Drosophila melanogaster Hsp23 is an alpha-crystallin-domain small heat shock protein with ATP-independent holdase activity. It protects unfolded clients against aggregation and preserves their ability to be refolded by other chaperones. Hsp23 is predominantly cytoplasmic, including neuronal cytoplasm and synaptic boutons; older imaging studies report heat-dependent nuclear or nucleolar redistribution, with antibody and preparation limitations. Hsp23 associates with Hsp26 and the SUMO-conjugating enzyme Ubc9. Its expression and protective effects vary with development and stress: it supports heat tolerance and proteostasis, and increased expression is associated with resistance to constant hypoxia. Hsp23/Hsp26 dosage also alters synapse number in developing motor neurons.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm is consistent with the conserved small heat shock protein function. Reason: Full PMID:32437379 identifies Hsp23 in the cytoplasm of CNS cells and synaptic boutons. This location is supported independently of the inherited assertion; conditional nuclear residence does not invalidate it. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000897708 SUPPORTS TRANSFER Actual PTHR45640 v19 target leaf PTN000163334 descends from this ancestral node. Current cytoplasm, heat-response and refolding IBDs are recovered with no loss on the target path. Target experimental descendants in WITH/FROM are valid grounding, not circularity. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Conditional nuclear localization is supported by primary imaging. Reason: The actual ancestral nucleus IBD lies on the Hsp23 lineage. Full PMID:6801431 reports nuclear immunofluorescence after 37C heat shock in salivary glands, preimmune controls and selective Hsp23 immunoprecipitation; recovery shifts staining to cytoplasm. Full 1986 DOI:10.1139/g86-152 independently reports nucleolar staining in heat-shocked Kc cells, while acknowledging possible Hsp26/27 cross-reaction in the imaging assay. These are positive target-directed observations with specificity/preparation caveats, not absence of nuclear evidence. Retain the contextual ancestral location without asserting exclusive or constitutive nuclear residence. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000897708 SUPPORTS TRANSFER Actual Hsp23 leaf PTN000163334 descends from current nucleus IBD. No loss is recovered. Target-directed 1981/1986 imaging provides independent positive contextual evidence, with antibody caveats. Supporting Evidence: PMID:6801431 Immunofluorescence microscopy showed the presence of hsp 23 preferentially in nuclei after heat shock |
| GO:0009408 response to heat | IBA GO_REF:0000033 | ACCEPT | Summary: Response to heat is consistent with the conserved small heat shock protein function. Reason: Heat induction and experimentally demonstrated client protection support the conserved heat-response function. Transcript induction alone is not the whole evidence: purified-client protection and stress phenotypes establish active chaperone work. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000897708 SUPPORTS TRANSFER Actual PTHR45640 v19 target leaf PTN000163334 descends from this ancestral node. Current cytoplasm, heat-response and refolding IBDs are recovered with no loss on the target path. Target experimental descendants in WITH/FROM are valid grounding, not circularity. Supporting Evidence: PMID:26705243 The four classical small HSPs (HSP22, HSP23, HSP26, and HSP27) were all highly induced after a heat shock |
| GO:0042026 protein refolding | IBA GO_REF:0000033 | ACCEPT | Summary: Protein refolding is consistent with the conserved small heat shock protein function. Reason: Hsp22 and Hsp23 bind heat-damaged clients, prevent aggregation and preserve a pool that the ATP-supplemented reticulocyte chaperone machinery can reactivate (full PMID:16572729). This is direct participation in the refolding process even though the small chaperone does not itself drive the later folding reaction. Actual target ancestry agrees with this inference. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000897708 SUPPORTS TRANSFER Actual PTHR45640 v19 target leaf PTN000163334 descends from this ancestral node. Current cytoplasm, heat-response and refolding IBDs are recovered with no loss on the target path. Target experimental descendants in WITH/FROM are valid grounding, not circularity. Supporting Evidence: PMID:16572729 Altogether, these results demonstrate that Hsp22, Hsp23, Hsp26, and Hsp27 can maintain heat-treated luciferase in a refoldable state, from which it can be refolded by other chaperones into an active enzyme. |
| GO:0051082 unfolded protein binding | IBA GO_REF:0000033 | MODIFY | Summary: Use the active holdase activity term for the demonstrated client-binding mechanism. Reason: Live QuickGO confirms that GO:0051082 is obsolete and GO:0140309 is active, named unfolded protein holdase activity. Its definition allows delivery to an acceptor molecule OR a specific location; it does not require transport between compartments. Full PMID:16572729 directly demonstrates client holding and later recovery by the reticulocyte chaperone machinery, with different efficiencies for each small Hsp. The active holdase term captures that activity; replacing the obsolete term with itself or awaiting a new term is unnecessary. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN000897708 SUPPORTS TRANSFER Actual target ancestry is verified. The frozen unfolded-protein-binding source assertion remains unchanged; that obsolete MF is absent from the current IBD extract, which is an ontology/version difference rather than evidence of functional loss. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:16572729 Altogether, these results demonstrate that Hsp22, Hsp23, Hsp26, and Hsp27 can maintain heat-treated luciferase in a refoldable state, from which it can be refolded by other chaperones into an active enzyme. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation from ARBA for cytoplasm localization. Consistent with IBA and IDA annotations for cytoplasm/cytosol. Redundant with better-evidenced annotations. Reason: This IEA annotation is consistent with the IBA and experimental (IDA cytosol) annotations. Acceptable as redundant support. |
| GO:0009408 response to heat | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation from ARBA for response to heat. Consistent with IBA and IDA annotations for the same term. Reason: This IEA annotation is consistent with the IDA and IBA annotations for the same term. Acceptable as redundant support. |
| GO:0042026 protein refolding | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation from ARBA for protein refolding. Consistent with IBA and IDA annotations. Reason: This IEA annotation is consistent with the IDA and IBA annotations for the same term. Acceptable as redundant support. |
| GO:0051082 unfolded protein binding | IEA GO_REF:0000117 | MODIFY | Summary: Use the active holdase activity term for the demonstrated client-binding mechanism. Reason: Live QuickGO confirms that GO:0051082 is obsolete and GO:0140309 is active, named unfolded protein holdase activity. Its definition allows delivery to an acceptor molecule OR a specific location; it does not require transport between compartments. Full PMID:16572729 directly demonstrates client holding and later recovery by the reticulocyte chaperone machinery, with different efficiencies for each small Hsp. The active holdase term captures that activity; replacing the obsolete term with itself or awaiting a new term is unnecessary. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:16572729 Altogether, these results demonstrate that Hsp22, Hsp23, Hsp26, and Hsp27 can maintain heat-treated luciferase in a refoldable state, from which it can be refolded by other chaperones into an active enzyme. |
| GO:0005515 protein binding | IPI PMID:38944040 Next-generation Drosophila protein interactome map and its f... | MODIFY | Summary: The Hsp26 association can be recorded as heat shock protein binding. Reason: The source interactome supplies a curated Hsp26 association; the full 2020 targeted study independently confirms Hsp23/Hsp26 co-immunoprecipitation with controls. GO:0031072 describes the binding partner more informatively than generic protein binding. This does not assert a fixed stoichiometry, obligatory complex or one-directional synapse phenotype. Proposed replacements: heat shock protein binding Supporting Evidence: PMID:32437379 These results confirm the physical interaction between sHSP23 and sHSP26 |
| GO:0006457 protein folding | IDA PMID:16572729 Differences in the chaperone-like activities of the four mai... | ACCEPT | Summary: IDA annotation for protein folding based on Morrow et al. 2006 demonstrating chaperone-like activity. All four Drosophila sHSPs prevent heat-induced protein aggregation and maintain proteins in a refoldable state (PMID:16572729). Reason: Hsp23 has demonstrated chaperone-like activity in preventing heat-induced protein aggregation and maintaining substrates in a refoldable state (PMID:16572729). Protein folding is an appropriate broad process annotation for a chaperone. Supporting Evidence: PMID:16572729 Therefore, the 4 main sHsps of Drosophila share the ability to prevent heat-induced protein aggregation and are able to maintain proteins in a refoldable state, although with different efficiencies file:DROME/Hsp23/Hsp23-deep-research-falcon.md frame Hsp23 as part of the **ATP-independent sHSP chaperone system** that buffers proteotoxic stress by limiting aggregation and helping maintain protein homeostasis |
| GO:0044183 protein folding chaperone | IDA PMID:16572729 Differences in the chaperone-like activities of the four mai... | MODIFY | Summary: Holdase activity is the more precise description of the source experiment. Reason: GO:0044183 does not define chaperones as necessarily ATP dependent. Its current comment distinguishes folding a client from holding it unfolded. Full PMID:16572729 demonstrates protection during heat treatment followed by reactivation by other chaperones in reticulocyte lysate plus ATP. GO:0140309 captures the small Hsp contribution specifically. Full PMID:26705243 excluded Hsp22 from cellular refolding assays and tested HSP70 knockdown for Hsp27 and CG14207, so those knockdown data should not be described as a direct Hsp22/Hsp23 requirement. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:16572729 Altogether, these results demonstrate that Hsp22, Hsp23, Hsp26, and Hsp27 can maintain heat-treated luciferase in a refoldable state, from which it can be refolded by other chaperones into an active enzyme. |
| GO:0005829 cytosol | IDA PMID:32437379 Small heat shock proteins determine synapse number and neuro... | ACCEPT | Summary: IDA annotation for cytosol localization based on Santana et al. (2020). Immunofluorescence in third instar larval brain shows that sHSP23 and sHSP26 localize in the cytoplasm of CNS cells (PMID:32437379). The more specific cytosol annotation is appropriate. Reason: Direct experimental evidence from immunofluorescence shows cytoplasmic localization of Hsp23 in CNS cells (PMID:32437379). Cytosol is an appropriate specific term. Supporting Evidence: PMID:32437379 The data show that sHSP23 and sHSP26 localize in the cytoplasm of CNS cells, in particular in the optic lobes and the central nerve cord file:DROME/Hsp23/Hsp23-deep-research-falcon.md sHsp23 is observed in **CNS cytoplasm** and to **concentrate at NMJ synaptic boutons** together with sHsp26 |
| GO:0006457 protein folding | ISM PMID:19715580 The small heat shock protein (sHSP) genes in the silkworm, B... | ACCEPT | Summary: ISM annotation for protein folding based on sequence model analysis. Li et al. (2009) performed comparative analysis of sHSP genes across insects, identifying conserved alpha-crystallin domains characteristic of chaperone function. Reason: The ISM evidence from comparative genomic analysis is consistent with experimental evidence (PMID:16572729) demonstrating chaperone activity. Supporting Evidence: PMID:19715580 sHSPs primarily have chaperone activity and reflect the response machine of organisms to some extreme stresses existing in environment |
| GO:0051082 unfolded protein binding | IDA PMID:16572729 Differences in the chaperone-like activities of the four mai... | MODIFY | Summary: Use the active holdase activity term for the demonstrated client-binding mechanism. Reason: Live QuickGO confirms that GO:0051082 is obsolete and GO:0140309 is active, named unfolded protein holdase activity. Its definition allows delivery to an acceptor molecule OR a specific location; it does not require transport between compartments. Full PMID:16572729 directly demonstrates client holding and later recovery by the reticulocyte chaperone machinery, with different efficiencies for each small Hsp. The active holdase term captures that activity; replacing the obsolete term with itself or awaiting a new term is unnecessary. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:16572729 Altogether, these results demonstrate that Hsp22, Hsp23, Hsp26, and Hsp27 can maintain heat-treated luciferase in a refoldable state, from which it can be refolded by other chaperones into an active enzyme. |
| GO:0051082 unfolded protein binding | ISM PMID:19715580 The small heat shock protein (sHSP) genes in the silkworm, B... | MODIFY | Summary: Use the active holdase activity term for the demonstrated client-binding mechanism. Reason: Live QuickGO confirms that GO:0051082 is obsolete and GO:0140309 is active, named unfolded protein holdase activity. Its definition allows delivery to an acceptor molecule OR a specific location; it does not require transport between compartments. Full PMID:16572729 directly demonstrates client holding and later recovery by the reticulocyte chaperone machinery, with different efficiencies for each small Hsp. The active holdase term captures that activity; replacing the obsolete term with itself or awaiting a new term is unnecessary. Proposed replacements: unfolded protein holdase activity Supporting Evidence: PMID:16572729 Altogether, these results demonstrate that Hsp22, Hsp23, Hsp26, and Hsp27 can maintain heat-treated luciferase in a refoldable state, from which it can be refolded by other chaperones into an active enzyme. |
| GO:0009408 response to heat | IDA PMID:26705243 Specific protein homeostatic functions of small heat-shock p... | ACCEPT | Summary: IDA annotation for response to heat from Vos et al. (2016). This study confirmed that the four classical sHSPs are all highly heat-inducible by qPCR in S2 cells. Reason: Strongly supported by experimental evidence. Hsp23 is one of the most abundantly constitutively expressed sHSPs and is highly heat-inducible (PMID:26705243). Supporting Evidence: PMID:26705243 The four classical small HSPs (HSP22, HSP23, HSP26, and HSP27) were all highly induced after a heat shock |
| GO:0042026 protein refolding | IDA PMID:26705243 Specific protein homeostatic functions of small heat-shock p... | ACCEPT | Summary: Hsp23 contributes to cellular protein refolding. Reason: Full PMID:26705243 directly reports improved luciferase recovery after Hsp23 overexpression in S2 cells. Hsp23 performs client protection, allowing later folding by cellular machinery. The HSP70-knockdown experiments in that paper were on Hsp27 and CG14207, so they do not specifically establish Hsp23 HSP70 dependence. Supporting Evidence: PMID:26705243 overexpression of the classical small HSPs (HSP23, HSP26, and HSP27) increased luciferase refolding |
| GO:0009631 cold acclimation | IEP PMID:16313561 Cold hardening and transcriptional change in Drosophila mela... | KEEP AS NON CORE | Summary: Hsp23 expression accompanies cold hardening. Reason: The source abstract explicitly identifies Hsp23 among the transcripts validated after cold-hardening treatment. Retain the curated expression-based response as contextual, while distinguishing induction from an individually demonstrated cold-protection mechanism. Full target assay details are unavailable; no claim that the curator is wrong or that an IEP annotation is inherently invalid. Supporting Evidence: PMID:16313561 Taken together, these assays suggest that stress proteins, including Hsp23, Hsp26, Hsp83 and Frost as well as membrane-associated proteins may contribute to the cold hardening response. |
| GO:0005515 protein binding | IPI PMID:9514881 Cloning and developmental expression of a nuclear ubiquitin-... | MODIFY | Summary: The verified Ubc9 association has a more informative binding term. Reason: PMID:9514881 explicitly reports Hsp23 interaction with DmUbc9 by two-hybrid and co-immunoprecipitation. Ubc9 is a SUMO-conjugating E2 enzyme, so GO:0044390 ubiquitin-like protein conjugating enzyme binding captures the partner class. This does not make Hsp23 a SUMO enzyme, nor does Ubc9 nuclear localization establish Hsp23 location. Proposed replacements: ubiquitin-like protein conjugating enzyme binding Supporting Evidence: PMID:9514881 Co-immunoprecipitation with antibody raised against DmUbc9 confirms the interaction with Drosophila Hsp23 |
| GO:0001666 response to hypoxia | IEP PMID:19401761 Distinct mechanisms underlying tolerance to intermittent and... | KEEP AS NON CORE | Summary: Hsp23 contributes to the constant-hypoxia response in the source model. Reason: Full PMID:19401761 measures Hsp23 induction by microarray/qPCR and higher survival of the Hsp23 P-element line under constant low oxygen (55% versus31% control), with increased Hsp23 mRNA. Excision reversal and tissue-specific overexpression in the paper concern Hsp70, so those stronger controls must not be reassigned to Hsp23. Retain the contextual response while the precise Hsp23 client-protection mechanism in hypoxia remains unspecified. Supporting Evidence: PMID:19401761 The survival rate was 55% for Hsp23 |
| GO:0001666 response to hypoxia | IMP PMID:19401761 Distinct mechanisms underlying tolerance to intermittent and... | KEEP AS NON CORE | Summary: Hsp23 contributes to the constant-hypoxia response in the source model. Reason: Full PMID:19401761 measures Hsp23 induction by microarray/qPCR and higher survival of the Hsp23 P-element line under constant low oxygen (55% versus31% control), with increased Hsp23 mRNA. Excision reversal and tissue-specific overexpression in the paper concern Hsp70, so those stronger controls must not be reassigned to Hsp23. Retain the contextual response while the precise Hsp23 client-protection mechanism in hypoxia remains unspecified. Supporting Evidence: PMID:19401761 The survival rate was 55% for Hsp23 |
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