HSP82

id: P02829
gene_symbol: HSP82
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: >-
  HSP82 is the stress-inducible isoform of Hsp90 in S. cerevisiae. It is an ATP-dependent molecular chaperone
  that promotes the maturation, structural maintenance, and proper regulation of specific client proteins,
  particularly those involved in cell cycle control and signal transduction. HSP82 functions as a homodimer,
  undergoing an ATP-dependent conformational cycle that acts as a molecular clamp on client proteins. It interacts
  with a large network of co-chaperones (STI1, AHA1, CDC37, SBA1, CPR6, CPR7, CNS1, SSE1, HCH1) that modulate
  its ATPase cycle and substrate recognition. HSP82 is required for growth at high temperatures.
existing_annotations:
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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 de novo protein folding (PMID:10564510, PMID:9371781).
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HSP82 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:12235160) and
      multiple structural studies showing ATP binding and hydrolysis. UniProt documents extensive mutagenesis
      data affecting ATPase activity (e.g., A41V causes 98% reduction, G83D abolishes activity).
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HSP82 functions as a homodimer and forms complexes with many co-chaperones and client proteins.
    action: ACCEPT
    reason: >-
      HSP82 is a homodimer and forms well-characterized complexes with co-chaperones (STI1, AHA1, SBA1, CDC37,
      CPR6, CPR7, CNS1, SSE1). Crystal structure of HSP82-SBA1-ATP closed complex (PDB:2CG9, PMID:16625188)
      confirms complex formation. ComplexPortal entry CPX-1276 (HMC complex) is documented.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      IBA annotation for plasma membrane localization of HSP82. While Hsp90 is primarily cytoplasmic,
      some evidence exists for plasma membrane association in other organisms.
    action: KEEP_AS_NON_CORE
    reason: >-
      HSP82 is primarily cytoplasmic (IDA PMID:32920053, PMID:27385335). Plasma membrane localization
      is not well-established for the yeast protein specifically, but the IBA inference from orthologs
      is plausible for a minor pool. Not a core localization.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HSP82 binds ATP as part of its chaperone cycle. Well-established by crystallography.
    action: ACCEPT
    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.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HSP82 is a cytosolic protein. IBA annotation is correct.
    action: ACCEPT
    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.
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HSP82 stabilizes client proteins as part of its chaperone function. IBA annotation is appropriate.
    action: ACCEPT
    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."
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      HSP82 is the heat-inducible Hsp90 isoform, centrally involved in heat stress response.
    action: ACCEPT
    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.
- 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. HSP82 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. 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.
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      IBA annotation for perinuclear localization. HSP82 is primarily cytoplasmic with some nuclear
      presence; perinuclear enrichment is plausible from ortholog data.
    action: KEEP_AS_NON_CORE
    reason: >-
      HSP82 is found in both cytoplasm and nucleus (IDA PMID:32920053). Perinuclear localization
      is inferred from orthologs and may represent a minor pool. Not a primary localization.
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      IEA annotation from UniProt keyword mapping. Broader than ATP binding but not incorrect.
    action: ACCEPT
    reason: >-
      Nucleotide binding is a parent term of ATP binding. While more specific IBA and IEA annotations
      for ATP binding exist, this broader IEA annotation is not incorrect and reflects the UniProt
      keyword mapping. It is redundant with the more specific ATP binding annotation but acceptable.
- 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, mediated through its general chaperone role on client proteins in the R2TP
      pathway.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      IEA annotation for ATP binding from InterPro/ARBA. Consistent with IBA and experimental evidence.
    action: ACCEPT
    reason: >-
      Redundant with IBA annotation but correct. ATP binding is a core molecular function of HSP82.
- 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 multiple IDA and HDA evidence for cytoplasmic localization.
- 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.
- 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:12235160) annotations for ATPase activity.
- 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 IDA/IMP evidence.
    action: KEEP_AS_NON_CORE
    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.
- 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
- 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 HSP82.
    action: ACCEPT
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11805837
  review:
    summary: >-
      IPI from large-scale mass spectrometry 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. 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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12604615
  review:
    summary: >-
      IPI from study of Aha1 binding to Hsp90. Specific interaction with co-chaperone.
    action: MARK_AS_OVER_ANNOTATED
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14729968
  review:
    summary: >-
      IPI from ctf13/RSC study. Generic 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:15102838
  review:
    summary: >-
      IPI from Hap1 interaction study. HSP82 interacts with the transcription factor Hap1.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      While HSP82-Hap1 interaction is genuine, "protein binding" is uninformative 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). Many interactions detected.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Large-scale study detecting many chaperone-client and chaperone-cochaperone interactions. "Protein
      binding" is uninformative for a chaperone.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15879519
  review:
    summary: >-
      IPI from yeast two-hybrid screen for Hsp90 interactors.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone with extensive interaction network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16407978
  review:
    summary: >-
      IPI from Ppt1 phosphatase study. Ppt1 is a dedicated regulator of Hsp90.
    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:16625188
  review:
    summary: >-
      IPI from crystal structure of HSP82-SBA1-nucleotide complex.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      While the SBA1 interaction is structurally characterized, "protein binding" is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18268103
  review:
    summary: >-
      IPI from R2TP complex/snoRNP assembly 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: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:18818696
  review:
    summary: >-
      IPI from Sgt1 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:18833289
  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:19536198
  review:
    summary: >-
      IPI from atlas of chaperone-protein interactions.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone. This study itself maps the chaperone interaction network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21170051
  review:
    summary: >-
      IPI from mixed Hsp90-cochaperone 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: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:21892170
  review:
    summary: >-
      IPI from structural analysis of Hsp90-p53 interaction.
    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:23396352
  review:
    summary: >-
      IPI from Aha1 integration into Hsp90 co-chaperone cycle 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:24012479
  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:24794838
  review:
    summary: >-
      IPI from Tel2-Hsp90-Pih1 structural 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.
    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:9817749
  review:
    summary: >-
      IPI from study showing Hsp90 function depends on ATP binding and hydrolysis.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone. The actual finding is about
      ATP-dependent chaperone function, not generic protein binding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9819422
  review:
    summary: >-
      IPI from Cns1/CPR7 interaction study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative "protein binding" for a chaperone.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:16625188
  review:
    summary: >-
      HSP82 forms homodimers as part of its functional cycle. The crystal structure (PDB:2CG9)
      confirms dimerization.
    action: ACCEPT
    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.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:18268103
  review:
    summary: >-
      Additional evidence for HSP82 homodimerization.
    action: ACCEPT
    reason: >-
      Consistent with known Hsp90 dimerization. Duplicate annotation with different reference is fine.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:19696785
  review:
    summary: >-
      HSP82 homodimerization via C-terminal domain switch point study.
    action: ACCEPT
    reason: >-
      C-terminal domain dimerization dynamics are important for the conformational cycle.
      Mutagenesis of A577 modulates dimerization, ATPase, and client activation.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:20736353
  review:
    summary: >-
      HSP82 C-terminal dimerization dynamics study.
    action: ACCEPT
    reason: >-
      Further confirmation of homodimerization as essential for the conformational cycle.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:23396352
  review:
    summary: >-
      HSP82 homodimerization in context of Aha1 co-chaperone cycle.
    action: ACCEPT
    reason: >-
      Consistent with known Hsp90 dimerization.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:24794838
  review:
    summary: >-
      HSP82 homodimerization in Tel2-Hsp90-Pih1 study.
    action: ACCEPT
    reason: >-
      Consistent with known Hsp90 dimerization.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:31454312
  review:
    summary: >-
      HSP82 homodimerization in paralog heteromer study.
    action: ACCEPT
    reason: >-
      Consistent with known Hsp90 dimerization and also documents HSP82-HSC82 heterodimerization.
- term:
    id: GO:0070482
    label: response to oxygen levels
  evidence_type: NAS
  original_reference_id: PMID:9632766
  review:
    summary: >-
      NAS annotation from ComplexPortal, based on HSP82 involvement in HAP1-mediated heme signaling.
    action: KEEP_AS_NON_CORE
    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).
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:32920053
  review:
    summary: >-
      IDA evidence for nuclear localization from starvation phosphorylation study.
    action: KEEP_AS_NON_CORE
    reason: >-
      HSP82 is primarily cytoplasmic but a nuclear pool exists, possibly enhanced during starvation.
      The study showed phosphorylation-dependent nuclear localization during starvation in S. cerevisiae.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:32920053
  review:
    summary: >-
      IDA evidence for cytoplasmic localization.
    action: ACCEPT
    reason: >-
      Core localization of HSP82. Consistent with multiple lines of evidence.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IDA
  original_reference_id: PMID:12235160
  review:
    summary: >-
      Direct assay evidence for ATPase activity of HSP82.
    action: ACCEPT
    reason: >-
      Core molecular function. Direct biochemical measurement of ATPase activity.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IMP
  original_reference_id: PMID:27068472
  review:
    summary: >-
      Mutant phenotype evidence for ATPase activity from systematic mutant analysis.
    action: ACCEPT
    reason: >-
      Systematic mutant analysis showing ATPase activity is required for client-specific
      and general Hsp90 functions. Complements IDA evidence.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: HDA
  original_reference_id: PMID:11914276
  review:
    summary: >-
      High-throughput data for cytoplasmic localization.
    action: ACCEPT
    reason: >-
      Consistent with IDA evidence.
- 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. Consistent with IDA evidence.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:27385335
  review:
    summary: >-
      IDA from split-GFP system at septin collar.
    action: ACCEPT
    reason: >-
      Consistent with cytoplasmic localization.
- term:
    id: GO:0051604
    label: protein maturation
  evidence_type: IMP
  original_reference_id: PMID:27068472
  review:
    summary: >-
      IMP evidence from systematic mutant analysis showing HSP82 is required for protein maturation.
    action: ACCEPT
    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.
- 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.
      This is a legitimate client-dependent function but not a core function of HSP82.
- term:
    id: GO:0006458
    label: "'de novo' protein folding"
  evidence_type: IDA
  original_reference_id: PMID:10564510
  review:
    summary: >-
      Direct assay evidence for de novo protein folding by HSP82.
    action: ACCEPT
    reason: >-
      Study of N- and C-terminal domain contributions to Hsp90 function in S. cerevisiae.
      Demonstrates involvement in de novo protein folding.
- term:
    id: GO:0006458
    label: "'de novo' protein folding"
  evidence_type: IMP
  original_reference_id: PMID:9371781
  review:
    summary: >-
      IMP evidence for de novo protein folding from in vivo function study.
    action: ACCEPT
    reason: >-
      Study of in vivo functions of Hsp90 in S. cerevisiae. Demonstrates role in de novo protein
      folding through mutant analysis.
- term:
    id: GO:0006970
    label: response to osmotic stress
  evidence_type: IMP
  original_reference_id: PMID:16487343
  review:
    summary: >-
      IMP evidence showing Hsp90 is required for high osmotic stress response.
    action: KEEP_AS_NON_CORE
    reason: >-
      Hsp90 is required for the osmotic stress response, likely through chaperoning stress-responsive
      kinases (e.g., Hog1 pathway clients). This is a stress-responsive function but secondary to the
      core chaperone activity.
- term:
    id: GO:0032212
    label: positive regulation of telomere maintenance via telomerase
  evidence_type: IDA
  original_reference_id: PMID:17954556
  review:
    summary: >-
      IDA evidence for positive regulation of telomere maintenance via telomerase.
    action: KEEP_AS_NON_CORE
    reason: >-
      Hsp90 modulates multiple telomerase activities. This is a client-dependent function where
      Hsp90 chaperones telomerase components. Not a core function of HSP82 itself.
- term:
    id: GO:0032212
    label: positive regulation of telomere maintenance via telomerase
  evidence_type: IMP
  original_reference_id: PMID:17954556
  review:
    summary: >-
      IMP evidence for telomerase regulation.
    action: KEEP_AS_NON_CORE
    reason: >-
      Complements IDA evidence. Client-dependent function.
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IMP
  original_reference_id: PMID:9371781
  review:
    summary: >-
      IMP evidence for protein refolding activity from in vivo function study.
    action: ACCEPT
    reason: >-
      Protein refolding is a core function of Hsp90. The in vivo study demonstrates this capacity.
- term:
    id: GO:0043248
    label: proteasome assembly
  evidence_type: IDA
  original_reference_id: PMID:12853471
  review:
    summary: >-
      IDA evidence for proteasome assembly involvement.
    action: KEEP_AS_NON_CORE
    reason: >-
      HSP82 assists in proteasome assembly as a client-dependent function. The chaperone assists
      proteasome maturation but this is secondary to its core function.
- term:
    id: GO:0043248
    label: proteasome assembly
  evidence_type: IMP
  original_reference_id: PMID:12853471
  review:
    summary: >-
      IMP evidence for proteasome assembly.
    action: KEEP_AS_NON_CORE
    reason: >-
      Complements IDA evidence. Client-dependent function.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:10564510
  review:
    summary: >-
      IDA evidence showing HSP82 binds unfolded/denatured proteins. Term proposed for obsoletion.
    action: MODIFY
    reason: >-
      While the experimental evidence is solid (HSP82 does bind unfolded proteins as shown by
      PMID:10564510), 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
- term:
    id: GO:0032204
    label: regulation of telomere maintenance
  evidence_type: IMP
  original_reference_id: PMID:21829731
  review:
    summary: >-
      IMP evidence from CACAO annotation showing HSP90 controls SIR2-mediated gene silencing
      and telomere maintenance.
    action: KEEP_AS_NON_CORE
    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.
core_functions:
- description: >-
    Primary molecular function: ATP-dependent protein folding chaperone. HSP82 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:12235160), unfolded
    protein binding (PMID:10564510), and de novo protein folding (PMID:10564510). Crystal
    structures confirm ATP-dependent conformational cycle (PDB:2CG9).
  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
- description: >-
    ATPase activity is fundamental to the Hsp90 chaperone cycle. Directly demonstrated by
    IDA (PMID:12235160) and IMP (PMID:27068472). Extensive mutagenesis data documents residues
    critical for ATPase activity.
  molecular_function:
    id: GO:0016887
    label: ATP hydrolysis activity
  directly_involved_in:
  - id: GO:0006457
    label: protein folding
  locations:
  - id: GO:0005737
    label: cytoplasm
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- 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: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10564510
  title: Contribution of N- and C-terminal domains to the function of Hsp90 in Saccharomyces
    cerevisiae.
  findings:
  - statement: Direct evidence for de novo protein folding and unfolded protein binding by HSP82
- id: PMID:11805837
  title: Systematic identification of protein complexes in Saccharomyces cerevisiae
    by mass spectrometry.
  findings: []
- id: PMID:11914276
  title: Subcellular localization of the yeast proteome.
  findings: []
- id: PMID:12235160
  title: N-terminal residues regulate the catalytic efficiency of the Hsp90 ATPase cycle.
  findings:
  - statement: Direct biochemical assay of ATPase activity
- id: PMID:12604615
  title: Aha1 binds to the middle domain of Hsp90, contributes to client protein activation,
    and stimulates the ATPase activity of the molecular chaperone.
  findings: []
- id: PMID:12853471
  title: The molecular chaperone Hsp90 plays a role in the assembly and maintenance of the 26S proteasome.
  findings: []
- id: PMID:14562095
  title: Global analysis of protein localization in budding yeast.
  findings: []
- id: PMID:14729968
  title: The ctf13-30/CTF13 genomic haploinsufficiency modifier screen identifies
    the yeast chromatin remodeling complex RSC, which is required for the establishment
    of sister chromatid cohesion.
  findings: []
- id: PMID:15102838
  title: 'A novel mode of chaperone action: heme activation of Hap1 by enhanced association
    of Hsp90 with the repressed Hsp70-Hap1 complex.'
  findings: []
- id: PMID:15766533
  title: 'Navigating the chaperone network: an integrative map of physical and genetic
    interactions mediated by the hsp90 chaperone.'
  findings: []
- id: PMID:15879519
  title: A two-hybrid screen of the yeast proteome for Hsp90 interactors
  findings: []
- id: PMID:16407978
  title: The phosphatase Ppt1 is a dedicated regulator of the molecular chaperone
    Hsp90.
  findings: []
- id: PMID:16429126
  title: Proteome survey reveals modularity of the yeast cell machinery.
  findings: []
- id: PMID:16487343
  title: The molecular chaperone Hsp90 is required for high osmotic stress response
    in Saccharomyces cerevisiae.
  findings: []
- id: PMID:16554755
  title: Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
  findings: []
- id: PMID:16625188
  title: Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex.
  findings:
  - statement: Crystal structure of full-length Hsp82 dimer in closed conformation with SBA1 and ATP
- id: PMID:17954556
  title: The hsp90 molecular chaperone modulates multiple telomerase activities.
  findings: []
- id: PMID:18268103
  title: Molecular chaperone Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex
    activity that regulates snoRNA accumulation.
  findings: []
- id: PMID:18719252
  title: High-quality binary protein interaction map of the yeast interactome network.
  findings: []
- id: PMID:18818696
  title: Structural and functional coupling of Hsp90- and Sgt1-centred multi-protein
    complexes.
  findings: []
- id: PMID:18833289
  title: Structural and functional analysis of SGT1-HSP90 core complex required for innate immunity in plants.
  findings: []
- id: PMID:19536198
  title: 'An atlas of chaperone-protein interactions in Saccharomyces cerevisiae:
    implications to protein folding pathways in the cell.'
  findings: []
- id: PMID:19696785
  title: Hsp90 is regulated by a switch point in the C-terminal domain.
  findings: []
- id: PMID:20736353
  title: Dynamics of heat shock protein 90 C-terminal dimerization is an important
    part of its conformational cycle.
  findings: []
- id: PMID:21170051
  title: Mixed Hsp90-cochaperone complexes are important for the progression of the
    reaction cycle.
  findings: []
- id: PMID:21734642
  title: Combinatorial depletion analysis to assemble the network architecture of
    the SAGA and ADA chromatin remodeling complexes.
  findings: []
- id: PMID:21829731
  title: HSP90 controls SIR2 mediated gene silencing.
  findings: []
- id: PMID:21892170
  title: Structural analysis of the interaction between Hsp90 and the tumor suppressor
    protein p53.
  findings: []
- id: PMID:23217712
  title: CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle
    progression.
  findings: []
- id: PMID:23396352
  title: Integration of the accelerator Aha1 in the Hsp90 co-chaperone cycle.
  findings: []
- id: PMID:24012479
  title: High-resolution structural analysis shows how Tah1 tethers Hsp90 to the R2TP complex.
  findings: []
- id: PMID:24794838
  title: Structural basis for phosphorylation-dependent recruitment of Tel2 to Hsp90
    by Pih1.
  findings: []
- id: PMID:27068472
  title: Systematic Mutant Analyses Elucidate General and Client-Specific Aspects
    of Hsp90 Function.
  findings:
  - statement: Systematic mutant analysis of Hsp90 function
- id: PMID:27385335
  title: Detection of protein-protein interactions at the septin collar in Saccharomyces
    cerevisiae using a tripartite split-GFP system.
  findings: []
- id: PMID:31454312
  title: The role of structural pleiotropy and regulatory evolution in the retention
    of heteromers of paralogs.
  findings: []
- id: PMID:32920053
  title: A Single Site Phosphorylation on Hsp82 Ensures Cell Survival during Starvation
    in Saccharomyces cerevisiae.
  findings: []
- id: PMID:37968396
  title: The social and structural architecture of the yeast protein interactome.
  findings: []
- id: PMID:9371781
  title: In vivo functions of the Saccharomyces cerevisiae Hsp90 chaperone.
  findings:
  - statement: In vivo demonstration of protein folding and refolding functions
- id: PMID:9632766
  title: 'Molecular mechanism governing heme signaling in yeast: a higher-order complex
    mediates heme regulation of the transcriptional activator HAP1.'
  findings: []
- id: PMID:9817749
  title: In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis.
  findings: []
- id: PMID:9819422
  title: Cns1 is an essential protein associated with the hsp90 chaperone complex
    in Saccharomyces cerevisiae that can restore cyclophilin 40-dependent functions
    in cpr7Delta cells.
  findings: []
- id: PMID:2674684
  title: hsp82 is an essential protein that is required in higher concentrations for
    growth of cells at higher temperatures.
  findings:
  - statement: HSP82 is essential and required at higher concentrations for growth at elevated temperatures