action: ACCEPT
    reason: >-
      Consistent with HDA evidence for cytoplasm localization (PMID:14562095). Cytosol is the expected
      primary localization for Hsp90.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsc82 is described as the constitutive cytosolic Hsp90 isoform; many
        experimental Hsc82 interactome/purification studies use cytosolic lysates, consistent with
        CC:cytosol annotations for both isoforms, with expression-level differences for HSC82 vs
        HSP82.
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HSC82 stabilizes client proteins as part of its chaperone function. IBA annotation is appropriate.
    action: ACCEPT
    reason: >-
      Protein stabilization is a core function of Hsp90. UniProt describes the role of HSC82 in stabilizing
      calcineurin (CNA2) under salt stress (PMID:11094077).
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Supports stability and activation of diverse clients; proteome analyses and
        mutant studies show client-specific maturation defects and reduced abundance of client
        subsets when cycle steps are disrupted
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Direct Hsc82 binding to CNB1 and effects on CNA2/CNB1 complex state/activity
        support calcineurin as an Hsp90 client/regulatory target
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Although HSC82 is the constitutive isoform, it is still involved in heat stress response.
    action: ACCEPT
    reason: >-
      IMP evidence from PMID:2674684 confirms that both HSP82 and HSC82 are required for growth at
      elevated temperatures. While HSC82 is constitutively expressed, it still contributes to
      thermal tolerance.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsc82 mutants show 37°C growth defects, while Hsp82 is more thermally
        stable/refolds better under stress
    - reference_id: file:yeast/HSC82/HSC82-uniprot.txt
      supporting_text: for growth at high temperatures.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GO:0051082 is proposed for obsoletion. HSC82 does interact with unfolded/misfolded client proteins
      but its mechanism is better captured by GO:0140662 (ATP-dependent protein folding chaperone).
    action: MODIFY
    reason: >-
      GO:0051082 is proposed for obsoletion. HSC82 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:9465043 demonstrated binding to denatured substrates, but this is part of the broader
      chaperone activity.
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsp90/Hsc82 is better captured by ATP-dependent chaperone cycle terms;
        mechanistic descriptions emphasize action on partially folded/late intermediates and
        cochaperone-regulated cycle steps rather than generic unfolded-substrate binding.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      IBA perinuclear localization inference. HSC82 is primarily cytosolic, and Falcon did not retrieve
      direct Hsc82-specific perinuclear localization evidence.
    action: UNDECIDED
    reason: >-
      The annotation may reflect ortholog or context-specific localization, but the accessible HSC82 evidence
      supports cytosol as the core localization and does not provide direct Hsc82-specific support for
      perinuclear enrichment. Leave undecided pending direct localization evidence.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: No direct Hsc82 localization evidence in the retrieved sources
# ============================================================================
# IEA ANNOTATIONS
# ============================================================================
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      IEA annotation from UniProt keyword mapping. True but too broad relative to ATP binding and ATPase-cycle
      annotations.
    action: MODIFY
    reason: >-
      HSC82 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 keeping ATP hydrolysis activity as the catalytic cycle term.
    proposed_replacement_terms:
    - id: GO:0005524
      label: ATP binding
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: True but much less informative than ATP binding/ATPase activity; GO should
        prefer the specific ATP-related terms
- term:
    id: GO:0000492
    label: box C/D snoRNP assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      ARBA machine learning prediction for snoRNP assembly involvement. Supported by IMP evidence.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsp90 network reviews mention Tah1/Pih1 (R2TP-like) functions, but direct
        Hsc82-specific experimental support in the retrieved set is weak
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      IEA annotation for ATP binding. Consistent with IBA and experimental evidence.
    action: ACCEPT
    reason: >-
      Redundant with IBA annotation but correct. ATP binding is a core molecular function of HSC82.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: 'N-terminal ATP-binding domain; ATP binding drives lid closure and N-terminal association;
        Hsc82 shows higher ATPase activity than Hsp82 at 30–37°C'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      IEA annotation for cytoplasm from UniProt subcellular location mapping. Correct.
    action: ACCEPT
    reason: >-
      Consistent with HDA evidence for cytoplasmic localization (PMID:14562095).
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsc82 is described as the constitutive cytosolic Hsp90 isoform; many
        experimental Hsc82 interactome/purification studies use cytosolic lysates, consistent with
        CC:cytosol annotations for both isoforms, with expression-level differences for HSC82 vs
        HSP82.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      IEA annotation for mitochondrial localization from UniProt. Supported by HDA evidence.
    action: KEEP_AS_NON_CORE
    reason: >-
      HSC82 has been detected in mitochondrial proteome studies (PMID:14576278, PMID:16823961). This is
      likely a minor pool; the primary localization is cytoplasmic. Not a core localization.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Some literature discusses cytosolic Hsp90/co-chaperones affecting
        mitochondrial biogenesis or preprotein handling, but that does not establish stable
        mitochondrial localization of Hsc82
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      IEA annotation for protein folding. Redundant with IBA but correct.
    action: ACCEPT
    reason: >-
      Consistent with IBA and experimental annotations for protein folding involvement.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsp90/Hsc82 functions as an ATP-dependent folding chaperone for late
        intermediates/clients, and specific Hsp90 mutants that disrupt client
        loading/closing/reopening cause client-specific maturation defects and temperature-sensitive
        growth.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      IEA annotation for ATP hydrolysis activity. Redundant with IBA and IDA but correct.
    action: ACCEPT
    reason: >-
      Consistent with IBA and IDA (PMID:18492664) annotations for ATPase activity.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: 'N-terminal ATP-binding domain; ATP binding drives lid closure and N-terminal association;
        Hsc82 shows higher ATPase activity than Hsp82 at 30–37°C'
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Aha1 and Cpr6 stimulate ATPase activity of both isoforms, while Cdc37,
        Sba1/p23, and Sti1 inhibit with only minor isoform-specific differences.
- term:
    id: GO:0043248
    label: proteasome assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      ARBA prediction for proteasome assembly involvement. Supported by IMP evidence.
    action: KEEP_AS_NON_CORE
    reason: >-
      Supported by IMP evidence (PMID:12853471). Hsp90 assists in proteasome assembly as one of
      its client-dependent functions. Not a core function of HSC82 per se.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      IEA annotation for unfolded protein binding. Same issue as IBA annotation - term proposed for obsoletion.
    action: MODIFY
    reason: >-
      GO:0051082 is proposed for obsoletion. Should be replaced with GO:0140662 "ATP-dependent
      protein folding chaperone" which better captures the active chaperone mechanism.
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsp90/Hsc82 is better captured by ATP-dependent chaperone cycle terms;
        mechanistic descriptions emphasize action on partially folded/late intermediates and
        cochaperone-regulated cycle steps rather than generic unfolded-substrate binding.
- term:
    id: GO:0140662
    label: ATP-dependent protein folding chaperone
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation from InterPro for ATP-dependent protein folding chaperone. This is the correct
      and most informative molecular function term for HSC82.
    action: ACCEPT
    reason: >-
      GO:0140662 is the ideal molecular function term for HSC82/Hsp90. It captures both the ATP
      dependence and the protein folding chaperone activity. This should be considered the primary
      MF annotation for HSC82.
# ============================================================================
# IPI PROTEIN BINDING ANNOTATIONS
# ============================================================================
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsp90/Hsc82 functions as an ATP-dependent folding chaperone for late
        intermediates/clients, and specific Hsp90 mutants that disrupt client
        loading/closing/reopening cause client-specific maturation defects and temperature-sensitive
        growth.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11805826
  review:
    summary: >-
      IPI from large-scale protein complex study. Uninformative "protein binding" annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Protein binding" is uninformative for a molecular chaperone that by definition binds many
      proteins. The more informative annotation is GO:0140662 (ATP-dependent protein folding chaperone).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11805837
  review:
    summary: >-
      IPI from mass spectrometry study. Uninformative "protein binding" annotation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15699485
  review:
    summary: >-
      IPI from polyubiquitin conjugate study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15766533
  review:
    summary: >-
      IPI from large-scale chaperone network study (Zhao et al 2005).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16429126
  review:
    summary: >-
      IPI from proteome survey.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16554755
  review:
    summary: >-
      IPI from large-scale protein complex study (Krogan et al 2006).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18719252
  review:
    summary: >-
      IPI from high-quality binary interaction map.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19536198
  review:
    summary: >-
      IPI from atlas of chaperone-protein interactions.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21734642
  review:
    summary: >-
      IPI from SAGA/ADA complex study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23217712
  review:
    summary: >-
      IPI from CDK-dependent Hsp70 phosphorylation study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25073740
  review:
    summary: >-
      IPI from protein interaction study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31454312
  review:
    summary: >-
      IPI from structural pleiotropy study of Hsp90 paralogs. Documents HSP82-HSC82 heterodimerization.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      While the HSP82-HSC82 heterodimerization is biologically interesting, "protein binding"
      is uninformative. The heterodimerization could be captured by GO:0042802 (identical protein binding)
      or a more specific term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37070168
  review:
    summary: >-
      IPI from RNA-dependent interactome study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37968396
  review:
    summary: >-
      IPI from yeast protein interactome architecture study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9819421
  review:
    summary: >-
      IPI from Cns1/Hsp90 interaction study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
# ============================================================================
# OTHER EXPERIMENTAL ANNOTATIONS
# ============================================================================
- term:
    id: GO:0070482
    label: response to oxygen levels
  evidence_type: NAS
  original_reference_id: PMID:9632766
  review:
    summary: >-
      NAS annotation based on HSC82 involvement in HAP1-mediated heme signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      HSC82 (like 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 plausible.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsc82 contributes to heat/elevated-temperature fitness and some stress-linked
        client pathways, but very broad stress-response annotations risk conflating constitutive
        Hsc82 with inducible Hsp82
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: HDA
  original_reference_id: PMID:14562095
  review:
    summary: >-
      High-throughput GFP localization data confirming cytoplasm.
    action: ACCEPT
    reason: >-
      Global protein localization study. Core localization of HSC82.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsc82 is described as the constitutive cytosolic Hsp90 isoform; many
        experimental Hsc82 interactome/purification studies use cytosolic lysates, consistent with
        CC:cytosol annotations for both isoforms, with expression-level differences for HSC82 vs
        HSP82.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HDA
  original_reference_id: PMID:14576278
  review:
    summary: >-
      HDA for mitochondrial localization from mitochondrial proteome study.
    action: KEEP_AS_NON_CORE
    reason: >-
      HSC82 was detected in the yeast mitochondrial proteome, suggesting a minor mitochondrial pool.
      Not a primary localization.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Some literature discusses cytosolic Hsp90/co-chaperones affecting
        mitochondrial biogenesis or preprotein handling, but that does not establish stable
        mitochondrial localization of Hsc82
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HDA
  original_reference_id: PMID:16823961
  review:
    summary: >-
      Additional HDA for mitochondrial localization from mitochondrial proteomics.
    action: KEEP_AS_NON_CORE
    reason: >-
      Consistent with PMID:14576278 for a minor mitochondrial pool. Not a core localization.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Some literature discusses cytosolic Hsp90/co-chaperones affecting
        mitochondrial biogenesis or preprotein handling, but that does not establish stable
        mitochondrial localization of Hsc82
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: HDA
  original_reference_id: PMID:16622836
  review:
    summary: >-
      HDA for plasma membrane localization from plasma membrane proteomics study.
    action: KEEP_AS_NON_CORE
    reason: >-
      HSC82 was detected in the plasma membrane proteome, suggesting a minor membrane-associated pool.
      Not a primary localization.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: No direct Hsc82 localization evidence in the retrieved sources
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: IMP
  original_reference_id: PMID:2674684
  review:
    summary: >-
      IMP evidence showing that Hsp90 is essential for growth at elevated temperatures.
    action: ACCEPT
    reason: >-
      Study demonstrated that both HSP82 and HSC82 are required for growth at high temperatures.
      HSC82 is constitutively expressed but still contributes to heat stress tolerance.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsc82 mutants show 37°C growth defects, while Hsp82 is more thermally
        stable/refolds better under stress
    - reference_id: file:yeast/HSC82/HSC82-uniprot.txt
      supporting_text: for growth at high temperatures.
- term:
    id: GO:0000492
    label: box C/D snoRNP assembly
  evidence_type: IMP
  original_reference_id: PMID:18268103
  review:
    summary: >-
      IMP evidence showing Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex for snoRNP assembly.
    action: KEEP_AS_NON_CORE
    reason: >-
      Hsp90 acts on the R2TP pathway components (Pih1, Tah1) that are required for snoRNP assembly.
      Client-dependent function, not core.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsp90 network reviews mention Tah1/Pih1 (R2TP-like) functions, but direct
        Hsc82-specific experimental support in the retrieved set is weak
- term:
    id: GO:0000723
    label: telomere maintenance
  evidence_type: IMP
  original_reference_id: PMID:17954556
  review:
    summary: >-
      IMP evidence showing Hsp90 modulates telomerase activities.
    action: KEEP_AS_NON_CORE
    reason: >-
      Hsp90 chaperones telomerase components. This is a client-dependent function, not a core
      function of HSC82 itself.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IMP
  original_reference_id: PMID:7791797
  review:
    summary: >-
      IMP evidence for protein folding from early characterization study.
    action: ACCEPT
    reason: >-
      Core biological process for HSC82/Hsp90. Directly demonstrates the role in protein folding.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsp90/Hsc82 functions as an ATP-dependent folding chaperone for late
        intermediates/clients, and specific Hsp90 mutants that disrupt client
        loading/closing/reopening cause client-specific maturation defects and temperature-sensitive
        growth.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IDA
  original_reference_id: PMID:18492664
  review:
    summary: >-
      Direct assay evidence for ATPase activity of HSC82. Intra- and intermonomer interactions
      are required for ATP hydrolysis.
    action: ACCEPT
    reason: >-
      Core molecular function. Direct biochemical measurement of ATPase activity showing that both
      intra- and intermonomer interactions synergistically facilitate ATP hydrolysis.
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: 'N-terminal ATP-binding domain; ATP binding drives lid closure and N-terminal association;
        Hsc82 shows higher ATPase activity than Hsp82 at 30–37°C'
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Aha1 and Cpr6 stimulate ATPase activity of both isoforms, while Cdc37,
        Sba1/p23, and Sti1 inhibit with only minor isoform-specific differences.
- term:
    id: GO:0043248
    label: proteasome assembly
  evidence_type: IMP
  original_reference_id: PMID:12853471
  review:
    summary: >-
      IMP evidence for proteasome assembly involvement.
    action: KEEP_AS_NON_CORE
    reason: >-
      HSC82 assists in proteasome assembly as a client-dependent function. Secondary to core
      chaperone activity.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:9465043
  review:
    summary: >-
      IDA evidence for unfolded protein binding. Term proposed for obsoletion.
    action: MODIFY
    reason: >-
      While the experimental evidence is solid (HSC82 does bind unfolded proteins), GO:0051082
      is proposed for obsoletion. The binding of unfolded proteins is part of the ATP-dependent
      chaperone mechanism, better captured by GO:0140662 "ATP-dependent protein folding chaperone."
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
    supported_by:
    - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
      supporting_text: Hsp90/Hsc82 is better captured by ATP-dependent chaperone cycle terms;
        mechanistic descriptions emphasize action on partially folded/late intermediates and
        cochaperone-regulated cycle steps rather than generic unfolded-substrate binding.
core_functions:
- description: >-
    Primary molecular function: ATP-dependent protein folding chaperone. HSC82 binds to
    client proteins and assists their folding through an ATP-dependent conformational cycle.
    Supported by IEA from InterPro, IDA evidence for ATP hydrolysis (PMID:18492664), and
    IDA evidence for unfolded protein binding (PMID:9465043).
  molecular_function:
    id: GO:0140662
    label: ATP-dependent protein folding chaperone
  directly_involved_in:
  - id: GO:0006457
    label: protein folding
  - id: GO:0034605
    label: cellular response to heat
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
    supporting_text: Hsp90/Hsc82 functions as an ATP-dependent folding chaperone for late
      intermediates/clients, and specific Hsp90 mutants that disrupt client
      loading/closing/reopening cause client-specific maturation defects and temperature-sensitive
      growth.
  - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
    supporting_text: 'N-terminal ATP-binding domain; ATP binding drives lid closure and N-terminal association;
      Hsc82 shows higher ATPase activity than Hsp82 at 30–37°C'
  - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
    supporting_text: Supports stability and activation of diverse clients; proteome analyses and
      mutant studies show client-specific maturation defects and reduced abundance of client subsets
      when cycle steps are disrupted
  - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
    supporting_text: Hsc82 is described as the constitutive cytosolic Hsp90 isoform; many
      experimental Hsc82 interactome/purification studies use cytosolic lysates, consistent with
      CC:cytosol annotations for both isoforms, with expression-level differences for HSC82 vs
      HSP82.
- description: >-
    ATPase activity is fundamental to the Hsp90 chaperone cycle. Directly demonstrated by
    IDA (PMID:18492664). Intra- and intermonomer interactions synergistically facilitate
    ATP hydrolysis.
  molecular_function:
    id: GO:0016887
    label: ATP hydrolysis activity
  directly_involved_in:
  - id: GO:0006457
    label: protein folding
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
    supporting_text: 'N-terminal ATP-binding domain; ATP binding drives lid closure and N-terminal association;
      Hsc82 shows higher ATPase activity than Hsp82 at 30–37°C'
  - reference_id: file:yeast/HSC82/HSC82-deep-research-falcon.md
    supporting_text: Aha1 and Cpr6 stimulate ATPase activity of both isoforms, while Cdc37,
      Sba1/p23, and Sti1 inhibit with only minor isoform-specific differences.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings:
  - statement: HSC82 is annotated to GO:0140662 ATP-dependent protein folding chaperone via
      InterPro-to-GO mapping reflecting Hsp90 family membership.
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings:
  - statement: PANTHER phylogenetic-tree annotation propagates conserved Hsp90 chaperone functions
      (ATP binding, ATP hydrolysis, protein folding, cellular response to heat, protein
      stabilization, identical protein binding, cytosol localization) to S. cerevisiae HSC82.
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings:
  - statement: UniProtKB keyword 'Nucleotide-binding' maps to GO:0000166 nucleotide binding for
      HSC82 based on its conserved Hsp90 ATPase domain.
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary
    mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings:
  - statement: HSC82 UniProt subcellular location annotations (cytoplasm, mitochondrion) are mapped
      to corresponding cellular component GO terms.
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings:
  - statement: ARBA machine-learning model assigns HSC82 to box C/D snoRNP assembly and proteasome
      assembly based on Hsp90 family signatures and chaperone client patterns.
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings:
  - statement: Combined automated IEA pipelines annotate HSC82 with ATP binding, ATP hydrolysis
      activity, protein folding, and unfolded protein binding from UniProt features.
- id: PMID:11805826
  title: Functional organization of the yeast proteome by systematic analysis of protein complexes.
  findings:
  - statement: HSC82 was identified in multi-protein complexes by systematic functional organization
      of the yeast proteome.
    supporting_text: Functional organization of the yeast proteome by systematic analysis of protein
      complexes.
    reference_section_type: ABSTRACT
- id: PMID:11805837
  title: Systematic identification of protein complexes in Saccharomyces cerevisiae by mass
    spectrometry.
  findings:
  - statement: HSC82 was identified in multi-protein complexes by systematic affinity-purification
      mass spectrometry.
    supporting_text: Systematic identification of protein complexes in Saccharomyces cerevisiae by
      mass spectrometry.
    reference_section_type: ABSTRACT
- id: PMID:12853471
  title: The molecular chaperone Hsp90 plays a role in the assembly and maintenance of the 26S
    proteasome.
  findings:
  - statement: HSC82/Hsp90 is required for assembly and maintenance of the 26S proteasome in vivo,
      supporting GO:0043248 proteasome assembly as a client-dependent secondary function.
    supporting_text: Herein we report a novel function for Hsp90 in the ATP-dependent assembly of
      the 26S proteasome. Functional loss of Hsp90 using a temperature-sensitive mutant in yeast
      caused dissociation of the 26S proteasome.
    reference_section_type: ABSTRACT
- id: PMID:14562095
  title: Global analysis of protein localization in budding yeast.
  findings:
  - statement: Genome-wide GFP localization study assigns HSC82 to the cytoplasm in S. cerevisiae.
    supporting_text: Global analysis of protein localization in budding yeast.
    reference_section_type: RESULTS
- id: PMID:14576278
  title: The proteome of Saccharomyces cerevisiae mitochondria.
  findings:
  - statement: HSC82 was detected in the yeast mitochondrial proteome, supporting a minor
      mitochondrial pool.
    supporting_text: The proteome of Saccharomyces cerevisiae mitochondria.
    reference_section_type: RESULTS
- id: PMID:15699485
  title: Analysis of polyubiquitin conjugates reveals that the Rpn10 substrate receptor contributes
    to the turnover of multiple proteasome targets.
  findings:
  - statement: HSC82 appears in polyubiquitin conjugate analysis as a Rpn10-relevant proteasome
      substrate context, consistent with chaperone roles in client triage.
    supporting_text: Analysis of polyubiquitin conjugates reveals that the Rpn10 substrate receptor
      contributes to the turnover of multiple proteasome targets.
    reference_section_type: ABSTRACT
- id: PMID:15766533
  title: 'Navigating the chaperone network: an integrative map of physical and genetic interactions mediated
    by the hsp90 chaperone.'
  findings:
  - statement: Integrative map of HSC82/Hsp90 physical and genetic interactions defines its central
      position in the yeast chaperone network.
    supporting_text: 'Navigating the chaperone network: an integrative map of physical and genetic interactions
      mediated by the hsp90 chaperone.'
    reference_section_type: ABSTRACT
- id: PMID:16429126
  title: Proteome survey reveals modularity of the yeast cell machinery.
  findings:
  - statement: Proteome survey of yeast cellular machinery places HSC82 within multi-protein modules
      consistent with its chaperone hub status.
    supporting_text: Proteome survey reveals modularity of the yeast cell machinery.
    reference_section_type: ABSTRACT
- id: PMID:16554755
  title: Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
  findings:
  - statement: HSC82 is part of the global landscape of yeast protein complexes mapped by tandem
      affinity purification.
    supporting_text: Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
    reference_section_type: ABSTRACT
- id: PMID:16622836
  title: The plasma membrane proteome of Saccharomyces cerevisiae and its response to the antifungal
    calcofluor.
  findings:
  - statement: HSC82 was detected in the plasma membrane proteome of S. cerevisiae, supporting a
      minor membrane-associated pool.
    supporting_text: The plasma membrane proteome of Saccharomyces cerevisiae and its response to
      the antifungal calcofluor.
    reference_section_type: RESULTS
- id: PMID:16823961
  title: 'Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for
    mitochondrial proteomics.'
  findings:
  - statement: HSC82 was detected in extended yeast mitochondrial proteomics datasets, consistent
      with a minor mitochondrial pool.
    supporting_text: 'Toward the complete yeast mitochondrial proteome: multidimensional separation techniques
      for mitochondrial proteomics.'
    reference_section_type: ABSTRACT
- id: PMID:17954556
  title: The hsp90 molecular chaperone modulates multiple telomerase activities.
  findings:
  - statement: HSC82/Hsp90 modulates multiple telomerase activities, supporting its role in telomere
      maintenance regulation as a client-dependent function.
    supporting_text: The hsp90 molecular chaperone modulates multiple telomerase activities.
    reference_section_type: ABSTRACT
- id: PMID:18268103
  title: Molecular chaperone Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex activity that
    regulates snoRNA accumulation.
  findings:
  - statement: HSC82/Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex activity that regulates
      snoRNA accumulation, providing IMP evidence for box C/D snoRNP assembly involvement.
    supporting_text: 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.
    reference_section_type: ABSTRACT
- id: PMID:18492664
  title: Intra- and intermonomer interactions are required to synergistically facilitate ATP
    hydrolysis in Hsp90.
  findings:
  - statement: Direct biochemical measurement of ATPase activity showing intra- and intermonomer
      cooperation
    supporting_text: Intra- and intermonomer interactions are required to synergistically facilitate
      ATP hydrolysis in Hsp90.
    reference_section_type: ABSTRACT
- id: PMID:18719252
  title: High-quality binary protein interaction map of the yeast interactome network.
  findings:
  - statement: HSC82 is captured in a high-quality binary interaction map of the yeast interactome.
    supporting_text: High-quality binary protein interaction map of the yeast interactome network.
    reference_section_type: RESULTS
- id: PMID:19536198
  title: 'An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: implications to protein
    folding pathways in the cell.'
  findings:
  - statement: Yeast atlas of chaperone-protein interactions defines HSC82's extensive
      chaperone-client and chaperone-cochaperone interaction network.
    supporting_text: 'An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: implications
      to protein folding pathways in the cell.'
    reference_section_type: ABSTRACT
- id: PMID:21734642
  title: Combinatorial depletion analysis to assemble the network architecture of the SAGA and ADA
    chromatin remodeling complexes.
  findings:
  - statement: HSC82 likely appeared as a background chaperone interactor in affinity-purification
      proteomics of SAGA/ADA; HSC82-specific information appears to be in supplementary data rather
      than the cached main text. This reference underlies the IPI protein-binding annotation and
      supports the MARK_AS_OVER_ANNOTATED decision rather than implying genuine SAGA/ADA membership.
- id: PMID:23217712
  title: CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle
    progression.
  findings:
  - statement: The paper studies CDK-dependent T36 phosphorylation of the yeast Hsp70 Ssa1 (and the
      homologous T38 site of mammalian Hsc70) controlling G1 cyclin (Cln3/Cyclin D1) binding and
      degradation; HSC82 is not the subject of this paper. The IPI annotation likely reflects HSC82
      being captured in Ssa1 interactome MS as part of the broader Hsp70/Hsp90 chaperone network,
      hence the over-annotation classification of the protein binding term.
    supporting_text: 'Here, we show that Ssa1 can be phosphorylated by Cdk1 or Pho85 on T36, a CDK consensus
      site conserved across the Hsp70 family. T36 phosphorylation displaces Ydj1 to allow binding of Cln3,
      leading to its degradation.'
    reference_section_type: INTRODUCTION
- id: PMID:25073740
  title: Molecular architecture and function of the SEA complex, a modulator of the TORC1 pathway.
  findings:
  - statement: HSC82 was detected as an interactor in molecular architecture studies of the SEA
      complex, a TORC1 pathway modulator.
    supporting_text: Molecular architecture and function of the SEA complex, a modulator of the
      TORC1 pathway.
    reference_section_type: ABSTRACT
- id: PMID:2674684
  title: hsp82 is an essential protein that is required in higher concentrations for growth of cells
    at higher temperatures.
  findings:
  - statement: Both HSP82 and HSC82 are required for growth at elevated temperatures
    supporting_text: hsp82 is an essential protein that is required in higher concentrations for
      growth of cells at higher temperatures.
    reference_section_type: ABSTRACT
- id: PMID:31454312
  title: The role of structural pleiotropy and regulatory evolution in the retention of heteromers
    of paralogs.
  findings:
  - statement: Structural pleiotropy and regulatory evolution maintain HSP82-HSC82 paralog
      heteromers, supporting identical protein binding (homo- and heterodimerization).
    supporting_text: The role of structural pleiotropy and regulatory evolution in the retention of
      heteromers of paralogs.
    reference_section_type: ABSTRACT
- id: PMID:37070168
  title: RNA-dependent interactome allows network-based assignment of RNA-binding protein function.
  findings:
  - statement: HSC82 appeared as a prey protein in a quantitative proteomics study mapping
      RNA-dependent interactions for 40 yeast RBPs; specific RDI vs PPI classification for HSC82 is
      in supplementary data not reproduced in the cached text. This reference underlies the IPI
      protein-binding annotation and supports the MARK_AS_OVER_ANNOTATED decision.
- id: PMID:37968396
  title: The social and structural architecture of the yeast protein interactome.
  findings:
  - statement: HSC82 is part of the social/structural architecture of the yeast protein interactome
      captured by integrative network analysis.
    supporting_text: The social and structural architecture of the yeast protein interactome.
    reference_section_type: ABSTRACT
- id: PMID:7791797
  title: 'Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase.'
  findings:
  - statement: Hsp90 is required for protein folding in vivo
    supporting_text: 'Mutational analysis of Hsp90 function: interactions with a steroid receptor and
      a protein kinase.'
    reference_section_type: ABSTRACT
- id: PMID:9465043
  title: Two chaperone sites in Hsp90 differing in substrate specificity and ATP dependence.
  findings:
  - statement: HSC82 binds unfolded proteins
    supporting_text: Two chaperone sites in Hsp90 differing in substrate specificity and ATP
      dependence.
    reference_section_type: ABSTRACT
- id: PMID:9632766
  title: 'Molecular mechanism governing heme signaling in yeast: a higher-order complex mediates heme
    regulation of the transcriptional activator HAP1.'
  findings:
  - statement: The paper identifies Hsp82 (the inducible Hsp90 paralog), not HSC82, as a component
      of a higher-order complex with HAP1 and Ydj1 that mediates heme regulation of HAP1; cited here
      for HSC82 by paralog extrapolation given the high HSP82/HSC82 sequence identity and shared
      client repertoire.
    supporting_text: 'Our data suggest that this complex contains HAP1 and four other cellular proteins
      including Hsp82 and Ydj1.'
    reference_section_type: ABSTRACT
- id: PMID:9819421
  title: CNS1 encodes an essential p60/Sti1 homolog in Saccharomyces cerevisiae that suppresses
    cyclophilin 40 mutations and interacts with Hsp90.
  findings:
  - statement: CNS1 encodes an essential p60/Sti1 homolog that suppresses cyclophilin 40 mutations
      and interacts with HSC82/Hsp90, supporting the cochaperone-network annotations.
    supporting_text: CNS1 encodes an essential p60/Sti1 homolog in Saccharomyces cerevisiae that
      suppresses cyclophilin 40 mutations and interacts with Hsp90.
    reference_section_type: ABSTRACT
- id: PMID:11094077
  title: Role of HSP90 in salt stress tolerance via stabilization and regulation of calcineurin.
  findings:
  - statement: HSC82 stabilizes and regulates calcineurin (CNA2) under salt stress conditions
    supporting_text: Cna2 and Hsc82 coimmunoprecipitated from control cells grown under normal
      conditions but not from stressed cells.
    reference_section_type: ABSTRACT
- id: file:yeast/HSC82/HSC82-deep-research-falcon.md
  title: Falcon deep research report for S. cerevisiae HSC82 GO annotation review
  findings:
  - statement: >-
      Falcon deep research synthesis covering the core HSC82 functions
      (ATP-dependent Hsp90 chaperone cycle, cytosolic localization, client/
      co-chaperone complexes, calcineurin/CNA2 stabilization) and adjudicating
      non-core or questionable annotations (plasma membrane, perinuclear
      region, mitochondrion, generic protein-containing complex/nucleotide
      binding, unfolded protein binding vs. ATP-dependent protein folding
      chaperone, box C/D snoRNP/R2TP, kinetochore/SGT1, broad stress-response
      terms), with explicit distinction from the inducible HSP82 paralog.
- id: file:yeast/HSC82/HSC82-uniprot.txt
  title: UniProtKB record for S. cerevisiae HSC82 (P15108)
  findings:
  - statement: >-
      Reviewed Swiss-Prot entry describing HSC82 as the constitutive cytosolic
      Hsp90 isoform "ATP-dependent molecular chaperone HSC82" (705 aa). Source
      of UniProt-curated cross-references and the IEA mappings (GO_REF:0000043,
      GO_REF:0000044, GO_REF:0000117) used in the GOA file.
suggested_questions:
- question: Under non-stress conditions, which Hsp90 clients are predominantly chaperoned by the
    constitutive HSC82 isoform versus the inducible HSP82, and how does the relative paralog
    abundance shape clientele selection?
- question: What is the functional significance of HSP82-HSC82 heterodimer formation, and is
    heterodimerization required for engagement of specific clients or co-chaperones?
- question: Do mitochondrial and plasma-membrane-associated HSC82 pools have specialized functions
    (e.g., mitochondrial protein import support, membrane raft proteostasis), or do they reflect
    non-functional spillover?
suggested_experiments:
- description: Quantitatively profile co-chaperone occupancy and client maturation efficiency in
    single (hsc82Δ, hsp82Δ) and double-paralog deletion/over-expression strains by AP-MS and Western
    to deconvolve constitutive vs inducible chaperone contributions.
- description: Reconstitute HSP82-HSC82 heterodimers in vitro with purified proteins and a panel of
    co-chaperones (Sti1, Aha1, Sba1, Cdc37) and measure ATPase rates plus client (e.g.,
    glucocorticoid receptor) activation efficiency relative to the homodimers.
- description: Perform proximity-labeling proteomics (TurboID) of HSC82 in mitochondrial and
    plasma-membrane subfractions versus cytosol to test whether minor pools have distinctive
    interactomes.
tags:
- chaperone
- hsp90
- atp-dependent-foldase
- co-chaperone-network