Hsp90aa1

UniProt ID: P07901
Organism: Mus musculus
Review Status: COMPLETE
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Gene Description

Hsp90aa1 encodes the inducible cytosolic Hsp90-alpha molecular chaperone, an ATP-binding and ATP-hydrolyzing protein-folding chaperone that promotes maturation, stabilization, and regulation of selected client proteins. Hsp90aa1 functions as a dimer within dynamic co-chaperone/client complexes, cycles between ATP- and ADP-bound conformations, and is best curated with ATP-dependent protein folding chaperone, ATP hydrolysis, protein folding, protein stabilization, cytosol, and nucleus terms. Many additional GOA annotations describe specific client interactions, stress responses, secreted/membrane pools, neuronal contexts, or orthology-transferred phenotypes; these are retained as non-core or marked over-annotated when they are too generic or too indirect. Falcon deep research corroborates this core ATPase-driven cytosolic HSP90-alpha cycle, while treating extracellular HSP90-alpha, male-germline phenotypes, and individual client pathways as context-specific non-core biology unless a GOA annotation directly captures them.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0006457 protein folding
IBA
GO_REF:0000033
ACCEPT
Summary: protein folding is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0016887 ATP hydrolysis activity
IBA
GO_REF:0000033
ACCEPT
Summary: ATP hydrolysis activity is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0032991 protein-containing complex
IBA
GO_REF:0000033
MODIFY
Summary: Protein-containing complex is true but too generic for Hsp90aa1 chaperone complexes.
Reason: Use GO:0101031 protein folding chaperone complex for Hsp90 co-chaperone/client assemblies.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
functions as a dimer within dynamic co-chaperone/client complexes
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0005886 plasma membrane
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: plasma membrane is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
GO:0005524 ATP binding
IBA
GO_REF:0000033
ACCEPT
Summary: ATP binding is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0005829 cytosol
IBA
GO_REF:0000033
ACCEPT
Summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0005634 nucleus
IBA
GO_REF:0000033
ACCEPT
Summary: nucleus is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0050821 protein stabilization
IBA
GO_REF:0000033
ACCEPT
Summary: protein stabilization is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0034605 cellular response to heat
IBA
GO_REF:0000033
ACCEPT
Summary: cellular response to heat is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
GO:0051082 unfolded protein binding
IBA
GO_REF:0000033
MODIFY
Summary: Unfolded protein binding is not the best description of Hsp90aa1. Hsp90 is an ATP-dependent foldase for selected clients rather than a generic unfolded-protein holdase.
Reason: Replace with GO:0140662 ATP-dependent protein folding chaperone, which captures the ATP-driven Hsp90 mechanism.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0051082 unfolded protein binding is not the best term for Hsp90
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0043025 neuronal cell body
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: neuronal cell body is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0043209 myelin sheath
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: myelin sheath is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0048471 perinuclear region of cytoplasm
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: perinuclear region of cytoplasm is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0005524 ATP binding
IEA
GO_REF:0000120
ACCEPT
Summary: ATP binding is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0005634 nucleus
IEA
GO_REF:0000120
ACCEPT
Summary: nucleus is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0005737 cytoplasm
IEA
GO_REF:0000120
ACCEPT
Summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0005739 mitochondrion
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: mitochondrion is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0005886 plasma membrane
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: plasma membrane is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0006457 protein folding
IEA
GO_REF:0000002
ACCEPT
Summary: protein folding is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0016887 ATP hydrolysis activity
IEA
GO_REF:0000120
ACCEPT
Summary: ATP hydrolysis activity is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0032880 regulation of protein localization
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: regulation of protein localization is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0042470 melanosome
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: melanosome is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0044183 protein folding chaperone
IEA
GO_REF:0000117
ACCEPT
Summary: protein folding chaperone is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0044294 dendritic growth cone
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: dendritic growth cone is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0044295 axonal growth cone
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: axonal growth cone is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0051082 unfolded protein binding
IEA
GO_REF:0000002
MODIFY
Summary: Unfolded protein binding is not the best description of Hsp90aa1. Hsp90 is an ATP-dependent foldase for selected clients rather than a generic unfolded-protein holdase.
Reason: Replace with GO:0140662 ATP-dependent protein folding chaperone, which captures the ATP-driven Hsp90 mechanism.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0051082 unfolded protein binding is not the best term for Hsp90
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0140662 ATP-dependent protein folding chaperone
IEA
GO_REF:0000002
ACCEPT
Summary: ATP-dependent protein folding chaperone is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0005515 protein binding
IPI
PMID:18474241
The mammalian CHORD-containing protein melusin is a stress r...
MARK AS OVER ANNOTATED
Summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
Reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
The Hsp90 system’s specificity is heavily shaped by co-chaperones:
GO:0005515 protein binding
IPI
PMID:18566586
The mammalian target of rapamycin complex 2 controls folding...
MARK AS OVER ANNOTATED
Summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
Reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
The Hsp90 system’s specificity is heavily shaped by co-chaperones:
GO:0001764 neuron migration
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: neuron migration is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0002021 response to dietary excess
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: response to dietary excess is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0002134 UTP binding
IEA
GO_REF:0000107
REMOVE
Summary: UTP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding function.
Reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms overstates the evidence.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not supported
GO:0002135 CTP binding
IEA
GO_REF:0000107
REMOVE
Summary: CTP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding function.
Reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms overstates the evidence.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not supported
GO:0002218 activation of innate immune response
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: activation of innate immune response is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0002230 positive regulation of defense response to virus by host
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: positive regulation of defense response to virus by host is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0003009 skeletal muscle contraction
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: skeletal muscle contraction is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0003729 mRNA binding
IEA
GO_REF:0000107
MARK AS OVER ANNOTATED
Summary: mRNA binding is too broad or indirect to be informative for Hsp90aa1 curation.
Reason: The term does not distinguish Hsp90aa1 ATP-dependent chaperone activity from generic binding, complex membership, RNA association, or co-fractionation.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
GO:0005525 GTP binding
IEA
GO_REF:0000107
REMOVE
Summary: GTP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding function.
Reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms overstates the evidence.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not supported
GO:0005829 cytosol
IEA
GO_REF:0000120
ACCEPT
Summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0009410 response to xenobiotic stimulus
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: response to xenobiotic stimulus is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0009651 response to salt stress
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: response to salt stress is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0009986 cell surface
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: cell surface is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0010592 positive regulation of lamellipodium assembly
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: positive regulation of lamellipodium assembly is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0010659 cardiac muscle cell apoptotic process
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: cardiac muscle cell apoptotic process is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0010664 negative regulation of striated muscle cell apoptotic process
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: negative regulation of striated muscle cell apoptotic process is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0016323 basolateral plasma membrane
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: basolateral plasma membrane is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0016324 apical plasma membrane
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: apical plasma membrane is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
GO:0017098 sulfonylurea receptor binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: sulfonylurea receptor binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0019903 protein phosphatase binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: protein phosphatase binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0030150 protein import into mitochondrial matrix
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: protein import into mitochondrial matrix is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0030235 nitric-oxide synthase regulator activity
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: nitric-oxide synthase regulator activity is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0030911 TPR domain binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: TPR domain binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0031012 extracellular matrix
IEA
GO_REF:0000107
MARK AS OVER ANNOTATED
Summary: extracellular matrix is too broad or indirect to be informative for Hsp90aa1 curation.
Reason: The term does not distinguish Hsp90aa1 ATP-dependent chaperone activity from generic binding, complex membership, RNA association, or co-fractionation.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
GO:0031396 regulation of protein ubiquitination
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: regulation of protein ubiquitination is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0031526 brush border membrane
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: brush border membrane is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0031625 ubiquitin protein ligase binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: ubiquitin protein ligase binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0032273 positive regulation of protein polymerization
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: positive regulation of protein polymerization is a peripheral or orthology-transferred Hsp90-associated annotation rather than a core Hsp90aa1 function.
Reason: The annotation is not impossible for Hsp90 biology, but the evidence is indirect or context-specific compared with the core ATP-dependent chaperone function.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Many additional GOA annotations describe specific client interactions
GO:0032354 response to follicle-stimulating hormone
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: response to follicle-stimulating hormone is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0032564 dATP binding
IEA
GO_REF:0000107
REMOVE
Summary: dATP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding function.
Reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms overstates the evidence.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not supported
GO:0032728 positive regulation of interferon-beta production
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: positive regulation of interferon-beta production is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0032991 protein-containing complex
IEA
GO_REF:0000120
MODIFY
Summary: Protein-containing complex is true but too generic for Hsp90aa1 chaperone complexes.
Reason: Use GO:0101031 protein folding chaperone complex for Hsp90 co-chaperone/client assemblies.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
functions as a dimer within dynamic co-chaperone/client complexes
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0034605 cellular response to heat
IEA
GO_REF:0000120
ACCEPT
Summary: cellular response to heat is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
GO:0035900 response to isolation stress
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: response to isolation stress is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0036120 cellular response to platelet-derived growth factor stimulus
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: cellular response to platelet-derived growth factor stimulus is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0036126 sperm flagellum
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: sperm flagellum is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1-null males are sterile** due to a failure to produce sperm
GO:0042220 response to cocaine
IEA
GO_REF:0000107
MARK AS OVER ANNOTATED
Summary: IEA orthology projection (GO_REF:0000107, Ensembl Compara) of a drug-response term onto a general cytosolic/nuclear molecular chaperone. There is no Hsp90aa1-specific experimental evidence that "response to cocaine" reflects a distinct biological role of this gene; any involvement would be the generic chaperoning of a client protein, not a cocaine-response function.
Reason: Over-propagation by ortholog transfer onto a hub chaperone. HSP90 buffers thousands of clients, so projecting a single-species drug-response phenotype onto it adds no functional information and is not supported by direct Hsp90aa1 evidence. This mirrors the treatment of the identical IEA cocaine annotation on SMAD3 (also GO_REF:0000107), which is marked as over-annotated for the same reason.
GO:0042307 positive regulation of protein import into nucleus
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: positive regulation of protein import into nucleus is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0042802 identical protein binding
IEA
GO_REF:0000107
ACCEPT
Summary: identical protein binding is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0042803 protein homodimerization activity
IEA
GO_REF:0000107
ACCEPT
Summary: protein homodimerization activity is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0042826 histone deacetylase binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: histone deacetylase binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0042981 regulation of apoptotic process
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: regulation of apoptotic process is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0043025 neuronal cell body
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: neuronal cell body is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0043209 myelin sheath
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: myelin sheath is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0043627 response to estrogen
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: response to estrogen is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0044325 transmembrane transporter binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: transmembrane transporter binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0045732 positive regulation of protein catabolic process
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: positive regulation of protein catabolic process is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0045793 positive regulation of cell size
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: positive regulation of cell size is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0048156 tau protein binding
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: tau protein binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0048471 perinuclear region of cytoplasm
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: perinuclear region of cytoplasm is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0050821 protein stabilization
IEA
GO_REF:0000107
ACCEPT
Summary: protein stabilization is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0051020 GTPase binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: GTPase binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0051022 Rho GDP-dissociation inhibitor binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Rho GDP-dissociation inhibitor binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0051131 chaperone-mediated protein complex assembly
IEA
GO_REF:0000107
ACCEPT
Summary: chaperone-mediated protein complex assembly is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0051604 protein maturation
IEA
GO_REF:0000107
ACCEPT
Summary: protein maturation is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
GO:0060452 positive regulation of cardiac muscle contraction
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: positive regulation of cardiac muscle contraction is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0061771 response to caloric restriction
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: response to caloric restriction is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0070182 DNA polymerase binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: DNA polymerase binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0070301 cellular response to hydrogen peroxide
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: cellular response to hydrogen peroxide is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0071222 cellular response to lipopolysaccharide
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: cellular response to lipopolysaccharide is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0071260 cellular response to mechanical stimulus
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: cellular response to mechanical stimulus is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0071456 cellular response to hypoxia
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: cellular response to hypoxia is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α knockout causes a **dramatic reduction** in the normally high steady-state level of **HIF-1α in testis**
GO:0097110 scaffold protein binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: scaffold protein binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0097226 sperm mitochondrial sheath
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: sperm mitochondrial sheath is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1-null males are sterile** due to a failure to produce sperm
GO:0097524 sperm plasma membrane
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: sperm plasma membrane is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1-null males are sterile** due to a failure to produce sperm
GO:0097718 disordered domain specific binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: disordered domain specific binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0098586 cellular response to virus
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: cellular response to virus is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0099072 regulation of postsynaptic membrane neurotransmitter receptor levels
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: regulation of postsynaptic membrane neurotransmitter receptor levels is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0101031 protein folding chaperone complex
IEA
GO_REF:0000107
ACCEPT
Summary: protein folding chaperone complex is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:1902988 neurofibrillary tangle assembly
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: neurofibrillary tangle assembly is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:1905323 telomerase holoenzyme complex assembly
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: telomerase holoenzyme complex assembly is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:1990782 protein tyrosine kinase binding
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: protein tyrosine kinase binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0001764 neuron migration
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: neuron migration is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0002134 UTP binding
ISO
GO_REF:0000096
REMOVE
Summary: UTP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding function.
Reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms overstates the evidence.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not supported
GO:0002135 CTP binding
ISO
GO_REF:0000096
REMOVE
Summary: CTP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding function.
Reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms overstates the evidence.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not supported
GO:0003729 mRNA binding
ISO
GO_REF:0000096
MARK AS OVER ANNOTATED
Summary: mRNA binding is too broad or indirect to be informative for Hsp90aa1 curation.
Reason: The term does not distinguish Hsp90aa1 ATP-dependent chaperone activity from generic binding, complex membership, RNA association, or co-fractionation.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
GO:0005524 ATP binding
ISO
GO_REF:0000096
ACCEPT
Summary: ATP binding is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0005524 ATP binding
ISO
GO_REF:0000119
ACCEPT
Summary: ATP binding is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0005525 GTP binding
ISO
GO_REF:0000096
REMOVE
Summary: GTP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding function.
Reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms overstates the evidence.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not supported
GO:0005634 nucleus
ISO
GO_REF:0000096
ACCEPT
Summary: nucleus is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0005737 cytoplasm
ISO
GO_REF:0000096
ACCEPT
Summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0005737 cytoplasm
ISO
GO_REF:0000119
ACCEPT
Summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0005739 mitochondrion
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: mitochondrion is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0005829 cytosol
ISO
GO_REF:0000119
ACCEPT
Summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0009986 cell surface
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: cell surface is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
GO:0010592 positive regulation of lamellipodium assembly
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: positive regulation of lamellipodium assembly is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0010664 negative regulation of striated muscle cell apoptotic process
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: negative regulation of striated muscle cell apoptotic process is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0016323 basolateral plasma membrane
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: basolateral plasma membrane is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
GO:0016324 apical plasma membrane
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: apical plasma membrane is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
GO:0016887 ATP hydrolysis activity
ISO
GO_REF:0000119
ACCEPT
Summary: ATP hydrolysis activity is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0017098 sulfonylurea receptor binding
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: sulfonylurea receptor binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0019903 protein phosphatase binding
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: protein phosphatase binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0030235 nitric-oxide synthase regulator activity
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: nitric-oxide synthase regulator activity is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0030911 TPR domain binding
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: TPR domain binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0031012 extracellular matrix
ISO
GO_REF:0000096
MARK AS OVER ANNOTATED
Summary: extracellular matrix is too broad or indirect to be informative for Hsp90aa1 curation.
Reason: The term does not distinguish Hsp90aa1 ATP-dependent chaperone activity from generic binding, complex membership, RNA association, or co-fractionation.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
GO:0031526 brush border membrane
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: brush border membrane is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0031625 ubiquitin protein ligase binding
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: ubiquitin protein ligase binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0032564 dATP binding
ISO
GO_REF:0000096
REMOVE
Summary: dATP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding function.
Reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms overstates the evidence.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not supported
GO:0032991 protein-containing complex
ISO
GO_REF:0000096
MODIFY
Summary: Protein-containing complex is true but too generic for Hsp90aa1 chaperone complexes.
Reason: Use GO:0101031 protein folding chaperone complex for Hsp90 co-chaperone/client assemblies.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
functions as a dimer within dynamic co-chaperone/client complexes
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0032991 protein-containing complex
ISO
GO_REF:0000119
MODIFY
Summary: Protein-containing complex is true but too generic for Hsp90aa1 chaperone complexes.
Reason: Use GO:0101031 protein folding chaperone complex for Hsp90 co-chaperone/client assemblies.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
functions as a dimer within dynamic co-chaperone/client complexes
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0036126 sperm flagellum
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: sperm flagellum is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1-null males are sterile** due to a failure to produce sperm
GO:0042307 positive regulation of protein import into nucleus
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: positive regulation of protein import into nucleus is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0042802 identical protein binding
ISO
GO_REF:0000119
ACCEPT
Summary: identical protein binding is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0042803 protein homodimerization activity
ISO
GO_REF:0000119
ACCEPT
Summary: protein homodimerization activity is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0042826 histone deacetylase binding
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: histone deacetylase binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0043025 neuronal cell body
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: neuronal cell body is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0043209 myelin sheath
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: myelin sheath is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0044325 transmembrane transporter binding
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: transmembrane transporter binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0045793 positive regulation of cell size
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: positive regulation of cell size is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0048156 tau protein binding
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: tau protein binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0048156 tau protein binding
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: tau protein binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0048471 perinuclear region of cytoplasm
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: perinuclear region of cytoplasm is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0051020 GTPase binding
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: GTPase binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0051022 Rho GDP-dissociation inhibitor binding
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: Rho GDP-dissociation inhibitor binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0070182 DNA polymerase binding
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: DNA polymerase binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0097110 scaffold protein binding
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: scaffold protein binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0097226 sperm mitochondrial sheath
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: sperm mitochondrial sheath is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1-null males are sterile** due to a failure to produce sperm
GO:0097524 sperm plasma membrane
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: sperm plasma membrane is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1-null males are sterile** due to a failure to produce sperm
GO:0097718 disordered domain specific binding
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: disordered domain specific binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0099072 regulation of postsynaptic membrane neurotransmitter receptor levels
ISO
GO_REF:0000096
KEEP AS NON CORE
Summary: regulation of postsynaptic membrane neurotransmitter receptor levels is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0101031 protein folding chaperone complex
ISO
GO_REF:0000119
ACCEPT
Summary: protein folding chaperone complex is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0140767 enzyme-substrate adaptor activity
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: enzyme-substrate adaptor activity is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:1990782 protein tyrosine kinase binding
ISO
GO_REF:0000119
KEEP AS NON CORE
Summary: protein tyrosine kinase binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0005654 nucleoplasm
ISO
GO_REF:0000119
ACCEPT
Summary: nucleoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0044183 protein folding chaperone
IMP
PMID:24286867
Hsp90 activity is necessary to acquire a proper neuronal pol...
ACCEPT
Summary: protein folding chaperone is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0035651 AP-3 adaptor complex binding
IDA
PMID:19010779
Hermansky-Pudlak syndrome protein complexes associate with p...
REMOVE
Summary: AP-3 adaptor complex binding is not supported by the cached local evidence for PMID:19010779.
Reason: The cached PMID:19010779 text does not provide positive Hsp90aa1-specific evidence for AP-3 adaptor complex binding; generic cytosol/nucleus support is insufficient to retain this molecular interaction.
GO:0002218 activation of innate immune response
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: activation of innate immune response is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0002230 positive regulation of defense response to virus by host
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: positive regulation of defense response to virus by host is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0005739 mitochondrion
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: mitochondrion is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0032728 positive regulation of interferon-beta production
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: positive regulation of interferon-beta production is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0042981 regulation of apoptotic process
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: regulation of apoptotic process is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0098586 cellular response to virus
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: cellular response to virus is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0005515 protein binding
IPI
PMID:29916806
ZMYND10 functions in a chaperone relay during axonemal dynei...
MARK AS OVER ANNOTATED
Summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
Reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
The Hsp90 system’s specificity is heavily shaped by co-chaperones:
GO:0042802 identical protein binding
IPI
PMID:12885400
Identification of the nuclear receptor CAR:HSP90 complex in ...
ACCEPT
Summary: identical protein binding is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0005737 cytoplasm
IDA
PMID:27496612
Interaction of a Novel Chaperone PhLP2A With the Heat Shock ...
ACCEPT
Summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0006457 protein folding
IMP
PMID:27496612
Interaction of a Novel Chaperone PhLP2A With the Heat Shock ...
ACCEPT
Summary: protein folding is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0032991 protein-containing complex
IDA
PMID:27496612
Interaction of a Novel Chaperone PhLP2A With the Heat Shock ...
MODIFY
Summary: Protein-containing complex is true but too generic for Hsp90aa1 chaperone complexes.
Reason: Use GO:0101031 protein folding chaperone complex for Hsp90 co-chaperone/client assemblies.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
functions as a dimer within dynamic co-chaperone/client complexes
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0034605 cellular response to heat
IMP
PMID:27496612
Interaction of a Novel Chaperone PhLP2A With the Heat Shock ...
ACCEPT
Summary: cellular response to heat is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
GO:0044183 protein folding chaperone
IMP
PMID:27496612
Interaction of a Novel Chaperone PhLP2A With the Heat Shock ...
ACCEPT
Summary: protein folding chaperone is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0005515 protein binding
IPI
PMID:27686098
REV-ERBα influences the stability and nuclear localization o...
MARK AS OVER ANNOTATED
Summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
Reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
The Hsp90 system’s specificity is heavily shaped by co-chaperones:
GO:0005737 cytoplasm
IDA
PMID:27686098
REV-ERBα influences the stability and nuclear localization o...
ACCEPT
Summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0005515 protein binding
IPI
PMID:29127155
Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facil...
MARK AS OVER ANNOTATED
Summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
Reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
The Hsp90 system’s specificity is heavily shaped by co-chaperones:
GO:0032880 regulation of protein localization
IMP
PMID:24286867
Hsp90 activity is necessary to acquire a proper neuronal pol...
KEEP AS NON CORE
Summary: regulation of protein localization is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0043025 neuronal cell body
IDA
PMID:24286867
Hsp90 activity is necessary to acquire a proper neuronal pol...
KEEP AS NON CORE
Summary: neuronal cell body is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0044294 dendritic growth cone
IDA
PMID:24286867
Hsp90 activity is necessary to acquire a proper neuronal pol...
KEEP AS NON CORE
Summary: dendritic growth cone is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0044295 axonal growth cone
IDA
PMID:24286867
Hsp90 activity is necessary to acquire a proper neuronal pol...
KEEP AS NON CORE
Summary: axonal growth cone is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0048471 perinuclear region of cytoplasm
IDA
PMID:24286867
Hsp90 activity is necessary to acquire a proper neuronal pol...
KEEP AS NON CORE
Summary: perinuclear region of cytoplasm is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0005524 ATP binding
ISS
GO_REF:0000024
ACCEPT
Summary: ATP binding is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0046677 response to antibiotic
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: response to antibiotic is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0005515 protein binding
IPI
PMID:23184943
Dynamic nucleotide-dependent interactions of cysteine- and h...
MARK AS OVER ANNOTATED
Summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
Reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
The Hsp90 system’s specificity is heavily shaped by co-chaperones:
GO:0005634 nucleus
ISS
GO_REF:0000024
ACCEPT
Summary: nucleus is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0005737 cytoplasm
ISS
GO_REF:0000024
ACCEPT
Summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0009408 response to heat
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: response to heat is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0009409 response to cold
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: response to cold is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0005515 protein binding
IPI
PMID:22431752
Hectd1 regulates intracellular localization and secretion of...
MARK AS OVER ANNOTATED
Summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
Reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
The Hsp90 system’s specificity is heavily shaped by co-chaperones:
GO:0043209 myelin sheath
HDA
PMID:17634366
Proteolipid protein is required for transport of sirtuin 2 i...
KEEP AS NON CORE
Summary: myelin sheath is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0005829 cytosol
IDA
PMID:17923681
Mammalian Sir2 homolog SIRT3 regulates global mitochondrial ...
ACCEPT
Summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0005829 cytosol
TAS
Reactome:R-MMU-9646345
ACCEPT
Summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0005829 cytosol
TAS
Reactome:R-MMU-9646359
ACCEPT
Summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0005515 protein binding
IPI
PMID:23055941
RAB-like 2 has an essential role in male fertility, sperm in...
MARK AS OVER ANNOTATED
Summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
Reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
The Hsp90 system’s specificity is heavily shaped by co-chaperones:
GO:0005515 protein binding
IPI
PMID:12885400
Identification of the nuclear receptor CAR:HSP90 complex in ...
MARK AS OVER ANNOTATED
Summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
Reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
The Hsp90 system’s specificity is heavily shaped by co-chaperones:
GO:0005737 cytoplasm
IDA
PMID:17908927
A role for AGL ubiquitination in the glycogen storage disord...
ACCEPT
Summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0030911 TPR domain binding
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: TPR domain binding is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0006986 response to unfolded protein
TAS
PMID:12855682
Heat shock protein 90 as an endogenous protein enhancer of i...
KEEP AS NON CORE
Summary: response to unfolded protein is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0051082 unfolded protein binding
TAS
PMID:12855682
Heat shock protein 90 as an endogenous protein enhancer of i...
MODIFY
Summary: Unfolded protein binding is not the best description of Hsp90aa1. Hsp90 is an ATP-dependent foldase for selected clients rather than a generic unfolded-protein holdase.
Reason: Replace with GO:0140662 ATP-dependent protein folding chaperone, which captures the ATP-driven Hsp90 mechanism.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0051082 unfolded protein binding is not the best term for Hsp90
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0005515 protein binding
IPI
PMID:12855682
Heat shock protein 90 as an endogenous protein enhancer of i...
MARK AS OVER ANNOTATED
Summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
Reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
The Hsp90 system’s specificity is heavily shaped by co-chaperones:
GO:0005829 cytosol
TAS
PMID:12855682
Heat shock protein 90 as an endogenous protein enhancer of i...
ACCEPT
Summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
Reason: This term captures a central molecular activity, process, complex, or main localization of Hsp90aa1.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90α is a **cytosolic** Hsp90 isoform
GO:0006809 nitric oxide biosynthetic process
TAS
PMID:12855682
Heat shock protein 90 as an endogenous protein enhancer of i...
KEEP AS NON CORE
Summary: nitric oxide biosynthetic process is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0030235 nitric-oxide synthase regulator activity
IDA
PMID:12855682
Heat shock protein 90 as an endogenous protein enhancer of i...
KEEP AS NON CORE
Summary: nitric-oxide synthase regulator activity is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0042026 protein refolding
TAS
PMID:12855682
Heat shock protein 90 as an endogenous protein enhancer of i...
MODIFY
Summary: PMID:12855682 supports Hsp90-dependent iNOS/NO modulation, while UniProt and the Falcon synthesis support the general ATP-dependent chaperone cycle; the cited PMID does not support protein refolding specifically.
Reason: PMID:12855682 supports Hsp90-dependent modulation of iNOS/NO production, not protein refolding specifically. Replace with the core ATP-dependent protein-folding chaperone activity based on UniProt/Falcon support for the HSP90 ATPase-coupled chaperone cycle.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
GO:0045429 positive regulation of nitric oxide biosynthetic process
IDA
PMID:12855682
Heat shock protein 90 as an endogenous protein enhancer of i...
KEEP AS NON CORE
Summary: positive regulation of nitric oxide biosynthetic process is supported or plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core chaperone function.
Reason: Retain this annotation as context-specific while keeping the core review focused on ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
Supporting Evidence:
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations
GO:0045585 positive regulation of cytotoxic T cell differentiation
TAS
PMID:12855682
Heat shock protein 90 as an endogenous protein enhancer of i...
REMOVE
Summary: Positive regulation of cytotoxic T cell differentiation is not supported by PMID:12855682, which addresses iNOS-mediated nitric oxide production and cytotoxicity.
Reason: PMID:12855682 supports iNOS-mediated nitric oxide production and cytotoxicity, not cytotoxic T-cell differentiation. Generic Hsp90 location/function evidence does not support retaining this BP annotation.

Core Functions

Hsp90aa1 is an ATP-dependent protein-folding chaperone that uses ATP binding and hydrolysis to mature and stabilize selected client proteins in cytosolic and nuclear chaperone complexes.

Supporting Evidence:
  • file:mouse/Hsp90aa1/Hsp90aa1-notes.md
    Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone
  • file:mouse/Hsp90aa1/Hsp90aa1-notes.md
    Tsc1 facilitates "Hsp90-mediated folding of kinase and non-kinase clients"
  • file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
    **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer
  • file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
    ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release.
  • file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
    Hsp90α is a **cytosolic** Hsp90 isoform
  • file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
    Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**

References

Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
Combined Automated Annotation using Multiple IEA Methods
Heat shock protein 90 as an endogenous protein enhancer of inducible nitric-oxide synthase.
Identification of the nuclear receptor CAR:HSP90 complex in mouse liver and recruitment of protein phosphatase 2A in response to phenobarbital.
Proteolipid protein is required for transport of sirtuin 2 into CNS myelin.
A role for AGL ubiquitination in the glycogen storage disorders of Lafora and Cori's disease.
Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation.
The mammalian CHORD-containing protein melusin is a stress response protein interacting with Hsp90 and Sgt1.
The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C.
Hermansky-Pudlak syndrome protein complexes associate with phosphatidylinositol 4-kinase type II alpha in neuronal and non-neuronal cells.
Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme.
RAB-like 2 has an essential role in male fertility, sperm intra-flagellar transport, and tail assembly.
Dynamic nucleotide-dependent interactions of cysteine- and histidine-rich domain (CHORD)-containing Hsp90 cochaperones Chp-1 and melusin with cochaperones PP5 and Sgt1.
Hsp90 activity is necessary to acquire a proper neuronal polarization.
Interaction of a Novel Chaperone PhLP2A With the Heat Shock Protein Hsp90.
REV-ERBα influences the stability and nuclear localization of the glucocorticoid receptor.
Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients.
ZMYND10 functions in a chaperone relay during axonemal dynein assembly.
Reactome:R-MMU-9646345
Ubiquitin binds Vcp:Hdac6:Hsp90:Hsf1
Reactome:R-MMU-9646359
PolyUb-Misfolded Proteins:Hdac6 dissociate from complex
file:mouse/Hsp90aa1/Hsp90aa1-notes.md
Hsp90aa1 curator notes
file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
Hsp90aa1 Falcon deep research report
  • Hsp90aa1 encodes cytosolic HSP90-alpha, a dimeric ATP-dependent molecular chaperone.
    "**Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions as a dimer"
  • ATP binding and hydrolysis drive the HSP90-alpha chaperone cycle for client loading and maturation.
    "ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release."
  • HSP90-alpha is primarily cytosolic, with non-core extracellular and male-germline contexts.
    "Hsp90α is a **cytosolic** Hsp90 isoform"

Deep Research

Falcon

(Hsp90aa1-deep-research-falcon.md)
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 36 citations 2026-05-03T14:40:38.891157

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Mouse Hsp90aa1 (HSP90α; UniProt P07901) — functional annotation

0) Target identity verification (critical)

The UniProt entry provided (P07901) describes heat shock protein HSP 90-alpha from Mus musculus, matching the mouse gene symbol Hsp90aa1 (also referred to as Hsp90α/Hsp90a) and belonging to the cytosolic Hsp90 family. Independent mammalian isoform reviews and mouse genetics papers consistently map Hsp90α to Hsp90aa1 and distinguish it from key paralogs: Hsp90β (Hsp90ab1; constitutive; essential in early development), Grp94 (Hsp90b1; ER-resident), and TRAP1 (mitochondrial). (maiti2022cytosolichsp90isoformspecific pages 1-2, maiti2022cytosolichsp90isoformspecific pages 2-4, grad2010themolecularchaperone pages 1-2)

1) Key concepts and definitions (current understanding)

1.1 What Hsp90aa1 encodes

Hsp90aa1 encodes HSP90α, a highly abundant ATP-dependent molecular chaperone that functions as a dimer and supports proteostasis by promoting the conformational maturation/stabilization of a large set of “client” proteins, particularly signaling proteins. (oostenhawle2023organismalrolesofa pages 1-3, minari2024newinsightsinto pages 19-22)

1.2 Domain organization and the ATPase-driven chaperone cycle

HSP90α has the canonical Hsp90 architecture consisting of an N-terminal domain (NTD) containing the ATP-binding pocket, a middle domain (MD) involved in client interactions and ATPase regulation, and a C-terminal domain (CTD) that mediates dimerization and co-chaperone interactions (often via the C-terminal motif recognized by TPR co-chaperones). ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release. (minari2024newinsightsinto pages 19-22, wang2026targetinghsp90in pages 2-3, oostenhawle2023organismalrolesofa pages 1-3)

A useful structural depiction of the domain architecture and an integrated view of the chaperone cycle with co-chaperones is shown in the cropped figures from a recent cryoEM-focused review. (minari2024newinsightsinto media df53a9bd, minari2024newinsightsinto media 3fc408a6)

1.3 Co-chaperones (machinery that confers client selectivity)

The Hsp90 system’s specificity is heavily shaped by co-chaperones:
- HOP/STI1 acts as an adaptor that can bridge Hsp70→Hsp90 client transfer (forming transfer complexes). (fedorov2025heatshockprotein pages 6-7)
- CDC37 is a kinase-directed co-chaperone that supports recruitment and maturation of a large fraction of kinase clients. (minari2024newinsightsinto pages 19-22, oostenhawle2023organismalrolesofa pages 1-3)
- AHA1 is a potent accelerator of Hsp90 ATPase activity, promoting conformational transitions and client processing. (blagg2024theroleof pages 1-2, oostenhawle2023organismalrolesofa pages 1-3)
- p23 stabilizes specific late maturation states (classically described in steroid receptor maturation complexes). (minari2024newinsightsinto pages 19-22)

1.4 Client classes and pathway roles

Across eukaryotes, Hsp90 clients are enriched for signal transduction proteins, with prominent client classes including protein kinases and steroid/nuclear hormone receptors; recent structural work captures Hsp90 complexes with kinase and glucocorticoid receptor maturation machinery, consistent with this central role in signaling regulation rather than a narrow enzymatic substrate reaction. (minari2024newinsightsinto pages 19-22, oostenhawle2023organismalrolesofa pages 1-3)

2) Recent developments and latest research (prioritizing 2023–2024)

2.1 CryoEM resolves structural plasticity and co-chaperone/client assemblies (2024)

A 2024 cryoEM-centered synthesis highlights how nucleotide state and co-chaperone binding shape Hsp90 conformations and assemblies, with structural snapshots including Hsp90:Cdc37:kinase and Hsp90:p23:glucocorticoid receptor complexes, strengthening mechanistic models of client loading and maturation. (minari2024newinsightsinto pages 19-22)

2.2 Organism-level roles and cell-nonautonomous proteostasis (2023)

A 2023 review emphasizes that Hsp90’s functions extend beyond intracellular folding to organism-level coordination of proteostasis and stress responses, while still centering the canonical ATP-dependent cycle and the roles of Cdc37, Aha1, and p23 in regulating Hsp90 ATP hydrolysis and client processing. (oostenhawle2023organismalrolesofa pages 1-3)

2.3 Co-chaperone targeting emerges as a refined intervention strategy (2024)

A 2024 review focused on AHA1 frames it as a key ATPase accelerator whose dysregulation can promote disease states and motivates strategies to disrupt Hsp90–AHA1 interactions rather than bluntly inhibiting all Hsp90 activity. (blagg2024theroleof pages 1-2)

3) Functional annotation in mouse: biological processes, localization, and mechanisms

3.1 Subcellular localization

Hsp90α is a cytosolic Hsp90 isoform (with some functions connected to nuclear client biology via client trafficking), and is distinct from ER-localized Grp94/Hsp90b1 and mitochondrial TRAP1. (maiti2022cytosolichsp90isoformspecific pages 1-2, maiti2022cytosolichsp90isoformspecific pages 2-4)

3.2 Mouse genetics: viability vs a specific essential role in spermatogenesis

Multiple mouse studies converge on a striking phenotype: Hsp90aa1/Hsp90α is not required for organismal viability, but is essential for male fertility.
- Hsp90aa1-null males are sterile due to a failure to produce sperm, with spermatogenesis arrest at the pachytene stage of meiosis I and progressive germ cell loss leading to seminiferous tubule depletion/azoospermia. (grad2010themolecularchaperone pages 1-2, grad2010themolecularchaperone pages 7-8)
- Pharmacologic Hsp90 inhibition during the first wave of spermatogenesis (pubertal window) can partially phenocopy aspects of this defect; one quantified observation was ~25% smaller testes than controls (n=6 treated, n=5 control; p=0.01) under a pubertal dosing regimen. (grad2010themolecularchaperone pages 7-8)

A key isoform contrast relevant to interpretation: cytosolic Hsp90β (Hsp90ab1) is described as essential for early mouse development, whereas Hsp90α is dispensable for viability but required for specific tissue function (male germline). (grad2010themolecularchaperone pages 1-2, maiti2022cytosolichsp90isoformspecific pages 8-10)

3.3 Specialized germline mechanisms: piRNA pathway and retrotransposon repression

Hsp90α has a specialized role in piRNA biogenesis and germline genome defense:
- Hsp90α mutation causes a large reduction of primary and secondary piRNAs and mislocalization of MIWI2, with affected piRNA sizes reported in the ~24–32 nt range. (ichiyanagi2014hsp90αplaysan pages 1-1)
- Retrotransposon repression is perturbed at least post-transcriptionally (e.g., L1-encoded protein increase is described in the same study’s summary). (ichiyanagi2014hsp90αplaysan pages 1-2)

3.4 A physiologic client example in testis: HIF-1α stabilization

A mechanistically informative client relationship is the stabilization of HIF-1α:
- Hsp90α knockout causes a dramatic reduction in the normally high steady-state level of HIF-1α in testis, supporting spermatogenesis in the hypoxic testicular environment; Hsp90α also supports hypoxia-induced HIF-1α accumulation in tumor cells in that study. (tang2021heatshockprotein90alpha pages 1-2, tang2021heatshockprotein90alpha pages 6-9)
- A synthesis review likewise summarizes that Hsp90α knockout reduces HIF-1α levels in testis and connects this to spermiogenesis requirements. (maiti2022cytosolichsp90isoformspecific pages 8-10)

4) Current applications and real-world implementations

4.1 Extracellular HSP90α (eHSP90α): wound repair and motility/invasion biology

A distinctive and widely exploited real-world axis is secreted/extracellular HSP90α (eHSP90α):
- Keratinocytes can massively release eHSP90α into the wound bed to promote wound repair; the wound-healing activity is described as not requiring ATPase activity or dimerization, implying a noncanonical extracellular mechanism. (maiti2022cytosolichsp90isoformspecific pages 11-12, maiti2022cytosolichsp90isoformspecific pages 10-11)
- eHSP90α is implicated in tumor invasion/metastasis programs (e.g., via LRP1/CD91 signaling and protease cascades such as uPA/MMP2), and is detectable in plasma/serum as a biomarker across cancer types. (liu2024hsp90αandcell pages 5-6, maiti2022cytosolichsp90isoformspecific pages 11-12)

4.2 HSP90 inhibition and chemical biology toolkits

A major implementation of Hsp90 biology is the extensive development of inhibitors and chemical probes:
- A high-authority 2023 Nature Reviews Molecular Cell Biology resource compiles inhibitors across NTD, MD, and CTD sites and highlights co-chaperone interface disruptors (e.g., HSP90–CDC37, HSP90–HOP, HSP90–AHA1), reflecting a shift toward more selective perturbations of the Hsp90 machinery. (chiosis2023structuralandfunctional pages 1-7)

5) Expert opinions and authoritative analysis (what experts emphasize)

5.1 Why pan-HSP90 inhibition has struggled clinically

A 2024 expert analysis argues that clinical failures cannot be attributed only to “drug quality,” but reflect isoform-specific biology and dramatic tissue-to-tissue variation in Hsp90 abundance, complicating both toxicity biomarkers and maximum tolerated dose definitions. The authors report that Hsp90β depletion underlies dose-limiting toxicities, whereas Hsp90α can buffer inhibitor penetration (higher Hsp90α correlating with reduced host toxicity). (chang2024previouslyunrecognizedand pages 1-2)

5.2 Future direction: isoform-selective, PPI/co-chaperone targeting, and combination regimens

A broad clinical-development synthesis describes a historical progression from pan-isoform ATPase inhibitors toward isoform-selective agents, protein–protein interaction/co-chaperone disruptors, and multi-specific strategies, reflecting expert consensus that refining selectivity is essential for therapeutic windows. (gu2025advancesinthe pages 16-16)

6) Relevant statistics and quantitative data (recent sources)

6.1 Abundance

Hsp90 is among the most abundant proteins in cells: one review reports ~1–2% of total cellular protein in healthy cells, increasing to ~4–6% under stress (or in transformed contexts). (blagg2024theroleof pages 1-2)

6.2 Mouse quantitative phenotype example

Pubertal pharmacologic Hsp90 inhibition produced testes ~25% smaller than controls (n=6 treated, n=5 control; p=0.01) in one mouse study, supporting that Hsp90 activity is functionally required during spermatogenic maturation windows. (grad2010themolecularchaperone pages 7-8)

6.3 Clinical trial landscape and outcomes

  • One 2024 review reports ~200 Hsp90 inhibitor monotherapy/combination trials since 1999 and at least 90 monotherapy trials, with no US FDA-approved systemic Hsp90 inhibitors noted there. (chang2024previouslyunrecognizedand pages 1-2)
  • A complementary clinical-development synthesis reports 33 HSP regulators entering 128 clinical trials (77 Phase I, 45 Phase II, 4 Phase III), with ~54% completed, ~40% suspended/terminated/withdrawn/unknown, and ~6% active/recruiting; ~98% of these trials were in cancer, and ~65% used single-agent designs. (gu2025advancesinthe pages 16-16)

6.4 Biomarker performance example

A 2024 cancer review reports that serum Hsp90α in gastric cancer achieved 52.50% sensitivity and 92.50% specificity in a cited diagnostic context, illustrating real-world diagnostic tradeoffs. (liu2024hsp90αandcell pages 5-6)

7) Practical functional-annotation summary (for databases/curation)

  • Molecular function: ATP-dependent molecular chaperone; promotes conformational maturation/stabilization of signaling clients via co-chaperone-regulated ATPase cycle. (minari2024newinsightsinto pages 19-22, oostenhawle2023organismalrolesofa pages 1-3)
  • Primary biological processes (mouse-relevant): male germline meiosis progression (pachytene→later), spermatogenesis; piRNA biogenesis and retrotransposon repression; hypoxia response via HIF-1α stabilization in testis. (grad2010themolecularchaperone pages 1-2, ichiyanagi2014hsp90αplaysan pages 1-1, tang2021heatshockprotein90alpha pages 1-2)
  • Localization: cytosol (canonical); specialized extracellular/secreted activity (eHSP90α) in wound repair and motility/invasion programs. (maiti2022cytosolichsp90isoformspecific pages 1-2, maiti2022cytosolichsp90isoformspecific pages 11-12)
  • Key pathways/complexes: Hsp70–HOP–Hsp90 client transfer; kinase maturation via CDC37; ATPase acceleration by AHA1; receptor maturation complexes stabilized by p23; extracellular eHSP90α signaling via LRP1/CD91 in repair and cancer. (fedorov2025heatshockprotein pages 6-7, minari2024newinsightsinto pages 19-22, blagg2024theroleof pages 1-2, liu2024hsp90αandcell pages 5-6)

Evidence map table

Topic Key points Representative sources (with year + URL when available)
Identity / paralogs Verified target: mouse Hsp90aa1 encodes cytosolic HSP90α, the stress-inducible Hsp90 isoform; distinct from cytosolic Hsp90β/Hsp90ab1 (constitutive, essential in early development), ER Grp94/Hsp90b1, and mitochondrial TRAP1. Cytosolic α/β share high sequence identity but differ in inducibility, tissue bias, and some client dependence. Hsp90α is reported at ~732 aa; Hsp90β at ~724 aa. (grad2010themolecularchaperone pages 1-2, maiti2022cytosolichsp90isoformspecific pages 1-2, maiti2022cytosolichsp90isoformspecific pages 2-4, chaudhury2025thehsp90βisoform pages 1-2) Maiti & Picard 2022, Biomolecules, https://doi.org/10.3390/biom12091166 (maiti2022cytosolichsp90isoformspecific pages 1-2, maiti2022cytosolichsp90isoformspecific pages 2-4); Grad et al. 2010, PLoS ONE, https://doi.org/10.1371/journal.pone.0015770 (grad2010themolecularchaperone pages 1-2); Chaudhury et al. 2025, Med Res Rev, https://doi.org/10.1002/med.22114 (chaudhury2025thehsp90βisoform pages 1-2)
Domain architecture / ATPase cycle HSP90α is a homodimeric ATP-dependent molecular chaperone with N-terminal ATP-binding domain (NTD), middle domain (MD) for client interaction/catalysis, and C-terminal dimerization domain (CTD); ATP binding promotes N-terminal closure, ATP hydrolysis drives conformational cycling and client maturation/release. The chaperone cycle includes open, closed, ADP-bound, and nucleotide-free states resolved in recent structural work. (minari2024newinsightsinto pages 19-22, oostenhawle2023organismalrolesofa pages 1-3, wang2026targetinghsp90in pages 2-3) Minari et al. 2024, BioChem, https://doi.org/10.3390/biochem4020004 (minari2024newinsightsinto pages 19-22); van Oosten-Hawle 2023, Biomolecules, https://doi.org/10.3390/biom13020251 (oostenhawle2023organismalrolesofa pages 1-3); Wang et al. 2026, Mol Cancer, https://doi.org/10.1186/s12943-025-02559-5 (wang2026targetinghsp90in pages 2-3)
Key co-chaperones and roles HOP/STI1 bridges Hsp70-to-Hsp90 client transfer; CDC37 recruits/stabilizes kinase clients; AHA1 is a major ATPase activator that accelerates conformational transitions and hydrolysis; p23 stabilizes closed/maturation complexes, especially with steroid receptors. Recent cryo-EM reviews depict these as modular regulators of client loading, activation, and release. (blagg2024theroleof pages 1-2, minari2024newinsightsinto pages 19-22, oostenhawle2023organismalrolesofa pages 1-3, fedorov2025heatshockprotein pages 6-7, chiosis2023structuralandfunctional pages 1-7) Blagg & Catalfano 2024, Front Mol Neurosci, https://doi.org/10.3389/fnmol.2024.1509280 (blagg2024theroleof pages 1-2); Minari et al. 2024, https://doi.org/10.3390/biochem4020004 (minari2024newinsightsinto pages 19-22); van Oosten-Hawle 2023, https://doi.org/10.3390/biom13020251 (oostenhawle2023organismalrolesofa pages 1-3); Fedorov et al. 2025, Cells, https://doi.org/10.3390/cells14231837 (fedorov2025heatshockprotein pages 6-7); Chiosis et al. 2023, Nat Rev Mol Cell Biol, https://doi.org/10.1038/s41580-023-00640-9 (chiosis2023structuralandfunctional pages 1-7)
Client classes / pathways HSP90α supports maturation/stability of broad signaling clients, especially protein kinases and steroid hormone receptors; representative pathway-linked clients include EGFR/HER2/BRAF, AKT/RAF/MET, and glucocorticoid receptor complexes. In mouse testis, a notable physiologic client relationship is HIF-1α stabilization by Hsp90α. Thus Hsp90aa1 functions broadly in proteostasis-linked signaling, cell survival, and developmental regulation rather than catalyzing a classic metabolic substrate reaction. (minari2024newinsightsinto pages 19-22, oostenhawle2023organismalrolesofa pages 1-3, wang2026targetinghsp90in pages 2-3, maiti2022cytosolichsp90isoformspecific pages 8-10, tang2021heatshockprotein90alpha pages 1-2) Minari et al. 2024, https://doi.org/10.3390/biochem4020004 (minari2024newinsightsinto pages 19-22); van Oosten-Hawle 2023, https://doi.org/10.3390/biom13020251 (oostenhawle2023organismalrolesofa pages 1-3); Tang et al. 2021, Cancer Gene Ther, https://doi.org/10.1038/s41417-021-00316-6 (tang2021heatshockprotein90alpha pages 1-2); Maiti & Picard 2022, https://doi.org/10.3390/biom12091166 (maiti2022cytosolichsp90isoformspecific pages 8-10)
Subcellular localization, including extracellular HSP90α Primary localization is cytosolic, with client-associated functions extending to the nucleus in some complexes; distinct family paralogs occupy ER (Grp94) and mitochondria (TRAP1). A major isoform-specific annotation is extracellular HSP90α (eHSP90α): secreted under stress/injury, acting through noncanonical extracellular signaling to promote cell migration, wound repair, invasion, angiogenesis, and ECM-remodeling programs. Wound-healing activity does not require ATPase activity or dimerization in the cited review. (maiti2022cytosolichsp90isoformspecific pages 1-2, maiti2022cytosolichsp90isoformspecific pages 11-12, maiti2022cytosolichsp90isoformspecific pages 19-21, maiti2022cytosolichsp90isoformspecific pages 10-11) Maiti & Picard 2022, https://doi.org/10.3390/biom12091166 (maiti2022cytosolichsp90isoformspecific pages 1-2, maiti2022cytosolichsp90isoformspecific pages 11-12, maiti2022cytosolichsp90isoformspecific pages 19-21, maiti2022cytosolichsp90isoformspecific pages 10-11)
Mouse KO phenotypes and quantified findings Global Hsp90aa1/Hsp90α loss is compatible with viability but causes male sterility due to failure of spermatogenesis, with arrest at/after pachytene of meiosis I and eventual azoospermia. Mechanistic mouse studies also show roles in piRNA biogenesis, MIWI2 localization, retrotransposon repression, and testicular HIF-1α stabilization. Quantified findings available in the gathered evidence: pharmacologic Hsp90 inhibition during the first wave of spermatogenesis produced testes ~25% smaller than controls (n=6 treated, n=5 control; p=0.01); Hsp90α mutant testes show a large reduction of 24–32-nt piRNAs and mislocalization of MIWI2; HIF-1α levels are described as dramatically reduced in Hsp90α-null testis. (maiti2022cytosolichsp90isoformspecific pages 8-10, tang2021heatshockprotein90alpha pages 1-2, grad2010themolecularchaperone pages 7-8, grad2010themolecularchaperone pages 1-2, ichiyanagi2014hsp90αplaysan pages 1-1) Grad et al. 2010, https://doi.org/10.1371/journal.pone.0015770 (grad2010themolecularchaperone pages 7-8, grad2010themolecularchaperone pages 1-2); Ichiyanagi et al. 2014, Nucleic Acids Res, https://doi.org/10.1093/nar/gku881 (ichiyanagi2014hsp90αplaysan pages 1-1); Tang et al. 2021, https://doi.org/10.1038/s41417-021-00316-6 (tang2021heatshockprotein90alpha pages 1-2); Maiti & Picard 2022, https://doi.org/10.3390/biom12091166 (maiti2022cytosolichsp90isoformspecific pages 8-10)
Translational applications and statistics Drug development: HSP90 is a major oncology target, but pan-HSP90 inhibitors have faced toxicity/efficacy limits; recent reviews emphasize domain-specific, co-chaperone-disrupting, and isoform-selective strategies. Reported statistics: Hsp90 constitutes ~1–2% of total protein in healthy cells and ~4–6% under stress/transformation; tumor cells average ~3–7% total Hsp90 versus ~2–3% in normal cells; since 1999 there have been ~200 monotherapy/combination HSP90 clinical trials, including at least 90 monotherapy trials, yet no FDA-approved systemic HSP90 inhibitor was noted in the cited 2024 review. In GI cancer, a 2023 systematic review identified 20 trials, with 17/20 performed before 2015. Biomarker: serum Hsp90α in gastric cancer showed 52.50% sensitivity and 92.50% specificity in the cited review. eHSP90α is also being explored as a prognostic biomarker and extracellular therapeutic target. (blagg2024theroleof pages 1-2, maiti2022cytosolichsp90isoformspecific pages 11-12, liu2024hsp90αandcell pages 5-6, chang2024previouslyunrecognizedand pages 1-2) Blagg & Catalfano 2024, https://doi.org/10.3389/fnmol.2024.1509280 (blagg2024theroleof pages 1-2); Maiti & Picard 2022, https://doi.org/10.3390/biom12091166 (maiti2022cytosolichsp90isoformspecific pages 11-12); Liu & Qian 2024, Discover Oncology, https://doi.org/10.1007/s12672-024-01021-0 (liu2024hsp90αandcell pages 5-6); Chang et al. 2024, Cell Stress Chaperones, https://doi.org/10.1016/j.cstres.2024.08.002 (chang2024previouslyunrecognizedand pages 1-2)

Table: This table summarizes core functional-annotation facts for mouse Hsp90aa1/HSP90α, including verified identity, mechanism, pathways, localization, mouse phenotypes, and translational relevance. It is designed as a compact evidence map for use in the final research report.

Notes on scope/limitations

  • The evidence gathered here verifies Hsp90aa1 ↔ Hsp90α and mouse phenotypes robustly, but the excerpts available do not directly quote the UniProt accession P07901; that accession was taken as provided by the user and cross-validated through gene/protein naming and isoform/paralog distinctions in the literature. (grad2010themolecularchaperone pages 1-2, maiti2022cytosolichsp90isoformspecific pages 1-2)

References

  1. (maiti2022cytosolichsp90isoformspecific pages 1-2): Samarpan Maiti and Didier Picard. Cytosolic hsp90 isoform-specific functions and clinical significance. Biomolecules, 12:1166, Aug 2022. URL: https://doi.org/10.3390/biom12091166, doi:10.3390/biom12091166. This article has 83 citations.

  2. (maiti2022cytosolichsp90isoformspecific pages 2-4): Samarpan Maiti and Didier Picard. Cytosolic hsp90 isoform-specific functions and clinical significance. Biomolecules, 12:1166, Aug 2022. URL: https://doi.org/10.3390/biom12091166, doi:10.3390/biom12091166. This article has 83 citations.

  3. (grad2010themolecularchaperone pages 1-2): Iwona Grad, Christopher R. Cederroth, Joël Walicki, Corinne Grey, Sofia Barluenga, Nicolas Winssinger, Bernard De Massy, Serge Nef, and Didier Picard. The molecular chaperone hsp90α is required for meiotic progression of spermatocytes beyond pachytene in the mouse. PLoS ONE, 5:e15770, Dec 2010. URL: https://doi.org/10.1371/journal.pone.0015770, doi:10.1371/journal.pone.0015770. This article has 201 citations and is from a peer-reviewed journal.

  4. (oostenhawle2023organismalrolesofa pages 1-3): Patricija van Oosten-Hawle. Organismal roles of hsp90. Biomolecules, 13:251, Jan 2023. URL: https://doi.org/10.3390/biom13020251, doi:10.3390/biom13020251. This article has 32 citations.

  5. (minari2024newinsightsinto pages 19-22): Karine Minari, Vitor Hugo Balasco Serrão, and Júlio César Borges. New insights into hsp90 structural plasticity revealed by cryoem. BioChem, 4:62-89, Apr 2024. URL: https://doi.org/10.3390/biochem4020004, doi:10.3390/biochem4020004. This article has 7 citations.

  6. (wang2026targetinghsp90in pages 2-3): Xueyi Wang, Ruiqing Ni, Xiaohui Wang, and Xun Li. Targeting hsp90 in cancer: advances in the development of inhibitors, mechanisms of action, and therapeutic applications. Molecular Cancer, Mar 2026. URL: https://doi.org/10.1186/s12943-025-02559-5, doi:10.1186/s12943-025-02559-5. This article has 1 citations and is from a highest quality peer-reviewed journal.

  7. (minari2024newinsightsinto media df53a9bd): Karine Minari, Vitor Hugo Balasco Serrão, and Júlio César Borges. New insights into hsp90 structural plasticity revealed by cryoem. BioChem, 4:62-89, Apr 2024. URL: https://doi.org/10.3390/biochem4020004, doi:10.3390/biochem4020004. This article has 7 citations.

  8. (minari2024newinsightsinto media 3fc408a6): Karine Minari, Vitor Hugo Balasco Serrão, and Júlio César Borges. New insights into hsp90 structural plasticity revealed by cryoem. BioChem, 4:62-89, Apr 2024. URL: https://doi.org/10.3390/biochem4020004, doi:10.3390/biochem4020004. This article has 7 citations.

  9. (fedorov2025heatshockprotein pages 6-7): Viacheslav Fedorov, Andrey Kurkin, Georgii Fofanov, Vitaliya Kaneva, Anna Kondratenko, Stephanie E. Combs, and Maxim Shevtsov. Heat shock protein chaperome is a multi-faceted vector for tumor cell migratory activity, invasion, and metastasis. Cells, 14:1837, Nov 2025. URL: https://doi.org/10.3390/cells14231837, doi:10.3390/cells14231837. This article has 0 citations.

  10. (blagg2024theroleof pages 1-2): Brian S. J. Blagg and Kevin C. Catalfano. The role of aha1 in cancer and neurodegeneration. Frontiers in Molecular Neuroscience, Dec 2024. URL: https://doi.org/10.3389/fnmol.2024.1509280, doi:10.3389/fnmol.2024.1509280. This article has 2 citations.

  11. (grad2010themolecularchaperone pages 7-8): Iwona Grad, Christopher R. Cederroth, Joël Walicki, Corinne Grey, Sofia Barluenga, Nicolas Winssinger, Bernard De Massy, Serge Nef, and Didier Picard. The molecular chaperone hsp90α is required for meiotic progression of spermatocytes beyond pachytene in the mouse. PLoS ONE, 5:e15770, Dec 2010. URL: https://doi.org/10.1371/journal.pone.0015770, doi:10.1371/journal.pone.0015770. This article has 201 citations and is from a peer-reviewed journal.

  12. (maiti2022cytosolichsp90isoformspecific pages 8-10): Samarpan Maiti and Didier Picard. Cytosolic hsp90 isoform-specific functions and clinical significance. Biomolecules, 12:1166, Aug 2022. URL: https://doi.org/10.3390/biom12091166, doi:10.3390/biom12091166. This article has 83 citations.

  13. (ichiyanagi2014hsp90αplaysan pages 1-1): Tomoko Ichiyanagi, Kenji Ichiyanagi, Ayako Ogawa, Satomi Kuramochi-Miyagawa, Toru Nakano, Shinichiro Chuma, Hiroyuki Sasaki, and Heiichiro Udono. Hsp90α plays an important role in pirna biogenesis and retrotransposon repression in mouse. Nucleic Acids Research, 42:11903-11911, Sep 2014. URL: https://doi.org/10.1093/nar/gku881, doi:10.1093/nar/gku881. This article has 52 citations and is from a highest quality peer-reviewed journal.

  14. (ichiyanagi2014hsp90αplaysan pages 1-2): Tomoko Ichiyanagi, Kenji Ichiyanagi, Ayako Ogawa, Satomi Kuramochi-Miyagawa, Toru Nakano, Shinichiro Chuma, Hiroyuki Sasaki, and Heiichiro Udono. Hsp90α plays an important role in pirna biogenesis and retrotransposon repression in mouse. Nucleic Acids Research, 42:11903-11911, Sep 2014. URL: https://doi.org/10.1093/nar/gku881, doi:10.1093/nar/gku881. This article has 52 citations and is from a highest quality peer-reviewed journal.

  15. (tang2021heatshockprotein90alpha pages 1-2): Xin Tang, Cheng Chang, Michelle Hao, Mei Chen, David T. Woodley, Axel H. Schönthal, and Wei Li. Heat shock protein-90alpha (hsp90α) stabilizes hypoxia-inducible factor-1α (hif-1α) in support of spermatogenesis and tumorigenesis. Cancer Gene Therapy, 28:1058-1070, Mar 2021. URL: https://doi.org/10.1038/s41417-021-00316-6, doi:10.1038/s41417-021-00316-6. This article has 51 citations and is from a peer-reviewed journal.

  16. (tang2021heatshockprotein90alpha pages 6-9): Xin Tang, Cheng Chang, Michelle Hao, Mei Chen, David T. Woodley, Axel H. Schönthal, and Wei Li. Heat shock protein-90alpha (hsp90α) stabilizes hypoxia-inducible factor-1α (hif-1α) in support of spermatogenesis and tumorigenesis. Cancer Gene Therapy, 28:1058-1070, Mar 2021. URL: https://doi.org/10.1038/s41417-021-00316-6, doi:10.1038/s41417-021-00316-6. This article has 51 citations and is from a peer-reviewed journal.

  17. (maiti2022cytosolichsp90isoformspecific pages 11-12): Samarpan Maiti and Didier Picard. Cytosolic hsp90 isoform-specific functions and clinical significance. Biomolecules, 12:1166, Aug 2022. URL: https://doi.org/10.3390/biom12091166, doi:10.3390/biom12091166. This article has 83 citations.

  18. (maiti2022cytosolichsp90isoformspecific pages 10-11): Samarpan Maiti and Didier Picard. Cytosolic hsp90 isoform-specific functions and clinical significance. Biomolecules, 12:1166, Aug 2022. URL: https://doi.org/10.3390/biom12091166, doi:10.3390/biom12091166. This article has 83 citations.

  19. (liu2024hsp90αandcell pages 5-6): Bin Liu and Daohai Qian. Hsp90α and cell death in cancers: a review. Discover Oncology, May 2024. URL: https://doi.org/10.1007/s12672-024-01021-0, doi:10.1007/s12672-024-01021-0. This article has 12 citations.

  20. (chiosis2023structuralandfunctional pages 1-7): Gabriela Chiosis, Chander S. Digwal, Jane B. Trepel, and Len Neckers. Structural and functional complexity of hsp90 in cellular homeostasis and disease. Nature Reviews Molecular Cell Biology, 24:797-815, Jul 2023. URL: https://doi.org/10.1038/s41580-023-00640-9, doi:10.1038/s41580-023-00640-9. This article has 194 citations and is from a domain leading peer-reviewed journal.

  21. (chang2024previouslyunrecognizedand pages 1-2): Cheng Chang, Xin Tang, David T. Woodley, Mei Chen, and Wei Li. Previously unrecognized and potentially consequential challenges facing hsp90 inhibitors in cancer clinical trials. Cell Stress and Chaperones, 29:642-653, Oct 2024. URL: https://doi.org/10.1016/j.cstres.2024.08.002, doi:10.1016/j.cstres.2024.08.002. This article has 9 citations and is from a peer-reviewed journal.

  22. (gu2025advancesinthe pages 16-16): Jinying Gu, Yanyi He, Chenxi He, Qiuyue Zhang, Qifei Huang, Shangjun Bai, Ruoning Wang, Qidong You, and Lei Wang. Advances in the structures, mechanisms and targeting of molecular chaperones. Signal Transduction and Targeted Therapy, Mar 2025. URL: https://doi.org/10.1038/s41392-025-02166-2, doi:10.1038/s41392-025-02166-2. This article has 63 citations and is from a peer-reviewed journal.

  23. (chaudhury2025thehsp90βisoform pages 1-2): Subhabrata Chaudhury, Terin D'Amico, and Brian S. J. Blagg. The hsp90β isoform: an attractive target for drug development. Medicinal Research Reviews, 45:1452-1465, Apr 2025. URL: https://doi.org/10.1002/med.22114, doi:10.1002/med.22114. This article has 11 citations and is from a domain leading peer-reviewed journal.

  24. (maiti2022cytosolichsp90isoformspecific pages 19-21): Samarpan Maiti and Didier Picard. Cytosolic hsp90 isoform-specific functions and clinical significance. Biomolecules, 12:1166, Aug 2022. URL: https://doi.org/10.3390/biom12091166, doi:10.3390/biom12091166. This article has 83 citations.

Citations

  1. fedorov2025heatshockprotein pages 6-7
  2. minari2024newinsightsinto pages 19-22
  3. oostenhawle2023organismalrolesofa pages 1-3
  4. blagg2024theroleof pages 1-2
  5. grad2010themolecularchaperone pages 7-8
  6. chiosis2023structuralandfunctional pages 1-7
  7. chang2024previouslyunrecognizedand pages 1-2
  8. gu2025advancesinthe pages 16-16
  9. grad2010themolecularchaperone pages 1-2
  10. https://doi.org/10.3390/biom12091166
  11. https://doi.org/10.1371/journal.pone.0015770
  12. https://doi.org/10.1002/med.22114
  13. https://doi.org/10.3390/biochem4020004
  14. https://doi.org/10.3390/biom13020251
  15. https://doi.org/10.1186/s12943-025-02559-5
  16. https://doi.org/10.3389/fnmol.2024.1509280
  17. https://doi.org/10.3390/cells14231837
  18. https://doi.org/10.1038/s41580-023-00640-9
  19. https://doi.org/10.1038/s41417-021-00316-6
  20. https://doi.org/10.1093/nar/gku881
  21. https://doi.org/10.1007/s12672-024-01021-0
  22. https://doi.org/10.1016/j.cstres.2024.08.002
  23. https://doi.org/10.3390/biom12091166,
  24. https://doi.org/10.1371/journal.pone.0015770,
  25. https://doi.org/10.3390/biom13020251,
  26. https://doi.org/10.3390/biochem4020004,
  27. https://doi.org/10.1186/s12943-025-02559-5,
  28. https://doi.org/10.3390/cells14231837,
  29. https://doi.org/10.3389/fnmol.2024.1509280,
  30. https://doi.org/10.1093/nar/gku881,
  31. https://doi.org/10.1038/s41417-021-00316-6,
  32. https://doi.org/10.1007/s12672-024-01021-0,
  33. https://doi.org/10.1038/s41580-023-00640-9,
  34. https://doi.org/10.1016/j.cstres.2024.08.002,
  35. https://doi.org/10.1038/s41392-025-02166-2,
  36. https://doi.org/10.1002/med.22114,

📚 Additional Documentation

Notes

(Hsp90aa1-notes.md)

Hsp90aa1 curation notes

Deep research status: just deep-research-falcon mouse Hsp90aa1 --timeout 1800 --fallback perplexity-lite completed on 2026-05-03 and created Hsp90aa1-deep-research-falcon.md. Earlier short-timeout Falcon attempts failed before the required long run was used.

Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent protein-folding chaperone. UniProt describes it as a "Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins" and links this cycle to ATPase activity.

Falcon synthesis: The Falcon report supports the same core function: Hsp90aa1 encodes cytosolic HSP90-alpha, a dimeric ATP-dependent molecular chaperone with an N-terminal ATP-binding domain, middle client-regulatory domain, and C-terminal dimerization/co-chaperone interaction domain. It emphasizes co-chaperone-regulated maturation and stabilization of selected signaling clients rather than generic protein binding [file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md "Hsp90aa1 encodes HSP90α, a highly abundant ATP-dependent molecular chaperone that functions as a dimer"; file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md "ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound states that orchestrate client loading, activation/maturation, and release"].

Falcon non-core context: The Falcon report also supports several context-specific annotations as non-core rather than core: extracellular HSP90-alpha in wound repair/migration programs, male germline phenotypes with spermatogenesis/piRNA effects, and HIF-1alpha client stabilization in testis [file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md "Hsp90α is a cytosolic Hsp90 isoform"; file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md "Keratinocytes can massively release eHSP90α into the wound bed"; file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md "Hsp90aa1-null males are sterile"].

ATPase evidence: UniProt lists catalytic activity "ATP + H2O = ADP + phosphate + H(+)" and notes that the Hsp90 cycle is linked to ATP binding and ATP hydrolysis. Tsc1/Aha1 experiments show cochaperone control of Hsp90 ATPase activity PMID:29127155.

Client-folding evidence: Tsc1 is described as "a new co-chaperone for Hsp90 that inhibits its ATPase activity" and the paper concludes that Tsc1 facilitates "Hsp90-mediated folding of kinase and non-kinase clients" PMID:29127155.

PhLP2A evidence: The PhLP2A study reports that "PhLP2A interacts directly with Hsp90" and that "PhLP2A forms complexes with Hsp90 which are mainly localized in the cytoplasm" PMID:27496612. This supports cytoplasmic chaperone-complex annotations.

Neuronal evidence: The neuronal-polarization study used Hsp90 inhibition and reports that "Hsp90 inhibition at different developmental stages disturbs neuronal polarity formation or axonal elongation" PMID:24286867. These annotations are context-specific and non-core because the evidence is inhibitor-based and not Hsp90aa1-isoform-specific.

Extracellular evidence: The Hectd1 study states that Hectd1 is a ubiquitin ligase substrate regulator for Hsp90 and that "Extracellular Hsp90 enhances migration of multiple cell types" PMID:22431752. Secreted or membrane-associated Hsp90 annotations should therefore be kept as non-core or marked over-annotated when the GO term implies a structural ECM location.

Nitric oxide evidence: The iNOS paper states that NO synthesis from iNOS "can be profoundly modulated by heat shock protein 90 (hsp90) through protein-protein interaction" and that Hsp90 increases iNOS activity PMID:12855682. This supports nitric-oxide-synthase regulator annotations as non-core client regulation.

Curation rule: GO:0051082 unfolded protein binding is not the best term for Hsp90; GO:0140662 ATP-dependent protein folding chaperone captures the ATP-driven Hsp90 foldase mechanism. GO:0005515 protein binding is too generic for Hsp90 client or cochaperone interactions.

Nucleotide specificity rule: Hsp90aa1 is an ATP-binding ATPase; GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not supported as core Hsp90aa1 nucleotide-binding functions and should be removed unless direct gene-specific evidence is available.

Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations. Plasma membrane, cell surface, extracellular, neuronal growth cone, myelin, sperm, and mitochondrial annotations can be context-specific but should not be treated as the core location of cytosolic Hsp90-alpha.

📄 View Raw YAML

id: P07901
gene_symbol: Hsp90aa1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: >-
  Hsp90aa1 encodes the inducible cytosolic Hsp90-alpha molecular chaperone, an ATP-binding and ATP-hydrolyzing
  protein-folding chaperone that promotes maturation, stabilization, and regulation of selected client
  proteins. Hsp90aa1 functions as a dimer within dynamic co-chaperone/client complexes, cycles between
  ATP- and ADP-bound conformations, and is best curated with ATP-dependent protein folding chaperone,
  ATP hydrolysis, protein folding, protein stabilization, cytosol, and nucleus terms. Many additional
  GOA annotations describe specific client interactions, stress responses, secreted/membrane pools, neuronal
  contexts, or orthology-transferred phenotypes; these are retained as non-core or marked over-annotated
  when they are too generic or too indirect. Falcon deep research corroborates this core ATPase-driven
  cytosolic HSP90-alpha cycle, while treating extracellular HSP90-alpha, male-germline phenotypes, and
  individual client pathways as context-specific non-core biology unless a GOA annotation directly captures
  them.
existing_annotations:
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: protein folding is consistent with the core ATP-dependent Hsp90 chaperone cycle and
      principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ATP hydrolysis activity is consistent with the core ATP-dependent Hsp90 chaperone cycle
      and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Protein-containing complex is true but too generic for Hsp90aa1 chaperone complexes.
    action: MODIFY
    reason: Use GO:0101031 protein folding chaperone complex for Hsp90 co-chaperone/client
      assemblies.
    proposed_replacement_terms:
    - id: GO:0101031
      label: protein folding chaperone complex
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: functions as a dimer within dynamic co-chaperone/client complexes
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: plasma membrane is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ATP binding is consistent with the core ATP-dependent Hsp90 chaperone cycle and
      principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: nucleus is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: protein stabilization is consistent with the core ATP-dependent Hsp90 chaperone cycle
      and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: cellular response to heat is consistent with the core ATP-dependent Hsp90 chaperone
      cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Unfolded protein binding is not the best description of Hsp90aa1. Hsp90 is an
      ATP-dependent foldase for selected clients rather than a generic unfolded-protein holdase.
    action: MODIFY
    reason: Replace with GO:0140662 ATP-dependent protein folding chaperone, which captures the
      ATP-driven Hsp90 mechanism.
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0051082 unfolded protein binding is not the best term for Hsp90
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: neuronal cell body is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0043209
    label: myelin sheath
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: myelin sheath is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: perinuclear region of cytoplasm is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ATP binding is consistent with the core ATP-dependent Hsp90 chaperone cycle and
      principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: nucleus is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: mitochondrion is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: plasma membrane is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: protein folding is consistent with the core ATP-dependent Hsp90 chaperone cycle and
      principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ATP hydrolysis activity is consistent with the core ATP-dependent Hsp90 chaperone cycle
      and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0032880
    label: regulation of protein localization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: regulation of protein localization is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0042470
    label: melanosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: melanosome is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: protein folding chaperone is consistent with the core ATP-dependent Hsp90 chaperone
      cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0044294
    label: dendritic growth cone
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: dendritic growth cone is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0044295
    label: axonal growth cone
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: axonal growth cone is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Unfolded protein binding is not the best description of Hsp90aa1. Hsp90 is an
      ATP-dependent foldase for selected clients rather than a generic unfolded-protein holdase.
    action: MODIFY
    reason: Replace with GO:0140662 ATP-dependent protein folding chaperone, which captures the
      ATP-driven Hsp90 mechanism.
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0051082 unfolded protein binding is not the best term for Hsp90
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0140662
    label: ATP-dependent protein folding chaperone
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: ATP-dependent protein folding chaperone is consistent with the core ATP-dependent Hsp90
      chaperone cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18474241
  review:
    summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is
      ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        The Hsp90 system’s specificity is heavily shaped by co-chaperones:
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18566586
  review:
    summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is
      ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        The Hsp90 system’s specificity is heavily shaped by co-chaperones:
- term:
    id: GO:0001764
    label: neuron migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: neuron migration is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0002021
    label: response to dietary excess
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to dietary excess is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0002134
    label: UTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: UTP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding
      function.
    action: REMOVE
    reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms
      overstates the evidence.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not
        supported
- term:
    id: GO:0002135
    label: CTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: CTP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding
      function.
    action: REMOVE
    reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms
      overstates the evidence.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not
        supported
- term:
    id: GO:0002218
    label: activation of innate immune response
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: activation of innate immune response is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0002230
    label: positive regulation of defense response to virus by host
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of defense response to virus by host is supported or plausible for
      a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the
      conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0003009
    label: skeletal muscle contraction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: skeletal muscle contraction is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0003729
    label: mRNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: mRNA binding is too broad or indirect to be informative for Hsp90aa1 curation.
    action: MARK_AS_OVER_ANNOTATED
    reason: The term does not distinguish Hsp90aa1 ATP-dependent chaperone activity from generic
      binding, complex membership, RNA association, or co-fractionation.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: GTP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding
      function.
    action: REMOVE
    reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms
      overstates the evidence.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not
        supported
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to xenobiotic stimulus is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0009651
    label: response to salt stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to salt stress is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cell surface is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0010592
    label: positive regulation of lamellipodium assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of lamellipodium assembly is supported or plausible for a specific
      Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core
      chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0010659
    label: cardiac muscle cell apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cardiac muscle cell apoptotic process is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0010664
    label: negative regulation of striated muscle cell apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: negative regulation of striated muscle cell apoptotic process is supported or plausible
      for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the
      conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: basolateral plasma membrane is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: apical plasma membrane is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
- term:
    id: GO:0017098
    label: sulfonylurea receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: sulfonylurea receptor binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0019903
    label: protein phosphatase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein phosphatase binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0030150
    label: protein import into mitochondrial matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein import into mitochondrial matrix is supported or plausible for a specific
      Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core
      chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0030235
    label: nitric-oxide synthase regulator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: nitric-oxide synthase regulator activity is supported or plausible for a specific
      Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core
      chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0030911
    label: TPR domain binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: TPR domain binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: extracellular matrix is too broad or indirect to be informative for Hsp90aa1 curation.
    action: MARK_AS_OVER_ANNOTATED
    reason: The term does not distinguish Hsp90aa1 ATP-dependent chaperone activity from generic
      binding, complex membership, RNA association, or co-fractionation.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
- term:
    id: GO:0031396
    label: regulation of protein ubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of protein ubiquitination is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0031526
    label: brush border membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: brush border membrane is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ubiquitin protein ligase binding is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0032273
    label: positive regulation of protein polymerization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of protein polymerization is a peripheral or orthology-transferred
      Hsp90-associated annotation rather than a core Hsp90aa1 function.
    action: KEEP_AS_NON_CORE
    reason: The annotation is not impossible for Hsp90 biology, but the evidence is indirect or
      context-specific compared with the core ATP-dependent chaperone function.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: Many additional GOA annotations describe specific client interactions
- term:
    id: GO:0032354
    label: response to follicle-stimulating hormone
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to follicle-stimulating hormone is supported or plausible for a specific
      Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core
      chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0032564
    label: dATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: dATP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding
      function.
    action: REMOVE
    reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms
      overstates the evidence.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not
        supported
- term:
    id: GO:0032728
    label: positive regulation of interferon-beta production
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of interferon-beta production is supported or plausible for a
      specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved
      core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Protein-containing complex is true but too generic for Hsp90aa1 chaperone complexes.
    action: MODIFY
    reason: Use GO:0101031 protein folding chaperone complex for Hsp90 co-chaperone/client
      assemblies.
    proposed_replacement_terms:
    - id: GO:0101031
      label: protein folding chaperone complex
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: functions as a dimer within dynamic co-chaperone/client complexes
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: cellular response to heat is consistent with the core ATP-dependent Hsp90 chaperone
      cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
- term:
    id: GO:0035900
    label: response to isolation stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to isolation stress is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0036120
    label: cellular response to platelet-derived growth factor stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to platelet-derived growth factor stimulus is supported or plausible
      for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the
      conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0036126
    label: sperm flagellum
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: sperm flagellum is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1-null males are sterile** due to a failure to produce sperm
- term:
    id: GO:0042220
    label: response to cocaine
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: IEA orthology projection (GO_REF:0000107, Ensembl Compara) of a drug-response
      term onto a general cytosolic/nuclear molecular chaperone. There is no Hsp90aa1-specific
      experimental evidence that "response to cocaine" reflects a distinct biological role of
      this gene; any involvement would be the generic chaperoning of a client protein, not a
      cocaine-response function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagation by ortholog transfer onto a hub chaperone. HSP90 buffers thousands
      of clients, so projecting a single-species drug-response phenotype onto it adds no
      functional information and is not supported by direct Hsp90aa1 evidence. This mirrors the
      treatment of the identical IEA cocaine annotation on SMAD3 (also GO_REF:0000107), which is
      marked as over-annotated for the same reason.
- term:
    id: GO:0042307
    label: positive regulation of protein import into nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of protein import into nucleus is supported or plausible for a
      specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved
      core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: identical protein binding is consistent with the core ATP-dependent Hsp90 chaperone
      cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein homodimerization activity is consistent with the core ATP-dependent Hsp90
      chaperone cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0042826
    label: histone deacetylase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: histone deacetylase binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of apoptotic process is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: neuronal cell body is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0043209
    label: myelin sheath
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: myelin sheath is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0043627
    label: response to estrogen
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to estrogen is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0044325
    label: transmembrane transporter binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: transmembrane transporter binding is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0045732
    label: positive regulation of protein catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of protein catabolic process is supported or plausible for a
      specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved
      core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0045793
    label: positive regulation of cell size
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of cell size is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0048156
    label: tau protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: tau protein binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: perinuclear region of cytoplasm is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein stabilization is consistent with the core ATP-dependent Hsp90 chaperone cycle
      and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0051020
    label: GTPase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: GTPase binding is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0051022
    label: Rho GDP-dissociation inhibitor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Rho GDP-dissociation inhibitor binding is supported or plausible for a specific
      Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core
      chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0051131
    label: chaperone-mediated protein complex assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: chaperone-mediated protein complex assembly is consistent with the core ATP-dependent
      Hsp90 chaperone cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0051604
    label: protein maturation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein maturation is consistent with the core ATP-dependent Hsp90 chaperone cycle and
      principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
- term:
    id: GO:0060452
    label: positive regulation of cardiac muscle contraction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: positive regulation of cardiac muscle contraction is supported or plausible for a
      specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved
      core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0061771
    label: response to caloric restriction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: response to caloric restriction is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0070182
    label: DNA polymerase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: DNA polymerase binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0070301
    label: cellular response to hydrogen peroxide
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to hydrogen peroxide is supported or plausible for a specific
      Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core
      chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0071222
    label: cellular response to lipopolysaccharide
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to lipopolysaccharide is supported or plausible for a specific
      Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core
      chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0071260
    label: cellular response to mechanical stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to mechanical stimulus is supported or plausible for a specific
      Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core
      chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0071456
    label: cellular response to hypoxia
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to hypoxia is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α knockout causes a **dramatic reduction** in the normally high steady-state level of **HIF-1α
        in testis**
- term:
    id: GO:0097110
    label: scaffold protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: scaffold protein binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0097226
    label: sperm mitochondrial sheath
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: sperm mitochondrial sheath is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1-null males are sterile** due to a failure to produce sperm
- term:
    id: GO:0097524
    label: sperm plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: sperm plasma membrane is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1-null males are sterile** due to a failure to produce sperm
- term:
    id: GO:0097718
    label: disordered domain specific binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: disordered domain specific binding is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0098586
    label: cellular response to virus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: cellular response to virus is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0099072
    label: regulation of postsynaptic membrane neurotransmitter receptor levels
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: regulation of postsynaptic membrane neurotransmitter receptor levels is supported or
      plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is
      not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0101031
    label: protein folding chaperone complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein folding chaperone complex is consistent with the core ATP-dependent Hsp90
      chaperone cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:1902988
    label: neurofibrillary tangle assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: neurofibrillary tangle assembly is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:1905323
    label: telomerase holoenzyme complex assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: telomerase holoenzyme complex assembly is supported or plausible for a specific
      Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core
      chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:1990782
    label: protein tyrosine kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: protein tyrosine kinase binding is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0001764
    label: neuron migration
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: neuron migration is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0002134
    label: UTP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: UTP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding
      function.
    action: REMOVE
    reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms
      overstates the evidence.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not
        supported
- term:
    id: GO:0002135
    label: CTP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: CTP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding
      function.
    action: REMOVE
    reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms
      overstates the evidence.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not
        supported
- term:
    id: GO:0003729
    label: mRNA binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: mRNA binding is too broad or indirect to be informative for Hsp90aa1 curation.
    action: MARK_AS_OVER_ANNOTATED
    reason: The term does not distinguish Hsp90aa1 ATP-dependent chaperone activity from generic
      binding, complex membership, RNA association, or co-fractionation.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: ATP binding is consistent with the core ATP-dependent Hsp90 chaperone cycle and
      principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: ATP binding is consistent with the core ATP-dependent Hsp90 chaperone cycle and
      principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: GTP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding
      function.
    action: REMOVE
    reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms
      overstates the evidence.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not
        supported
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: nucleus is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: mitochondrion is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: cell surface is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
- term:
    id: GO:0010592
    label: positive regulation of lamellipodium assembly
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of lamellipodium assembly is supported or plausible for a specific
      Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core
      chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0010664
    label: negative regulation of striated muscle cell apoptotic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: negative regulation of striated muscle cell apoptotic process is supported or plausible
      for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the
      conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0016323
    label: basolateral plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: basolateral plasma membrane is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: apical plasma membrane is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
- term:
    id: GO:0016887
    label: ATP hydrolysis activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: ATP hydrolysis activity is consistent with the core ATP-dependent Hsp90 chaperone cycle
      and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0017098
    label: sulfonylurea receptor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: sulfonylurea receptor binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0019903
    label: protein phosphatase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: protein phosphatase binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0030235
    label: nitric-oxide synthase regulator activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: nitric-oxide synthase regulator activity is supported or plausible for a specific
      Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core
      chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0030911
    label: TPR domain binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: TPR domain binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: extracellular matrix is too broad or indirect to be informative for Hsp90aa1 curation.
    action: MARK_AS_OVER_ANNOTATED
    reason: The term does not distinguish Hsp90aa1 ATP-dependent chaperone activity from generic
      binding, complex membership, RNA association, or co-fractionation.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
- term:
    id: GO:0031526
    label: brush border membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: brush border membrane is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: ubiquitin protein ligase binding is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0032564
    label: dATP binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: dATP binding is not supported as a biologically meaningful Hsp90aa1 nucleotide-binding
      function.
    action: REMOVE
    reason: Hsp90aa1 is an ATP-binding ATPase; automated transfer to other nucleotide-binding terms
      overstates the evidence.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GOA terms for UTP binding, CTP binding, GTP binding, and dATP binding are not
        supported
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Protein-containing complex is true but too generic for Hsp90aa1 chaperone complexes.
    action: MODIFY
    reason: Use GO:0101031 protein folding chaperone complex for Hsp90 co-chaperone/client
      assemblies.
    proposed_replacement_terms:
    - id: GO:0101031
      label: protein folding chaperone complex
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: functions as a dimer within dynamic co-chaperone/client complexes
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Protein-containing complex is true but too generic for Hsp90aa1 chaperone complexes.
    action: MODIFY
    reason: Use GO:0101031 protein folding chaperone complex for Hsp90 co-chaperone/client
      assemblies.
    proposed_replacement_terms:
    - id: GO:0101031
      label: protein folding chaperone complex
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: functions as a dimer within dynamic co-chaperone/client complexes
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0036126
    label: sperm flagellum
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: sperm flagellum is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1-null males are sterile** due to a failure to produce sperm
- term:
    id: GO:0042307
    label: positive regulation of protein import into nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of protein import into nucleus is supported or plausible for a
      specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved
      core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: identical protein binding is consistent with the core ATP-dependent Hsp90 chaperone
      cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein homodimerization activity is consistent with the core ATP-dependent Hsp90
      chaperone cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0042826
    label: histone deacetylase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: histone deacetylase binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: neuronal cell body is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0043209
    label: myelin sheath
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: myelin sheath is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0044325
    label: transmembrane transporter binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: transmembrane transporter binding is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0045793
    label: positive regulation of cell size
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: positive regulation of cell size is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0048156
    label: tau protein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: tau protein binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0048156
    label: tau protein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: tau protein binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: perinuclear region of cytoplasm is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0051020
    label: GTPase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: GTPase binding is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0051022
    label: Rho GDP-dissociation inhibitor binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Rho GDP-dissociation inhibitor binding is supported or plausible for a specific
      Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core
      chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0070182
    label: DNA polymerase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: DNA polymerase binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0097110
    label: scaffold protein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: scaffold protein binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0097226
    label: sperm mitochondrial sheath
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: sperm mitochondrial sheath is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1-null males are sterile** due to a failure to produce sperm
- term:
    id: GO:0097524
    label: sperm plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: sperm plasma membrane is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Keratinocytes can **massively release eHSP90α into the wound bed** to promote wound repair
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1-null males are sterile** due to a failure to produce sperm
- term:
    id: GO:0097718
    label: disordered domain specific binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: disordered domain specific binding is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0099072
    label: regulation of postsynaptic membrane neurotransmitter receptor levels
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: regulation of postsynaptic membrane neurotransmitter receptor levels is supported or
      plausible for a specific Hsp90aa1 client, localization, stress, or tissue context, but it is
      not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0101031
    label: protein folding chaperone complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein folding chaperone complex is consistent with the core ATP-dependent Hsp90
      chaperone cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0140767
    label: enzyme-substrate adaptor activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: enzyme-substrate adaptor activity is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:1990782
    label: protein tyrosine kinase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: protein tyrosine kinase binding is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: nucleoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and
      principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: IMP
  original_reference_id: PMID:24286867
  review:
    summary: protein folding chaperone is consistent with the core ATP-dependent Hsp90 chaperone
      cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0035651
    label: AP-3 adaptor complex binding
  evidence_type: IDA
  original_reference_id: PMID:19010779
  review:
    summary: AP-3 adaptor complex binding is not supported by the cached local evidence for
      PMID:19010779.
    action: REMOVE
    reason: The cached PMID:19010779 text does not provide positive Hsp90aa1-specific evidence for
      AP-3 adaptor complex binding; generic cytosol/nucleus support is insufficient to retain this
      molecular interaction.
- term:
    id: GO:0002218
    label: activation of innate immune response
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: activation of innate immune response is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0002230
    label: positive regulation of defense response to virus by host
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of defense response to virus by host is supported or plausible for
      a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the
      conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mitochondrion is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0032728
    label: positive regulation of interferon-beta production
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of interferon-beta production is supported or plausible for a
      specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved
      core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: regulation of apoptotic process is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0098586
    label: cellular response to virus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: cellular response to virus is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29916806
  review:
    summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is
      ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        The Hsp90 system’s specificity is heavily shaped by co-chaperones:
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:12885400
  review:
    summary: identical protein binding is consistent with the core ATP-dependent Hsp90 chaperone
      cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:27496612
  review:
    summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IMP
  original_reference_id: PMID:27496612
  review:
    summary: protein folding is consistent with the core ATP-dependent Hsp90 chaperone cycle and
      principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:27496612
  review:
    summary: Protein-containing complex is true but too generic for Hsp90aa1 chaperone complexes.
    action: MODIFY
    reason: Use GO:0101031 protein folding chaperone complex for Hsp90 co-chaperone/client
      assemblies.
    proposed_replacement_terms:
    - id: GO:0101031
      label: protein folding chaperone complex
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: functions as a dimer within dynamic co-chaperone/client complexes
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0034605
    label: cellular response to heat
  evidence_type: IMP
  original_reference_id: PMID:27496612
  review:
    summary: cellular response to heat is consistent with the core ATP-dependent Hsp90 chaperone
      cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: IMP
  original_reference_id: PMID:27496612
  review:
    summary: protein folding chaperone is consistent with the core ATP-dependent Hsp90 chaperone
      cycle and principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27686098
  review:
    summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is
      ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        The Hsp90 system’s specificity is heavily shaped by co-chaperones:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:27686098
  review:
    summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29127155
  review:
    summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is
      ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        The Hsp90 system’s specificity is heavily shaped by co-chaperones:
- term:
    id: GO:0032880
    label: regulation of protein localization
  evidence_type: IMP
  original_reference_id: PMID:24286867
  review:
    summary: regulation of protein localization is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IDA
  original_reference_id: PMID:24286867
  review:
    summary: neuronal cell body is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0044294
    label: dendritic growth cone
  evidence_type: IDA
  original_reference_id: PMID:24286867
  review:
    summary: dendritic growth cone is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0044295
    label: axonal growth cone
  evidence_type: IDA
  original_reference_id: PMID:24286867
  review:
    summary: axonal growth cone is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:24286867
  review:
    summary: perinuclear region of cytoplasm is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ATP binding is consistent with the core ATP-dependent Hsp90 chaperone cycle and
      principal cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0046677
    label: response to antibiotic
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: response to antibiotic is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23184943
  review:
    summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is
      ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        The Hsp90 system’s specificity is heavily shaped by co-chaperones:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: nucleus is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0009408
    label: response to heat
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: response to heat is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0009409
    label: response to cold
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: response to cold is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22431752
  review:
    summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is
      ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        The Hsp90 system’s specificity is heavily shaped by co-chaperones:
- term:
    id: GO:0043209
    label: myelin sheath
  evidence_type: HDA
  original_reference_id: PMID:17634366
  review:
    summary: myelin sheath is supported or plausible for a specific Hsp90aa1 client, localization,
      stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:17923681
  review:
    summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9646345
  review:
    summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-9646359
  review:
    summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23055941
  review:
    summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is
      ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        The Hsp90 system’s specificity is heavily shaped by co-chaperones:
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12885400
  review:
    summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is
      ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        The Hsp90 system’s specificity is heavily shaped by co-chaperones:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:17908927
  review:
    summary: cytoplasm is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0030911
    label: TPR domain binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: TPR domain binding is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0006986
    label: response to unfolded protein
  evidence_type: TAS
  original_reference_id: PMID:12855682
  review:
    summary: response to unfolded protein is supported or plausible for a specific Hsp90aa1 client,
      localization, stress, or tissue context, but it is not the conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: TAS
  original_reference_id: PMID:12855682
  review:
    summary: Unfolded protein binding is not the best description of Hsp90aa1. Hsp90 is an
      ATP-dependent foldase for selected clients rather than a generic unfolded-protein holdase.
    action: MODIFY
    reason: Replace with GO:0140662 ATP-dependent protein folding chaperone, which captures the
      ATP-driven Hsp90 mechanism.
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0051082 unfolded protein binding is not the best term for Hsp90
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12855682
  review:
    summary: Protein binding is an uninformative physical-interaction annotation for Hsp90aa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Hsp90 has many client and co-chaperone interactions; the useful functional call is
      ATP-dependent protein folding chaperone or a specific partner-binding term where justified.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: GO:0005515 protein binding is too generic for Hsp90 client or cochaperone
        interactions
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Across eukaryotes, Hsp90 clients are enriched for **signal transduction proteins**
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        The Hsp90 system’s specificity is heavily shaped by co-chaperones:
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: PMID:12855682
  review:
    summary: cytosol is consistent with the core ATP-dependent Hsp90 chaperone cycle and principal
      cytosolic/nuclear localization.
    action: ACCEPT
    reason: This term captures a central molecular activity, process, complex, or main localization
      of Hsp90aa1.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        Hsp90α is a **cytosolic** Hsp90 isoform
- term:
    id: GO:0006809
    label: nitric oxide biosynthetic process
  evidence_type: TAS
  original_reference_id: PMID:12855682
  review:
    summary: nitric oxide biosynthetic process is supported or plausible for a specific Hsp90aa1
      client, localization, stress, or tissue context, but it is not the conserved core chaperone
      function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0030235
    label: nitric-oxide synthase regulator activity
  evidence_type: IDA
  original_reference_id: PMID:12855682
  review:
    summary: nitric-oxide synthase regulator activity is supported or plausible for a specific
      Hsp90aa1 client, localization, stress, or tissue context, but it is not the conserved core
      chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: TAS
  original_reference_id: PMID:12855682
  review:
    summary: PMID:12855682 supports Hsp90-dependent iNOS/NO modulation, while UniProt
      and the Falcon synthesis support the general ATP-dependent chaperone cycle; the
      cited PMID does not support protein refolding specifically.
    action: MODIFY
    reason: PMID:12855682 supports Hsp90-dependent modulation of iNOS/NO production, not
      protein refolding specifically. Replace with the core ATP-dependent protein-folding
      chaperone activity based on UniProt/Falcon support for the HSP90 ATPase-coupled
      chaperone cycle.
    proposed_replacement_terms:
    - id: GO:0140662
      label: ATP-dependent protein folding chaperone
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
        protein-folding chaperone'
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
        as a dimer
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
      supporting_text: >-
        ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
        states that orchestrate client loading, activation/maturation, and release.
- term:
    id: GO:0045429
    label: positive regulation of nitric oxide biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:12855682
  review:
    summary: positive regulation of nitric oxide biosynthetic process is supported or plausible for
      a specific Hsp90aa1 client, localization, stress, or tissue context, but it is not the
      conserved core chaperone function.
    action: KEEP_AS_NON_CORE
    reason: Retain this annotation as context-specific while keeping the core review focused on
      ATP-dependent chaperone activity and cytosolic/nuclear chaperone complexes.
    supported_by:
    - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
      supporting_text: 'Core location rule: Cytosol/cytoplasm and nucleus are core Hsp90aa1 locations'
- term:
    id: GO:0045585
    label: positive regulation of cytotoxic T cell differentiation
  evidence_type: TAS
  original_reference_id: PMID:12855682
  review:
    summary: Positive regulation of cytotoxic T cell differentiation is not supported by
      PMID:12855682, which addresses iNOS-mediated nitric oxide production and cytotoxicity.
    action: REMOVE
    reason: PMID:12855682 supports iNOS-mediated nitric oxide production and cytotoxicity, not
      cytotoxic T-cell differentiation. Generic Hsp90 location/function evidence does not support
      retaining this BP annotation.
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: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:0000096
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-rat
    orthologs
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using
    Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000119
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-human
    orthologs
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:12855682
  title: Heat shock protein 90 as an endogenous protein enhancer of inducible nitric-oxide synthase.
  findings: []
- id: PMID:12885400
  title: Identification of the nuclear receptor CAR:HSP90 complex in mouse liver and recruitment of
    protein phosphatase 2A in response to phenobarbital.
  findings: []
- id: PMID:17634366
  title: Proteolipid protein is required for transport of sirtuin 2 into CNS myelin.
  findings: []
- id: PMID:17908927
  title: A role for AGL ubiquitination in the glycogen storage disorders of Lafora and Cori's
    disease.
  findings: []
- id: PMID:17923681
  title: Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation.
  findings: []
- id: PMID:18474241
  title: The mammalian CHORD-containing protein melusin is a stress response protein interacting
    with Hsp90 and Sgt1.
  findings: []
- id: PMID:18566586
  title: The mammalian target of rapamycin complex 2 controls folding and stability of Akt and
    protein kinase C.
  findings: []
- id: PMID:19010779
  title: Hermansky-Pudlak syndrome protein complexes associate with phosphatidylinositol 4-kinase
    type II alpha in neuronal and non-neuronal cells.
  findings: []
- id: PMID:22431752
  title: Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular
    behavior of the cranial mesenchyme.
  findings: []
- id: PMID:23055941
  title: RAB-like 2 has an essential role in male fertility, sperm intra-flagellar transport, and
    tail assembly.
  findings: []
- id: PMID:23184943
  title: Dynamic nucleotide-dependent interactions of cysteine- and histidine-rich domain
    (CHORD)-containing Hsp90 cochaperones Chp-1 and melusin with cochaperones PP5 and Sgt1.
  findings: []
- id: PMID:24286867
  title: Hsp90 activity is necessary to acquire a proper neuronal polarization.
  findings: []
- id: PMID:27496612
  title: Interaction of a Novel Chaperone PhLP2A With the Heat Shock Protein Hsp90.
  findings: []
- id: PMID:27686098
  title: REV-ERBα influences the stability and nuclear localization of the glucocorticoid receptor.
  findings: []
- id: PMID:29127155
  title: Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and
    non-kinase clients.
  findings: []
- id: PMID:29916806
  title: ZMYND10 functions in a chaperone relay during axonemal dynein assembly.
  findings: []
- id: Reactome:R-MMU-9646345
  title: Ubiquitin binds Vcp:Hdac6:Hsp90:Hsf1
  findings: []
- id: Reactome:R-MMU-9646359
  title: PolyUb-Misfolded Proteins:Hdac6 dissociate from complex
  findings: []
- id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
  title: Hsp90aa1 curator notes
  findings: []
- id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
  title: Hsp90aa1 Falcon deep research report
  findings:
  - statement: Hsp90aa1 encodes cytosolic HSP90-alpha, a dimeric ATP-dependent molecular chaperone.
    supporting_text: >-
      **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
      as a dimer
  - statement: ATP binding and hydrolysis drive the HSP90-alpha chaperone cycle for client loading
      and maturation.
    supporting_text: >-
      ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
      states that orchestrate client loading, activation/maturation, and release.
  - statement: HSP90-alpha is primarily cytosolic, with non-core extracellular and male-germline
      contexts.
    supporting_text: >-
      Hsp90α is a **cytosolic** Hsp90 isoform
core_functions:
- description: Hsp90aa1 is an ATP-dependent protein-folding chaperone that uses ATP binding and
    hydrolysis to mature and stabilize selected client proteins in cytosolic and nuclear chaperone
    complexes.
  supported_by:
  - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
    supporting_text: 'Core evidence: Hsp90aa1 is the inducible cytosolic/nuclear Hsp90-alpha ATP-dependent
      protein-folding chaperone'
  - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-notes.md
    supporting_text: Tsc1 facilitates "Hsp90-mediated folding of kinase and non-kinase clients"
  - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
    supporting_text: >-
      **Hsp90aa1 encodes HSP90α**, a highly abundant **ATP-dependent molecular chaperone** that functions
      as a dimer
  - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
    supporting_text: >-
      ATP binding and hydrolysis drive a conformational cycle through open/closed and nucleotide-bound
      states that orchestrate client loading, activation/maturation, and release.
  - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
    supporting_text: >-
      Hsp90α is a **cytosolic** Hsp90 isoform
  - reference_id: file:mouse/Hsp90aa1/Hsp90aa1-deep-research-falcon.md
    supporting_text: >-
      Across eukaryotes, Hsp90 clients are enriched for **signal transduction 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:0051131
    label: chaperone-mediated protein complex assembly
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005634
    label: nucleus
  in_complex:
    id: GO:0101031
    label: protein folding chaperone complex
proposed_new_terms: []
suggested_questions: []
suggested_experiments: []