id: P02828
gene_symbol: Hsp83
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:7227
  label: Drosophila melanogaster
description: Hsp83 is the sole Drosophila melanogaster member of the HSP90 family
  of ATP-dependent molecular chaperones. It promotes the maturation, structural maintenance,
  and proper regulation of specific client proteins involved in cell cycle control,
  signal transduction, piRNA biogenesis, and centrosome function. Hsp83 undergoes
  a functional ATPase cycle that induces conformational changes in client proteins,
  thereby causing their activation. It interacts dynamically with various co-chaperones
  (Hop, Shu, Dpit47, Morgana) that modulate its substrate recognition, ATPase cycle,
  and chaperone function. In addition to its canonical chaperone role, Hsp83 has a
  non-chaperone membrane-deforming function mediated by an amphipathic helix that
  promotes exosome release. Hsp83 is constitutively expressed and further induced
  by heat stress; it is also expressed during oogenesis and plays roles in developmental
  processes including centrosome cycle, cell cycle exit, mRNA localization, and sleep
  regulation.
existing_annotations:
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Hsp83/HSP90 is a well-established molecular chaperone whose primary biological
      role is protein folding. The IBA annotation is supported by strong phylogenetic
      evidence across multiple orthologs (PMID:10716925, UniProt function annotation).
      UniProt states Hsp83 is a "Molecular chaperone that promotes the maturation,
      structural maintenance and proper regulation of specific target proteins."
    action: ACCEPT
    reason: Protein folding is the core biological process of HSP90 family chaperones.
      IBA is well-supported by orthologs and consistent with all functional literature
      on Hsp83.
    supported_by:
    - reference_id: PMID:10716925
      supporting_text: a member of the highly conserved Hsp90 family including chaperones
        known to maintain the activity of many proteins
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Hsp83/HSP90 has intrinsic ATPase activity that is essential for its chaperone
      cycle. The UniProt record notes it "Undergoes a functional cycle that is linked
      to its ATPase activity." The IBA annotation is supported by phylogenetic inference
      from multiple HSP90 orthologs with experimentally characterized ATPase activity.
    action: ACCEPT
    reason: ATP hydrolysis is a core enzymatic activity of the HSP90 family. The HATPase_c
      domain is well characterized structurally and the ATPase cycle drives the chaperone
      conformational changes. Consistent with IBA evidence across the HSP90 family.
    supported_by:
    - reference_id: PMID:29775584
      supporting_text: the Hsp90 system (Hop, Hsp90, and p23) together render Ago2
        into an open, active form
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: HSP90 family members function as homodimers and form multi-protein complexes
      with co-chaperones (Hop, p23, Cdc37, Aha1) and client proteins. UniProt states
      Hsp83 is a "Homodimer" and describes multiple complexes including with Hop/piwi,
      sicily/ND-42, Dpit47/Hsp70aa, and Nup358. The IBA annotation to the generic
      protein-containing complex is correct but very general.
    action: ACCEPT
    reason: HSP90 is known to form multiple protein complexes. While the term is generic,
      IBA annotations at this level are acceptable as they reflect the phylogenetic
      inference. More specific complex annotations (GO:0101031, GO:0034663) are captured
      elsewhere.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: IBA annotation to plasma membrane is supported by phylogenetic inference
      from multiple HSP90 orthologs. Hsp83 was also detected at the plasma membrane
      by HDA (PMID:19317464). Hsp90 has an amphipathic helix that allows membrane
      interaction (PMID:30193096), which could explain plasma membrane localization.
    action: ACCEPT
    reason: Plasma membrane localization is consistent with both the IBA evidence
      from orthologs and the independent HDA evidence from proteomics (PMID:19317464).
      The amphipathic helix-mediated membrane interaction described in PMID:30193096
      provides a mechanistic basis.
    supported_by:
    - reference_id: PMID:30193096
      supporting_text: Hsp90 also has the ability to directly interact with and deform
        membranes via an evolutionarily conserved amphipathic helix
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ATP binding is a fundamental property of HSP90 family members, mediated
      by the HATPase_c domain. UniProt lists multiple ATP binding residues (positions
      39, 81, 100, 126, 385) and the keyword "ATP-binding." IBA annotation is well
      supported.
    action: ACCEPT
    reason: ATP binding is intrinsic to the HSP90 ATPase domain. Structurally characterized
      across the family.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Cytosolic localization of HSP90 family members is well established. IBA
      annotation from multiple orthologs. Consistent with UniProt subcellular location
      annotation to "Cytoplasm" and multiple IDA/HDA annotations to cytoplasm in Drosophila.
    action: ACCEPT
    reason: Cytosol is the primary localization for cytoplasmic HSP90 family members.
      IBA is well supported.
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: HSP90 chaperones stabilize client proteins, preventing their degradation.
      UniProt states Hsp83 "promotes the maturation, structural maintenance and proper
      regulation of specific target proteins." IBA from multiple orthologs. Loss of
      Hsp90 function leads to decreased levels of client proteins such as ND42 and
      NDUFS3 (PMID:23509070), directly demonstrating protein stabilization.
    action: ACCEPT
    reason: Protein stabilization is a core function of HSP90 -- client proteins are
      destabilized and degraded when HSP90 is inhibited. Well supported by phylogenetic
      evidence and direct experimental data in Drosophila.
    supported_by:
    - reference_id: PMID:23509070
      supporting_text: Both NDUFS3 and ND42 are severely down-regulated in sicily
        mutants, whereas other mitochondrial proteins, including Porin (Graham et
        al., 2010) and cytochrome c, are unaltered or slightly increased
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Hsp83 is a heat shock protein that is upregulated in response to heat
      stress. IBA from multiple orthologs. Consistent with IEP evidence from PMID:16595740
      showing Hsp83 protein levels increase after heat shock. Name itself (Heat shock
      protein 83) reflects this function.
    action: ACCEPT
    reason: Cellular response to heat is a defining characteristic of heat shock proteins.
      IBA supported by expression and functional data in Drosophila.
    supported_by:
    - reference_id: PMID:16595740
      supporting_text: increases in the levels of Hsp83 and DnaJ-1 proteins but not
        in the inducible form of Hsp70 were detected by Western blot analysis
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: GO:0051082 "unfolded protein binding" is proposed for obsoletion. HSP90
      does not simply bind unfolded proteins like holdase chaperones; rather, it acts
      as an ATP-dependent foldase that binds near-native client proteins and assists
      their maturation through conformational change driven by ATP hydrolysis. The
      correct MF term is GO:0140662 "ATP-dependent protein folding chaperone."
    action: MODIFY
    reason: GO:0051082 is proposed for obsoletion and does not accurately describe
      the HSP90 mechanism. HSP90 does not primarily bind unfolded proteins; it binds
      near-native, partially folded client proteins and uses ATP hydrolysis to drive
      their maturation. The replacement term GO:0140662 "ATP-dependent protein folding
      chaperone" precisely captures the molecular function.
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
    supported_by:
    - reference_id: PMID:29775584
      supporting_text: the Hsp90 system is required to extend the dwell time of Ago2
        in the open state, which must be transiently primed by the Hsp70 system
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: IBA annotation to perinuclear region of cytoplasm is supported by phylogenetic
      inference from multiple orthologs. Also supported by direct experimental evidence
      in Drosophila (IDA, PMID:22902557) where Hsp83 was observed in perinuclear region
      via the piRNA pathway work with Shutdown (Shu).
    action: ACCEPT
    reason: Consistent with IBA evidence and directly confirmed by IDA in Drosophila
      (PMID:22902557).
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: IEA annotation from UniProtKB keyword mapping (KW-0547 "Nucleotide-binding").
      Hsp83 is indeed an ATP-binding protein with a well-characterized nucleotide
      binding pocket. This is a broader parent term of ATP binding (GO:0005524) which
      is already annotated with IBA evidence.
    action: ACCEPT
    reason: Correct but redundant with the more specific ATP binding annotation. IEA
      annotations at broader levels than IBA are acceptable.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: IEA annotation for ATP binding from combined automated methods (InterPro:IPR001404,
      InterPro:IPR019805, UniProtKB-KW:KW-0067). Correct and consistent with IBA annotation
      for the same term.
    action: ACCEPT
    reason: Redundant with IBA annotation for the same GO term. Both are correct.
      Hsp83 has a well-characterized HATPase domain.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: IEA annotation from UniProt subcellular location vocabulary mapping.
      UniProt annotates Hsp83 subcellular location as "Cytoplasm." Consistent with
      multiple IDA and HDA annotations for cytoplasm.
    action: ACCEPT
    reason: Correct. Cytoplasmic localization is well established by multiple independent
      lines of evidence.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: IEA annotation from InterPro domain mapping (IPR001404, IPR019805). Protein
      folding is the core biological process of HSP90 family. Consistent with IBA
      and other evidence.
    action: ACCEPT
    reason: Correct. Redundant with IBA annotation. InterPro correctly maps the HSP90
      domain to the protein folding process.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: IEA annotation from InterPro domain mapping (IPR001404). ATP hydrolysis
      is intrinsic to the HATPase domain of HSP90. Consistent with IBA.
    action: ACCEPT
    reason: Correct. Redundant with IBA annotation. InterPro correctly maps the HSP90
      HATPase domain to ATP hydrolysis activity.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: IEA annotation from InterPro domain mapping. GO:0051082 is proposed for
      obsoletion. HSP90 does not function as a holdase chaperone that binds unfolded
      proteins; it is an ATP-dependent foldase that acts on near-native client proteins.
    action: MODIFY
    reason: Same issue as the IBA annotation for this term. GO:0051082 is proposed
      for obsoletion and does not accurately represent the HSP90 mechanism. Should
      be replaced with GO:0140662 "ATP-dependent protein folding chaperone."
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
- term:
    id: GO:0101031
    label: protein folding chaperone complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: IEA annotation from ARBA machine learning model (ARBA:ARBA00026483).
      HSP90 forms multiple chaperone complexes. Consistent with IDA evidence from
      PMID:33176138 for the same term.
    action: ACCEPT
    reason: Correct. HSP90 is a core component of protein folding chaperone complexes.
      Consistent with direct experimental evidence in Drosophila.
- 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 domain mapping (IPR001404). GO:0140662 "ATP-dependent
      protein folding chaperone" is the correct molecular function term for HSP90,
      accurately capturing its ATP-dependent chaperone mechanism. This is the term
      that should replace GO:0051082 across all annotations.
    action: ACCEPT
    reason: This is the most accurate MF term for HSP90 function. HSP90 binds client
      proteins and assists their folding/maturation through ATP hydrolysis-driven
      conformational changes.
    supported_by:
    - reference_id: PMID:29775584
      supporting_text: the Hsp90 system is required to extend the dwell time of Ago2
        in the open state
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22579285
  review:
    summary: IPI annotation from IntAct based on physical interaction with Nelf-E
      (P92204). PMID:22579285 showed Hsp90 localizes to promoters and stabilizes the
      NELF complex to maintain RNA polymerase II pausing. While the interaction is
      real, "protein binding" is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: The interaction with Nelf-E is likely reflecting Hsp83's chaperone activity
      on NELF complex stabilization. "Protein binding" is too generic and uninformative.
      The chaperone function is better captured by GO:0140662, and the biological
      outcome (gene expression regulation) is a downstream effect of chaperone activity.
    supported_by:
    - reference_id: PMID:22579285
      supporting_text: Hsp90 maintains and optimizes RNA polymerase II pausing via
        stabilization of the negative elongation factor complex (NELF)
- term:
    id: GO:0034663
    label: endoplasmic reticulum chaperone complex
  evidence_type: IPI
  original_reference_id: PMID:22099462
  review:
    summary: IPI annotation based on physical interaction evidence (PMID:22099462),
      with interactors FB:FBgn0038749 and FB:FBgn0289994. PMID:22099462 identifies
      XPORT as a chaperone for TRP and rhodopsin that interacts with Hsp90 in the
      ER/secretory pathway. Hsp83 is primarily a cytoplasmic chaperone, and ER localization
      would be atypical for the cytoplasmic HSP90 (as opposed to ER-resident GRP94/Hsp90B1).
    action: UNDECIDED
    reason: PMID:22099462 shows XPORT interacts with Hsp90 in the ER context, but
      ER chaperone complex localization is unexpected for a cytoplasmic HSP90 family
      member. This could represent a transient interaction during client protein processing
      in the secretory pathway. Requires further investigation.
    supported_by:
    - reference_id: PMID:22099462
      supporting_text: XPORT is a resident ER and secretory pathway protein that interacts
        with TRP and Rh1, as well as with Hsp27 and Hsp90
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ISS annotation transferred from human HSP90AA1 (P07900). A minor pool
      of HSP90 has been reported in mitochondria in mammalian cells. Hsp83 interacts
      with Sicily for chaperoning ND42 before mitochondrial import (PMID:23509070),
      but this occurs in the cytoplasm. Mitochondrial localization of the fly protein
      itself is not directly demonstrated.
    action: KEEP_AS_NON_CORE
    reason: Mitochondrial localization is plausible based on mammalian ortholog data
      but not directly demonstrated in Drosophila. The cytoplasmic chaperoning of
      mitochondrial proteins (PMID:23509070) does not require Hsp83 itself to localize
      to mitochondria.
    supported_by:
    - reference_id: PMID:23509070
      supporting_text: Sicily preprotein interacts with cytosolic Hsp90 to chaperone
        the CI subunit, ND42, before mitochondrial import
- term:
    id: GO:0097753
    label: membrane bending
  evidence_type: IDA
  original_reference_id: PMID:30193096
  review:
    summary: IDA annotation based on direct demonstration in PMID:30193096 that Hsp90
      can directly interact with and deform membranes via an evolutionarily conserved
      amphipathic helix. This is a non-chaperone function structurally separated from
      the protein folding activity.
    action: KEEP_AS_NON_CORE
    reason: Membrane bending is a genuine, experimentally validated function of Hsp90
      mediated by its amphipathic helix. However, it is a non-canonical function distinct
      from the core chaperone activity and therefore non-core. The paper explicitly
      states they "structurally separated the Hsp90 membrane-deforming function from
      its well-characterized chaperone activity."
    supported_by:
    - reference_id: PMID:30193096
      supporting_text: Hsp90 also has the ability to directly interact with and deform
        membranes via an evolutionarily conserved amphipathic helix
    - reference_id: PMID:30193096
      supporting_text: we structurally separated the Hsp90 membrane-deforming function
        from its well-characterized chaperone activity
- term:
    id: GO:0098866
    label: multivesicular body fusion to apical plasma membrane
  evidence_type: IMP
  original_reference_id: PMID:30193096
  review:
    summary: IMP annotation from PMID:30193096. The amphipathic helix of Hsp90 promotes
      the fusion of multivesicular bodies (MVBs) with the plasma membrane, enabling
      exosome release. Mutations and drugs that stabilize the open Hsp90 dimer expose
      the helix and allow MVB fusion.
    action: KEEP_AS_NON_CORE
    reason: This is a genuine but non-core function mediated by the non-chaperone
      membrane-deforming activity of Hsp90. Not a typical chaperone function.
    supported_by:
    - reference_id: PMID:30193096
      supporting_text: this amphipathic helix allows exosome release by promoting
        the fusion of multivesicular bodies (MVBs) with the plasma membrane
- term:
    id: GO:0070922
    label: RISC complex assembly
  evidence_type: IGI
  original_reference_id: PMID:29775584
  review:
    summary: IGI annotation from PMID:29775584 with genetic interactors FB:FBgn0037728
      and FB:FBgn0266599. The paper demonstrates that Hsp70/Hsp90 chaperone machinery
      is required for loading small RNAs into Argonaute, a key step in RISC assembly.
      The Hsp90 system captures and stabilizes the open, active form of Ago2.
    action: ACCEPT
    reason: RISC complex assembly is a well-characterized function of the Hsp90 chaperone
      system. Hsp90 is required for conformational activation of Argonaute to enable
      small RNA loading. This is a specific manifestation of its core chaperone function
      on a defined client protein complex.
    supported_by:
    - reference_id: PMID:29775584
      supporting_text: Loading of small RNAs into Argonaute, the core protein in RNA
        silencing, requires the Hsp70/Hsp90 chaperone machinery
    - reference_id: PMID:29775584
      supporting_text: the Hsp90 system is required to extend the dwell time of Ago2
        in the open state
- term:
    id: GO:0070922
    label: RISC complex assembly
  evidence_type: IPI
  original_reference_id: PMID:33176138
  review:
    summary: IPI annotation from PMID:33176138 with interactors FB:FBgn0036020, FB:FBgn0087035,
      and FB:FBgn0262739. PMID:33176138 identifies Cyclophilin 40 as a testis-specialized
      Hsp90 co-chaperone that modulates Ago2-RISC formation. Cyp40 interacts with
      Ago2 through Hsp90 and promotes the build-up of Ago2-bound miRNAs.
    action: ACCEPT
    reason: Consistent with the IGI evidence from PMID:29775584 and with the known
      role of HSP90 in Argonaute maturation and RISC assembly. Additional IPI evidence
      strengthens the annotation.
    supported_by:
    - reference_id: PMID:33176138
      supporting_text: Cyp40 interacts with duplex-incorporating Ago2 through Hsp90
        in vitro and selectively promotes the build-up of Ago2-bound miRNAs
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31907206
  review:
    summary: IPI annotation from UniProt based on interaction with Morgana/CHORD (Q9VCC0).
      PMID:31907206 showed that Morgana co-purifies with the Hsp90-R2TP-TTT supercomplex.
      This is a typical co-chaperone interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: '"Protein binding" is uninformative. The interaction with Morgana reflects
      Hsp83''s role as part of the Hsp90-R2TP-TTT chaperone supercomplex. This is
      better captured by the chaperone complex annotations (GO:0101031) and the ATP-dependent
      protein folding chaperone MF term (GO:0140662).'
    supported_by:
    - reference_id: PMID:31907206
      supporting_text: Mora localises to mitotic spindles and co-purifies with the
        Hsp90-R2TP-TTT supercomplex and with additional well-known Hsp90 co-chaperones
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ISS annotation transferred from human HSP90AA1 (P07900). ATP hydrolysis
      is well established for HSP90 family members. Consistent with IBA evidence for
      the same term.
    action: ACCEPT
    reason: Correct. Redundant with IBA. ATP hydrolysis is a core function of the
      HSP90 family.
- term:
    id: GO:0101031
    label: protein folding chaperone complex
  evidence_type: IDA
  original_reference_id: PMID:33176138
  review:
    summary: IDA annotation from PMID:33176138 directly demonstrating Hsp83 as part
      of a protein folding chaperone complex. PMID:33176138 shows Hsp90 machinery
      acts as chaperone complex for Ago2 loading during RISC assembly. HSP90 forms
      complexes with co-chaperones (Hop, p23, Cdc37, Cyp40, etc.) to constitute chaperone
      machinery.
    action: ACCEPT
    reason: HSP90 is a core component of chaperone complexes. IDA evidence directly
      confirms this in Drosophila. Consistent with UniProt subunit annotations describing
      multiple Hsp83-containing complexes.
    supported_by:
    - reference_id: PMID:33176138
      supporting_text: In gene silencing, Hsp90 chaperone machinery assists Argonaute
        (Ago) binding and unwinding of silencing small RNA (sRNA) duplexes
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23509070
  review:
    summary: IPI annotation from UniProt based on interaction with Sicily (P91929)
      and ND-42/NDUFA10 (Q9VYS5). PMID:23509070 showed Sicily is a cytosolic chaperone
      for a mitochondrial Complex I subunit, and Hsp83 forms a complex with Sicily
      and ND42. Hsp90 binds to Sicily directly and coimmunoprecipitates ND42 only
      when Sicily is coexpressed.
    action: MARK_AS_OVER_ANNOTATED
    reason: '"Protein binding" is uninformative. The interaction with Sicily reflects
      Hsp83''s chaperone function in chaperoning ND42 before mitochondrial import.
      Better captured by the ATP-dependent protein folding chaperone MF term (GO:0140662)
      and the protein stabilization BP term (GO:0050821).'
    supported_by:
    - reference_id: PMID:23509070
      supporting_text: Hsp90 binds to Sicily in an in vitro co-IP assay
- term:
    id: GO:0002052
    label: positive regulation of neuroblast proliferation
  evidence_type: IMP
  original_reference_id: PMID:30245208
  review:
    summary: IMP annotation from PMID:30245208. Hsp83 is both necessary and sufficient
      for neural stem cell reactivation by promoting the activation of InR pathway
      in larval brains. This is a downstream pleiotropic effect of Hsp83 chaperone
      function on signaling clients.
    action: KEEP_AS_NON_CORE
    reason: This is a downstream developmental phenotype of Hsp83 function, likely
      mediated through its role in insulin receptor signaling (same paper provides
      insulin receptor binding annotation). Non-core pleiotropic effect.
    supported_by:
    - reference_id: PMID:30245208
      supporting_text: Hsp83 is both necessary and sufficient for NSC reactivation
        by promoting the activation of InR pathway in larval brains in the presence
        of dietary amino acids
- term:
    id: GO:0005158
    label: insulin receptor binding
  evidence_type: IDA
  original_reference_id: PMID:30245208
  review:
    summary: IDA annotation from PMID:30245208 demonstrating direct binding of Hsp83
      to the insulin receptor. Both Hsp83 and its co-chaperone Cdc37 physically associate
      with InR. HSP90 is known to chaperone receptor tyrosine kinases in other systems.
      This likely reflects HSP90's general role in chaperoning kinase clients.
    action: KEEP_AS_NON_CORE
    reason: Insulin receptor binding is consistent with HSP90's well-known role as
      a kinase chaperone, but it represents a specific client interaction rather than
      a core molecular function. The core function is the ATP-dependent protein folding
      chaperone activity.
    supported_by:
    - reference_id: PMID:30245208
      supporting_text: Both Hsp83 and its co-chaperone Cdc37 physically associate
        with InR
- term:
    id: GO:0046628
    label: positive regulation of insulin receptor signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:30245208
  review:
    summary: IGI annotation from PMID:30245208 with genetic interactor FB:FBgn0283499.
      Hsp83 positively regulates insulin receptor signaling, consistent with its role
      in chaperoning the insulin receptor.
    action: KEEP_AS_NON_CORE
    reason: Downstream pleiotropic effect of Hsp83 chaperone function on insulin signaling.
      Non-core but experimentally supported.
    supported_by:
    - reference_id: PMID:30245208
      supporting_text: Hsp83 is both necessary and sufficient for NSC reactivation
        by promoting the activation of InR pathway in larval brains in the presence
        of dietary amino acids
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: HDA
  original_reference_id: PMID:26896675
  review:
    summary: HDA annotation from a genome-wide protein localization study (PMID:26896675)
      using GFP-tagged fosmid transgenes in Drosophila. Cytoplasmic localization is
      consistent with all other evidence.
    action: ACCEPT
    reason: Cytoplasm is the primary localization for Hsp83. Confirmed by multiple
      independent methods.
    supported_by:
    - reference_id: PMID:26896675
      supporting_text: A genome-wide resource for the analysis of protein localisation
        in Drosophila
- term:
    id: GO:0030911
    label: TPR domain binding
  evidence_type: IPI
  original_reference_id: PMID:27979731
  review:
    summary: 'IPI annotation from PMID:27979731 based on interaction of Hsp83 with
      the TPR domain of Nup358. The C-terminal MEEVD motif of HSP90 is a well-characterized
      TPR repeat-binding motif (UniProt: "The TPR repeat-binding motif mediates interaction
      with TPR repeat-containing proteins"). The interaction with Nup358 TPR domain
      facilitates nuclear import of Met, the juvenile hormone receptor.'
    action: ACCEPT
    reason: TPR domain binding is a core molecular function of HSP90 family members,
      mediated by the conserved C-terminal MEEVD motif. This is how HSP90 interacts
      with many co-chaperones (Hop, CHIP, Tom70, etc.) and other TPR-containing proteins.
    supported_by:
    - reference_id: PMID:27979731
      supporting_text: a tetratricopeptide repeat (TPR) domain at the N-terminal end
        of Nup358 interacts with Hsp83 and is indispensable for Met nuclear localization
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ISS annotation transferred from yeast HSP82 (P15108). Protein folding
      is well established for HSP90 family. Consistent with IBA and IEA evidence.
    action: ACCEPT
    reason: Correct. Redundant with IBA and IEA. Protein folding is the core biological
      process.
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ISS annotation transferred from yeast HSP82 (P15108). Cellular response
      to heat is well established for heat shock proteins. Consistent with IBA evidence.
    action: ACCEPT
    reason: Correct. Redundant with IBA. Heat shock response is a defining feature
      of HSP90 family.
- term:
    id: GO:0043248
    label: proteasome assembly
  evidence_type: IDA
  original_reference_id: PMID:15946124
  review:
    summary: IDA annotation from PMID:15946124. Hsp82 (Hsp83) was identified by mass
      spectrometry as the main Rpn10/p54-interacting protein after Zn2+-induced proteasome
      disassembly, suggesting a role in reassembly of the 26S proteasome.
    action: KEEP_AS_NON_CORE
    reason: The evidence shows Hsp83 interacts with Rpn10 after proteasome disassembly,
      suggesting a role in reassembly. This is consistent with HSP90's general chaperone
      function applied to proteasome components, but represents a specific client
      relationship rather than a core function.
    supported_by:
    - reference_id: PMID:15946124
      supporting_text: Hsp82 (heat-shock protein 82) has been identified by MS as
        the main Rpn10/p54-interacting protein, suggesting its role in the reassembly
        of the 26 S proteasome after Zn2+ removal
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: HDA
  original_reference_id: PMID:24292889
  review:
    summary: HDA annotation from PMID:24292889 (Ube3a proteasomal shuttle Rpn10 study).
      Cytoplasmic localization detected as part of a high-throughput study. Consistent
      with other evidence.
    action: ACCEPT
    reason: Cytoplasm localization is well established. Additional HDA evidence.
    supported_by:
    - reference_id: PMID:24292889
      supporting_text: Overexpression of these proteins leads to an enhanced accumulation
        of ubiquitinated proteins, further supporting the biochemical evidence of interaction
        obtained in neuronal cells
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: HDA
  original_reference_id: PMID:19317464
  review:
    summary: HDA annotation from PMID:19317464 (LOPIT subcellular proteomics study
      in Drosophila embryos). Plasma membrane localization detected in this systematic
      study. Consistent with IBA annotation and the amphipathic helix-mediated membrane
      interaction (PMID:30193096).
    action: ACCEPT
    reason: Plasma membrane localization supported by independent proteomics evidence
      and consistent with IBA and the membrane-deforming function.
    supported_by:
    - reference_id: PMID:19317464
      supporting_text: we apply LOPIT, a mass-spectrometry based technique that simultaneously
        maps proteins to specific subcellular compartments, to Drosophila embryos
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:18344983
  review:
    summary: IDA annotation from PMID:18344983. This paper is primarily about NMNAT
      as a chaperone, not about Hsp83 directly. The paper shows that NMNAT "displays
      chaperone function both in biochemical assays and cultured cells" and compares
      it to Hsp70. Hsp83 is mentioned as a control or comparison. Regardless, GO:0051082
      is proposed for obsoletion and the term does not correctly describe HSP90 function.
      HSP90 is an ATP-dependent foldase, not a holdase.
    action: MODIFY
    reason: GO:0051082 is proposed for obsoletion. The evidence in PMID:18344983 is
      primarily about NMNAT chaperone function, with Hsp83 as a comparison. The correct
      term for Hsp83 molecular function is GO:0140662 "ATP-dependent protein folding
      chaperone."
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
    supported_by:
    - reference_id: PMID:18344983
      supporting_text: NMNAT displays chaperone function both in biochemical assays
        and cultured cells, and it shares significant structural similarity with known
        chaperones
- term:
    id: GO:0008285
    label: negative regulation of cell population proliferation
  evidence_type: IMP
  original_reference_id: PMID:24086162
  review:
    summary: IMP annotation from PMID:24086162. Hsp83 mutation results in increased
      E2F-dependent transcription and ectopic cell proliferation in pupal tissues,
      demonstrating that Hsp83 is required for proper cell cycle exit. The paper proposes
      Cdh1/Fzr (APC/C activating subunit) is a client of Hsp83. Thus Hsp83 indirectly
      promotes cell cycle exit by chaperoning APC/C components.
    action: KEEP_AS_NON_CORE
    reason: This is a downstream phenotypic consequence of Hsp83 chaperone function
      on cell cycle regulators (APC/C components). The paper proposes "Cdh1/Fzr is
      a client protein of Hsp83." This is a pleiotropic effect of the core chaperone
      function, not a core function itself.
    supported_by:
    - reference_id: PMID:24086162
      supporting_text: Mutation of Hsp83, the Drosophila homolog of mammalian Hsp90,
        results in increased E2F-dependent transcription and ectopic cell proliferation
        in pupal tissues at a time when neighboring wild-type cells are postmitotic
    - reference_id: PMID:24086162
      supporting_text: we propose that Cdh1/Fzr is a client protein of Hsp83
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:22902557
  review:
    summary: IDA annotation from PMID:22902557. This paper studies the cochaperone
      Shutdown and piRNA biogenesis. Using a genomic GFP-tagged Hsp83 construct, the
      authors show that Hsp83 is enriched in a peri-nuclear rim in wild-type nurse
      cells, potentially reflecting nuage accumulation. Hsp83 colocalizes with unloaded
      AGO3 in cytoplasmic foci when piRNA biogenesis is disrupted.
    action: ACCEPT
    reason: Perinuclear region localization is directly demonstrated by IDA using
      GFP-tagged Hsp83 and is consistent with IBA evidence and the known role of Hsp83
      in piRNA biogenesis in germline nuage.
    supported_by:
    - reference_id: PMID:22902557
      supporting_text: Hsp83 was enriched in a peri-nuclear rim, potentially reflecting
        nuage accumulation
- term:
    id: GO:0005705
    label: polytene chromosome interband
  evidence_type: IDA
  original_reference_id: PMID:19144915
  review:
    summary: IDA annotation from PMID:19144915. This paper shows a direct molecular
      interaction between Hsp90 and Trithorax, and that Hsp90 cooperates with Trx
      at chromatin for maintaining the active expression state of targets like Hox
      genes. Polytene chromosome interband localization is consistent with the chromatin-binding
      function of Hsp90.
    action: ACCEPT
    reason: PMID:19144915 demonstrates Hsp90 interacts with Trithorax at chromatin
      to maintain active gene expression. Polytene chromosome interband localization
      is consistent with this chromatin-associated function and with the finding from
      PMID:22579285 that Hsp90 localizes to promoters.
    supported_by:
    - reference_id: PMID:19144915
      supporting_text: Hsp90 cooperates with Trx at chromatin for maintaining the
        active expression state of targets like the Hox genes
    additional_reference_ids:
    - PMID:22579285
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:19144915
  review:
    summary: IDA annotation from PMID:19144915. Cytoplasmic localization is consistent
      with all other evidence.
    action: ACCEPT
    reason: Cytoplasm localization is independently confirmed by many other studies.
      This annotation is redundant but correct.
    supported_by:
    - reference_id: PMID:19144915
      supporting_text: Molecular chaperone heat-shock protein 90 kDa (Hsp90) is known
        to facilitate the conformational maturation of a diverse range of proteins
        involved in different signal transduction pathways during development
- term:
    id: GO:0009631
    label: cold acclimation
  evidence_type: IEP
  original_reference_id: PMID:16313561
  review:
    summary: IEP annotation from PMID:16313561. Microarray analysis showed Hsp83 transcript
      was differentially expressed after cold hardening treatment (0 C for 2 h followed
      by recovery). The evidence is expression-based only (IEP), and does not demonstrate
      a direct functional role.
    action: KEEP_AS_NON_CORE
    reason: Based solely on expression evidence (IEP). Transcript upregulation during
      cold hardening does not prove a direct role in cold acclimation. However, Hsp83
      may contribute to protein homeostasis under cold stress. Keeping as non-core
      due to indirect evidence.
    supported_by:
    - reference_id: PMID:16313561
      supporting_text: stress proteins, including Hsp23, Hsp26, Hsp83 and Frost as
        well as membrane-associated proteins may contribute to the cold hardening
        response
- term:
    id: GO:0009408
    label: response to heat
  evidence_type: IEP
  original_reference_id: PMID:16595740
  review:
    summary: IEP annotation from PMID:16595740. Hsp83 protein levels were shown to
      increase after heat shock by Western blot analysis, even in a heat shock factor
      mutant (hsf4). As a constitutively expressed heat shock protein, Hsp83 upregulation
      during heat stress provides thermoprotection at synapses.
    action: ACCEPT
    reason: While IEP is weaker evidence, the response to heat is fundamental to heat
      shock proteins. The name "Heat shock protein 83" itself reflects this. The more
      specific term "cellular response to heat" (GO:0034605) is also annotated with
      IBA and ISS evidence.
    supported_by:
    - reference_id: PMID:16595740
      supporting_text: the compensatory upregulation of constitutively expressed Hsps,
        in the absence of the synthesis of the major inducible Hsp, Hsp70, could still
        provide substantial thermoprotection
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:19101615
  review:
    summary: IDA annotation from PMID:19101615. Hsp90 and Cup co-localize in the cytoplasm
      of developing germ-line cells within the germarium.
    action: ACCEPT
    reason: Cytoplasmic localization directly demonstrated during oogenesis. Consistent
      with all other cytoplasm annotations.
    supported_by:
    - reference_id: PMID:19101615
      supporting_text: Hsp90 and Cup co-localize in the cytoplasm of the developing
        germ-line cells within the germarium
- term:
    id: GO:0048477
    label: oogenesis
  evidence_type: IGI
  original_reference_id: PMID:19101615
  review:
    summary: IGI annotation from PMID:19101615 with genetic interactor Cup (FB:FBgn0000392).
      Lowering Hsp90 activity enhances oogenesis alterations linked to diverse cup
      mutant alleles, demonstrating a genetic interaction in oogenesis. Hsp90 is a
      component of the cap-binding complex and interacts with the translational repressor
      Cup during oogenesis.
    action: KEEP_AS_NON_CORE
    reason: Oogenesis involvement is a pleiotropic consequence of Hsp83 chaperone
      function during development. The paper shows Hsp90 participates in translational
      regulation during oogenesis via the cap-binding complex. This is a downstream
      developmental role, not a core function.
    supported_by:
    - reference_id: PMID:19101615
      supporting_text: lowering Hsp90 activity enhances the oogenesis alterations
        linked to diverse cup mutant alleles
- term:
    id: GO:0019094
    label: pole plasm mRNA localization
  evidence_type: IMP
  original_reference_id: PMID:17565952
  review:
    summary: IMP annotation from PMID:17565952. Genetic approaches show that Hsp83/Hsp90
      is a localization factor for nanos and pgc mRNAs. When Hsp90 function is partially
      compromised, nanos and pgc mRNA localization is disrupted while other pole plasm
      components are unaffected. The mechanism appears to involve Hsp90 chaperoning
      LKB1 kinase (for pgc) and other partners (for nos).
    action: KEEP_AS_NON_CORE
    reason: This is a specific developmental role of Hsp83 in mRNA localization during
      embryogenesis, likely mediated through its chaperone function on LKB1 kinase
      and other clients. Non-core pleiotropic effect.
    supported_by:
    - reference_id: PMID:17565952
      supporting_text: the Hsp90 chaperone (encoded by Hsp83 in Drosophila) is a localization
        factor for two mRNAs, nanos and pgc
    - reference_id: PMID:17565952
      supporting_text: levels of the LKB1 kinase are reduced in Hsp83 mutant egg chambers
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:10716925
  review:
    summary: IDA annotation from PMID:10716925. Mass spectrometry analysis of immunoisolated
      Drosophila centrosomes identified Hsp83. The association persists after microtubule
      depolymerizing drug treatment, indicating Hsp90 is a core centrosomal component.
    action: ACCEPT
    reason: Directly demonstrated by mass spectrometry of purified centrosomes and
      confirmed to be a core centrosomal component that persists after microtubule
      depolymerization.
    supported_by:
    - reference_id: PMID:10716925
      supporting_text: a fraction of the total Hsp90 pool is localized at the centrosome
        throughout the cell cycle
    - reference_id: PMID:10716925
      supporting_text: This association between Hsp90 and the centrosome can be observed
        in purified centrosomes and after treatment with microtubule depolymerizing
        drugs, two criteria normally used to define core centrosomal components
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: TAS
  original_reference_id: PMID:10716925
  review:
    summary: TAS annotation from PMID:10716925 which describes Hsp83 as "a member
      of the highly conserved Hsp90 family including chaperones known to maintain
      the activity of many proteins." The protein folding function is stated as established
      fact in the publication.
    action: ACCEPT
    reason: Correct. Protein folding is the core function. Redundant with IBA, IEA,
      and ISS evidence.
    supported_by:
    - reference_id: PMID:10716925
      supporting_text: a member of the highly conserved Hsp90 family including chaperones
        known to maintain the activity of many proteins
- term:
    id: GO:0007098
    label: centrosome cycle
  evidence_type: IMP
  original_reference_id: PMID:10716925
  review:
    summary: IMP annotation from PMID:10716925. Disruption of Hsp90 function by mutations
      in Hsp83 or geldanamycin treatment results in abnormal centrosome separation
      and maturation, aberrant spindles, and impaired chromosome segregation.
    action: KEEP_AS_NON_CORE
    reason: Centrosome cycle involvement is a downstream consequence of Hsp83 chaperone
      function on centrosome client proteins. Hsp90 is required for proper centrosome
      function, but this is a pleiotropic effect of its core chaperone activity.
    supported_by:
    - reference_id: PMID:10716925
      supporting_text: Disruption of Hsp90 function by mutations in the Drosophila
        gene or treatment of mammalian cells with the Hsp90 inhibitor geldanamycin,
        results in abnormal centrosome separation and maturation, aberrant spindles
        and impaired chromosome segregation
- term:
    id: GO:0045187
    label: regulation of circadian sleep/wake cycle, sleep
  evidence_type: IMP
  original_reference_id: PMID:12015603
  review:
    summary: IMP annotation from PMID:12015603. Flies carrying a mutation for Hsp83
      showed exaggerated homeostatic sleep response and died after sleep deprivation,
      demonstrating that Hsp83 plays a protective role in sleep homeostasis.
    action: KEEP_AS_NON_CORE
    reason: Sleep regulation is a pleiotropic downstream effect. Hsp83 mutants show
      exaggerated homeostatic response to sleep deprivation, but this likely reflects
      a general stress-protective role rather than a direct sleep-regulatory function.
    supported_by:
    - reference_id: PMID:12015603
      supporting_text: flies carrying a mutation for the heat-shock protein Hsp83
        (Hsp83(08445)) showed exaggerated homeostatic response and died after sleep
        deprivation
- term:
    id: GO:0045187
    label: regulation of circadian sleep/wake cycle, sleep
  evidence_type: TAS
  original_reference_id: PMID:12486704
  review:
    summary: TAS annotation from PMID:12486704. This is a review article discussing
      sleep research in Drosophila and mouse, referencing the genetic approaches that
      identified Hsp83 mutants with sleep phenotypes.
    action: KEEP_AS_NON_CORE
    reason: Consistent with the IMP annotation from PMID:12015603 for the same term.
      Sleep regulation is a non-core pleiotropic effect.
    supported_by:
    - reference_id: PMID:12486704
      supporting_text: studies in both the mouse and fly have begun to reveal tantalizing
        suggestions about the underlying principles that regulate sleep homeostasis
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  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:10716925
  title: Hsp90 is a core centrosomal component and is required at different stages
    of the centrosome cycle in Drosophila and vertebrates.
  findings:
  - statement: Hsp83 identified by mass spectrometry in purified Drosophila centrosomes
    supporting_text: "One of the proteins identified is Hsp83, a member of the highly conserved Hsp90 family including chaperones known to maintain the activity of many proteins"
  - statement: A fraction of total Hsp90 pool is localized at the centrosome throughout the cell cycle
    supporting_text: "a fraction of the total Hsp90 pool is localized at the centrosome throughout the cell cycle at different stages of development in Drosophila and vertebrates"
  - statement: Disruption of Hsp90 function causes abnormal centrosome separation and maturation
    supporting_text: "Disruption of Hsp90 function by mutations in the Drosophila gene or treatment of mammalian cells with the Hsp90 inhibitor geldanamycin, results in abnormal centrosome separation and maturation, aberrant spindles and impaired chromosome segregation"
- id: PMID:12015603
  title: Stress response genes protect against lethal effects of sleep deprivation
    in Drosophila.
  findings:
  - statement: Hsp83 mutants show exaggerated homeostatic sleep response and die after sleep deprivation
    supporting_text: "flies carrying a mutation for the heat-shock protein Hsp83 (Hsp83(08445)) showed exaggerated homeostatic response and died after sleep deprivation"
  - statement: Heat-shock genes protect against lethal effects of sleep deprivation
    supporting_text: "activating heat-shock genes before sleep deprivation rescued cyc(01) flies from its lethal effects"
- id: PMID:12486704
  title: 'Perchance to dream: solving the mystery of sleep through genetic analysis.'
  findings: []
- id: PMID:15946124
  title: Zn2+-induced reversible dissociation of subunit Rpn10/p54 of the Drosophila
    26 S proteasome.
  findings:
  - statement: Hsp82 identified by MS as the main Rpn10/p54-interacting protein after proteasome disassembly
    supporting_text: "Hsp82 (heat-shock protein 82) has been identified by MS as the main Rpn10/p54-interacting protein, suggesting its role in the reassembly of the 26 S proteasome after Zn2+ removal"
  - statement: Suggests Hsp83 role in reassembly of 26S proteasome
    supporting_text: "removal of Zn2+ is followed by reassociation of subunit Rpn10/p54 to the RP, reassembly of the 26 S proteasome and resumption of the peptidase activity"
- id: PMID:16313561
  title: Cold hardening and transcriptional change in Drosophila melanogaster.
  findings:
  - statement: Hsp83 transcript upregulated after cold hardening treatment
    supporting_text: "stress proteins, including Hsp23, Hsp26, Hsp83 and Frost as well as membrane-associated proteins may contribute to the cold hardening response"
- id: PMID:16595740
  title: Thermoprotection of synaptic transmission in a Drosophila heat shock factor
    mutant is accompanied by increased expression of Hsp83 and DnaJ-1.
  findings:
  - statement: Hsp83 protein levels increase after heat shock even in hsf4 mutants
    supporting_text: "increases in the levels of Hsp83 and DnaJ-1 proteins but not in the inducible form of Hsp70 were detected by Western blot analysis"
  - statement: Compensatory upregulation of constitutive Hsps provides thermoprotection
    supporting_text: "the compensatory upregulation of constitutively expressed Hsps, in the absence of the synthesis of the major inducible Hsp, Hsp70, could still provide substantial thermoprotection"
- id: PMID:17565952
  title: The molecular chaperone Hsp90 is required for mRNA localization in Drosophila
    melanogaster embryos.
  findings:
  - statement: Hsp83/Hsp90 is a localization factor for nanos and pgc mRNAs
    supporting_text: "the Hsp90 chaperone (encoded by Hsp83 in Drosophila) is a localization factor for two mRNAs, nanos and pgc"
  - statement: LKB1 kinase levels reduced in Hsp83 mutant egg chambers
    supporting_text: "levels of the LKB1 kinase are reduced in Hsp83 mutant egg chambers"
- id: PMID:18344983
  title: NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration.
  findings:
  - statement: NMNAT displays chaperone function similar to heat-shock proteins
    supporting_text: "NMNAT displays chaperone function both in biochemical assays and cultured cells, and it shares significant structural similarity with known chaperones"
  - statement: Hsp83 used as comparison/control in chaperone assays
    supporting_text: "it is upregulated in the brain upon overexpression of poly-glutamine expanded protein and recruited with the chaperone Hsp70 into protein aggregates"
- id: PMID:19101615
  title: The molecular chaperone Hsp90 is a component of the cap-binding complex and
    interacts with the translational repressor Cup during Drosophila oogenesis.
  findings:
  - statement: Hsp90 isolated as component of cap-binding complex
    supporting_text: "isolated the product of the Hsp83 gene, the evolutionarily conserved chaperone Hsp90, as a specific component of the cap-binding complex"
  - statement: Hsp90 interacts with translational repressor Cup
    supporting_text: "Hsp90 interacts in vitro with the translational repressor Cup"
  - statement: Hsp83 and cup interact genetically in oogenesis
    supporting_text: "lowering Hsp90 activity enhances the oogenesis alterations linked to diverse cup mutant alleles"
  - statement: Hsp90 and Cup co-localize in cytoplasm of germline cells
    supporting_text: "Hsp90 and Cup co-localize in the cytoplasm of the developing germ-line cells within the germarium"
- id: PMID:19144915
  title: Trithorax requires Hsp90 for maintenance of active chromatin at sites of gene
    expression.
  findings:
  - statement: Hsp90 interacts directly with Trithorax and cooperates at chromatin for maintaining active expression
    supporting_text: "Hsp90 cooperates with Trx at chromatin for maintaining the active expression state of targets like the Hox genes"
  - statement: Pharmacological inhibition of Hsp90 results in degradation of Trx and down-regulation of homeotic gene expression
    supporting_text: "Pharmacological inhibition of Hsp90 results in degradation of Trx and a concomitant down-regulation of homeotic gene expression"
- id: PMID:19317464
  title: Mapping organelle proteins and protein complexes in Drosophila melanogaster.
  findings:
  - statement: LOPIT proteomics maps Hsp83 subcellular distribution in Drosophila embryos
    supporting_text: "we apply LOPIT, a mass-spectrometry based technique that simultaneously maps proteins to specific subcellular compartments, to Drosophila embryos"
- id: PMID:22099462
  title: XPORT-dependent transport of TRP and rhodopsin.
  findings:
  - statement: XPORT interacts with TRP, Rh1, Hsp27, and Hsp90 as part of ER chaperone function
    supporting_text: "XPORT is a resident ER and secretory pathway protein that interacts with TRP and Rh1, as well as with Hsp27 and Hsp90"
  - statement: XPORT promotes targeting of TRP to the membrane in Drosophila S2 cells
    supporting_text: "XPORT promotes the targeting of TRP to the membrane in Drosophila S2 cells"
- id: PMID:22579285
  title: Hsp90 globally targets paused RNA polymerase to regulate gene expression
    in response to environmental stimuli.
  findings:
  - statement: Hsp90 localizes to promoters of many genes
    supporting_text: "It localizes near promoters of many coding and noncoding genes including microRNAs"
  - statement: Hsp90 stabilizes NELF complex to maintain RNA Pol II pausing
    supporting_text: "Hsp90 maintains and optimizes RNA polymerase II pausing via stabilization of the negative elongation factor complex (NELF)"
  - statement: Hsp90 inhibition leads to upregulation of target genes
    supporting_text: "Inhibition of Hsp90 leads to upregulation of target genes"
- id: PMID:22902557
  title: The cochaperone shutdown defines a group of biogenesis factors essential for
    all piRNA populations in Drosophila.
  findings:
  - statement: Hsp83 interacts with cochaperone Shutdown (Shu)
    supporting_text: "unloaded AGO3 that localizes to cytoplasmic foci interacts with Hsp83"
  - statement: Required for piRNA biogenesis
    supporting_text: "our genetic and cell biological data point toward an important role for the Hsp83 machinery in piRNA biogenesis"
  - statement: Hsp83 enriched in peri-nuclear rim in wild-type nurse cells
    supporting_text: "Hsp83 was enriched in a peri-nuclear rim, potentially reflecting nuage accumulation"
- id: PMID:23509070
  title: The C8ORF38 homologue Sicily is a cytosolic chaperone for a mitochondrial
    complex I subunit.
  findings:
  - statement: Hsp83 forms complex with Sicily and ND42 for mitochondrial protein chaperoning
    supporting_text: "Sicily preprotein interacts with cytosolic Hsp90 to chaperone the CI subunit, ND42, before mitochondrial import"
  - statement: Hsp90 binds to Sicily directly and coimmunoprecipitates ND42 only when Sicily is coexpressed
    supporting_text: "Hsp90 binds to Sicily in an in vitro co-IP assay"
  - statement: Loss of Hsp90 leads to decreased levels of Sicily and CI subunits in vivo
    supporting_text: "flies expressing Hsp90 RNAi #1 exhibit severely decreased levels of Sicily, ND42, and NDUFS3 compared with controls"
- id: PMID:24086162
  title: The molecular chaperone Hsp90 is required for cell cycle exit in Drosophila
    melanogaster.
  findings:
  - statement: Hsp83 mutation causes increased E2F transcription and ectopic cell proliferation
    supporting_text: "Mutation of Hsp83, the Drosophila homolog of mammalian Hsp90, results in increased E2F-dependent transcription and ectopic cell proliferation in pupal tissues at a time when neighboring wild-type cells are postmitotic"
  - statement: APC/C targets accumulate in Hsp83 mutant cells
    supporting_text: "these Hsp83 mutant cells have increased Cyclin/Cdk activity and accumulate proteins normally targeted for proteolysis by the anaphase-promoting complex/cyclosome (APC/C)"
  - statement: Cdh1/Fzr proposed as an Hsp83 client protein
    supporting_text: "we propose that Cdh1/Fzr is a client protein of Hsp83"
- id: PMID:24292889
  title: Ube3a, the E3 ubiquitin ligase causing Angelman syndrome and linked to autism,
    regulates protein homeostasis through the proteasomal shuttle Rpn10.
  findings: []
- id: PMID:26896675
  title: A genome-wide resource for the analysis of protein localisation in Drosophila.
  findings:
  - statement: Genome-wide GFP tagging resource for protein localization
    supporting_text: "a genome-wide fosmid library of 10000 GFP-tagged clones, comprising tagged genes and most of their regulatory information"
- id: PMID:27979731
  title: "Nucleoporin Nup358 facilitates nuclear import of Methoprene-tolerant (Met)\
    \ in an importin \u03B2- and Hsp83-dependent manner."
  findings:
  - statement: Nup358 TPR domain interacts with Hsp83
    supporting_text: "a tetratricopeptide repeat (TPR) domain at the N-terminal end of Nup358 interacts with Hsp83 and is indispensable for Met nuclear localization"
  - statement: Interaction required for nuclear import of Met (JH receptor)
    supporting_text: "Nup358 facilitates JH-induced Met nuclear transport in a manner dependent on importin \u03B2 and Hsp83"
- id: PMID:29775584
  title: Conformational Activation of Argonaute by Distinct yet Coordinated Actions
    of the Hsp70 and Hsp90 Chaperone Systems.
  findings:
  - statement: Hsp90 system captures and stabilizes the open active form of Ago2
    supporting_text: "the Hsp90 system is required to extend the dwell time of Ago2 in the open state"
  - statement: Required for small RNA loading into Argonaute
    supporting_text: "Loading of small RNAs into Argonaute, the core protein in RNA silencing, requires the Hsp70/Hsp90 chaperone machinery"
  - statement: Hsp70 system expands structural ensembles, Hsp90 stabilizes active form
    supporting_text: "the Hsp70 system expands the structural ensembles of Ago2 and the Hsp90 system captures and stabilizes the active form"
- id: PMID:30193096
  title: Hsp90 Mediates Membrane Deformation and Exosome Release.
  findings:
  - statement: Hsp90 deforms membranes via amphipathic helix
    supporting_text: "Hsp90 also has the ability to directly interact with and deform membranes via an evolutionarily conserved amphipathic helix"
  - statement: Membrane function structurally separated from chaperone activity
    supporting_text: "we structurally separated the Hsp90 membrane-deforming function from its well-characterized chaperone activity"
  - statement: Open Hsp90 dimer exposes helix for MVB fusion
    supporting_text: "mutations and drugs that stabilize the open Hsp90 dimer expose the helix and allow MVB fusion"
- id: PMID:30245208
  title: Hsp83/Hsp90 Physically Associates with Insulin Receptor to Promote Neural Stem
    Cell Reactivation.
  findings:
  - statement: Hsp83 is both necessary and sufficient for NSC reactivation by promoting activation of InR pathway
    supporting_text: "Hsp83 is both necessary and sufficient for NSC reactivation by promoting the activation of InR pathway in larval brains in the presence of dietary amino acids"
  - statement: Both Hsp83 and its co-chaperone Cdc37 physically associate with InR
    supporting_text: "Both Hsp83 and its co-chaperone Cdc37 physically associate with InR"
- id: PMID:31907206
  title: Drosophila Morgana is an Hsp90-interacting protein with a direct role in
    microtubule polymerisation.
  findings:
  - statement: Morgana co-purifies with Hsp90-R2TP-TTT supercomplex
    supporting_text: "Mora localises to mitotic spindles and co-purifies with the Hsp90-R2TP-TTT supercomplex and with additional well-known Hsp90 co-chaperones"
  - statement: Mora localises to mitotic spindles
    supporting_text: "Drosophila Mora localises to mitotic spindles and co-purifies with the Hsp90-R2TP-TTT supercomplex"
- id: PMID:33176138
  title: Modulation of Ago2 Loading by Cyclophilin 40 Endows a Unique Repertoire of
    Functional miRNAs during Sperm Maturation in Drosophila.
  findings:
  - statement: Cyp40 interacts with duplex-incorporating Ago2 through Hsp90 in vitro
    supporting_text: "Cyp40 interacts with duplex-incorporating Ago2 through Hsp90 in vitro and selectively promotes the build-up of Ago2-bound miRNAs"
  - statement: Identifies RISC-regulatory roles for Hsp90 machinery
    supporting_text: "these results identify RISC-regulatory roles for Hsp90 machinery"
- id: PMID:21186352
  title: Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic variation.
  findings:
  - statement: Hsp83 interacts with Hop and Piwi
    supporting_text: "we isolated a protein complex composed of Hsp90, Piwi and Hop, the Hsp70/Hsp90 organizing protein homolog"
  - statement: Required for piRNA biogenesis and transposon suppression
    supporting_text: "Hsp90 and Hop regulate the piRNA pathway through Piwi to mediate canalization"
  - statement: Mediates developmental robustness via epigenetic silencing
    supporting_text: "epigenetic silencing of the expression of existing genetic variants and the suppression of transposon-induced new genetic variation as two major mechanisms underlying piRNA pathway-mediated canalization"
core_functions:
- description: The primary molecular function of Hsp83. As a member of the HSP90 family,
    Hsp83 binds near-native client proteins and uses its intrinsic ATPase activity
    to drive conformational changes that promote client maturation, activation, and
    stabilization. Known clients include kinases (insulin receptor, LKB1), transcription
    factors, Argonaute, APC/C components (Cdh1/Fzr), and centrosomal proteins.
  molecular_function:
    id: GO:0140662
    label: ATP-dependent protein folding chaperone
  directly_involved_in:
  - id: GO:0006457
    label: protein folding
  - id: GO:0050821
    label: protein stabilization
  - id: GO:0034605
    label: cellular response to heat
  - id: GO:0070922
    label: RISC complex assembly
  locations:
  - id: GO:0005829
    label: cytosol
  in_complex:
    id: GO:0101031
    label: protein folding chaperone complex
  supported_by:
  - reference_id: PMID:29775584
    supporting_text: the Hsp90 system is required to extend the dwell time of Ago2
      in the open state
  - reference_id: PMID:23509070
    supporting_text: Sicily preprotein interacts with cytosolic Hsp90 to chaperone
      the CI subunit, ND42, before mitochondrial import