C. elegans HSP-90 (also known as DAF-21) is the sole cytosolic HSP90 homolog in nematodes. It functions as an ATP-dependent molecular chaperone that promotes the maturation, structural maintenance, and regulation of specific client proteins, particularly those involved in signal transduction (kinases, guanylyl cyclases) and steroid hormone receptor signaling. HSP-90 undergoes an ATP-dependent conformational cycle and works with co-chaperones including STI-1/Hop, CDC-37, AHA-1, and PPH-5. The protein is essential for larval development, chemosensory behavior, dauer formation, germline development, muscle maintenance, and organismal proteostasis. It is predominantly expressed in germline cells under normal conditions but is induced throughout the body under heat stress via the transcription factor PQM-1. HSP-90 plays a key role in transcellular chaperone signaling, where its expression in one tissue can protect against proteotoxic stress in distant tissues.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006457 protein folding | IBA GO_REF:0000033 | ACCEPT | Summary: HSP-90 is a core component of protein folding machinery in C. elegans. The IBA annotation is well-supported by extensive experimental evidence showing HSP-90's role in chaperoning client proteins including myosin, kinases, and signaling receptors (PMID:21980476, PMID:11809970, PMID:24012004). Reason: Protein folding is a core function of HSP-90 chaperones. Multiple experimental studies demonstrate that DAF-21/HSP-90 is required for proper folding of client proteins including myosin and signaling proteins (PMID:21980476, PMID:11809970). Supporting Evidence: PMID:21980476 Downregulation of the Hsp90 system causes defects in muscle cells of Caenorhabditis elegans PMID:11809970 UNC-45 functions both as a molecular chaperone and as an Hsp90 co-chaperone for myosin file:worm/hsp-90/hsp-90-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: HSP-90 ATPase activity is essential for its chaperone cycle. Direct experimental evidence from PMID:19559711 demonstrates that C. elegans HSP-90 has measurable ATPase activity that is regulated by co-chaperones such as STI-1/Hop. Reason: ATP hydrolysis is a defining feature of HSP90 family proteins that drives the conformational changes required for client protein processing. Direct experimental evidence demonstrates ATPase activity in CeHsp90 (PMID:19559711). Supporting Evidence: PMID:19559711 inhibition of the Hsp90 ATPase activity can be observed upon binding of CeHop PMID:20880838 Nematode Cdc37 binds with high affinity to Hsp90 and strongly inhibits the ATPase activity |
| GO:0032991 protein-containing complex | IBA GO_REF:0000033 | ACCEPT | Summary: HSP-90 forms multiple complexes with co-chaperones including CDC-37, STI-1/Hop, AHA-1, PPH-5, and UNC-45. This is documented in ComplexPortal entries and experimental studies (PMID:26593036, PMID:20880838, PMID:19559711). Reason: HSP-90 is documented to form multiple chaperone complexes (CPX-3983, CPX-3984, CPX-4002, CPX-4003, CPX-4004 in ComplexPortal). This is a core aspect of HSP90 function. Supporting Evidence: PMID:26593036 Hsp90 complexes are formed with two PPH-5 molecules PMID:20880838 Cdc37-Hsp90 complexes are responsive to nucleotide-induced conformational changes |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The IBA inference suggests some plasma membrane localization based on orthologs, but direct evidence for HSP-90 localization in C. elegans shows cytoplasmic localization with perinuclear enrichment rather than plasma membrane association. Reason: The experimental evidence in C. elegans (PMID:12950278, PMID:21980476) shows cytoplasmic localization with enrichment in the perinuclear region. A membrane raft HDA annotation (PMID:21070894) suggests some peripheral membrane association, but plasma membrane is not a primary or core location for the sole cytosolic HSP90. |
| GO:0005524 ATP binding | IBA GO_REF:0000033 | ACCEPT | Summary: ATP binding is essential for HSP-90 chaperone function. The UniProt entry documents multiple ATP binding sites (residues 39, 81, 100, 126, 371) with evidence from structural studies. ATP binding drives the conformational cycle. Reason: ATP binding is intrinsic to HSP90 function and is well-documented structurally in the UniProt record with specific binding residues identified. Supporting Evidence: PMID:19559711 The non-canonical Hop protein from Caenorhabditis elegans... Hsp90 ATPase activity |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Cytosolic localization is the primary location for HSP-90. This is supported by direct experimental evidence from IDA (PMID:12950278) showing cytoplasmic localization. Reason: Cytosolic localization is strongly supported by experimental evidence (IDA from PMID:12950278) and is consistent with HSP90 chaperone function. Supporting Evidence: PMID:12950278 the DAF-21 protein seemed to be localized in the perinuclear region of somatic cells |
| GO:0050821 protein stabilization | IBA GO_REF:0000033 | ACCEPT | Summary: HSP-90 stabilizes client proteins including signaling components. PMID:29949773 demonstrates that HSP-90 prevents protein misfolding and maintains proteostasis. PMID:10790386 shows HSP-90 stabilizes DAF-11 guanylyl cyclase. Reason: Protein stabilization is a core chaperone function. Experimental evidence from PMID:29949773 (IMP) directly supports this annotation. Supporting Evidence: PMID:29949773 mild perturbation of proteostasis in the neurons or the intestine activates TCS via the GATA zinc-finger transcription factor PQM-1 PMID:10790386 daf-21 encodes the heat-shock protein 90 (Hsp90), a chaperone with numerous specific protein targets |
| GO:0034605 cellular response to heat | IBA GO_REF:0000033 | ACCEPT | Summary: HSP-90 is induced by heat stress and plays a critical role in heat stress response. This is supported by IMP evidence from PMID:29949773 showing PQM-1-mediated induction of hsp-90 during heat stress. Reason: Cellular response to heat is well-documented for HSP-90 with direct experimental evidence (IMP from PMID:29949773). Supporting Evidence: PMID:29949773 hsp-90 expression in the control strain was dependent on hsf-1 or daf-16 PMID:12950278 Under heat stress conditions, however, daf-21 mRNA was not only detected in germ cells, but also apparently expressed all over the body |
| GO:0051082 unfolded protein binding | IBA GO_REF:0000033 | MODIFY | Summary: Binding unfolded proteins is a core molecular function of HSP90 chaperones. This is essential for the protein folding function and is well-supported by the conserved domain architecture. Reason: GO:0051082 is now formally obsolete. HSP-90 is an ATP-dependent foldase chaperone. The appropriate replacement term is GO:0044183 (protein folding chaperone). Proposed replacements: protein folding chaperone Supporting Evidence: PMID:24012004 EBAX-1 specifically recognizes misfolded SAX-3 and promotes its degradation |
| GO:0048471 perinuclear region of cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Perinuclear localization is directly demonstrated by experimental evidence from PMID:12950278, which shows DAF-21 protein localization to the perinuclear region of somatic cells. Reason: This is supported by direct experimental evidence (IDA from PMID:12950278) showing perinuclear localization. Supporting Evidence: PMID:12950278 the DAF-21 protein seemed to be localized in the perinuclear region of somatic cells |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: Nucleotide binding is a more general term than ATP binding. Given that ATP binding (GO:0005524) is already annotated with IBA evidence, this IEA annotation is redundant but not incorrect. Reason: This is a correct but less specific annotation compared to ATP binding. It reflects the known ATP-binding properties of HSP90. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of the IBA annotation for ATP binding. Both annotations are correct. Reason: ATP binding is well-supported by structural and functional evidence. This IEA annotation is consistent with the IBA annotation. |
| GO:0006457 protein folding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro domain-based annotation consistent with the IBA and IDA annotations for protein folding. Reason: Protein folding annotation based on HSP90 domain (IPR001404) is correct and consistent with experimental evidence. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro domain-based annotation consistent with the IBA and IDA annotations for ATP hydrolysis. Reason: ATP hydrolysis is a defining feature of HSP90 proteins and is correctly inferred from domain architecture. |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: This IEA annotation duplicates the IBA and IDA annotations for perinuclear localization. Reason: Consistent with experimental evidence from PMID:12950278. |
| GO:0051082 unfolded protein binding | IEA GO_REF:0000002 | MODIFY | Summary: GO:0051082 is now formally obsolete. InterPro domain-based annotation consistent with the IBA annotation. Reason: GO:0051082 is now formally obsolete. HSP-90 is an ATP-dependent foldase chaperone. The appropriate replacement term is GO:0044183 (protein folding chaperone). Consistent with MODIFY on IBA annotation. Proposed replacements: protein folding chaperone |
| GO:0101031 protein folding chaperone complex | IEA GO_REF:0000117 | ACCEPT | Summary: HSP-90 is a component of multiple chaperone complexes documented in ComplexPortal (CPX-3983, CPX-3984, CPX-4002, CPX-4003, CPX-4004). Reason: HSP-90 is well-documented as forming chaperone complexes with co-chaperones. |
| GO:0140662 ATP-dependent protein folding chaperone | IEA GO_REF:0000002 | ACCEPT | Summary: This is the most specific molecular function term for HSP90 chaperone activity, correctly capturing both the ATP-dependence and protein folding chaperone function. Reason: This accurately describes the core molecular function of HSP-90 as an ATP-dependent chaperone. |
| GO:0005515 protein binding | IPI PMID:11809970 Role of the myosin assembly protein UNC-45 as a molecular ch... | MODIFY | Summary: This IPI annotation reports HSP-90 binding to UNC-45 (G5EG62). PMID:11809970 demonstrates that UNC-45 functions as an HSP90 co-chaperone for myosin, with the TPR domain of UNC-45 binding HSP90. Reason: The interaction with UNC-45 is biologically meaningful as UNC-45 is an HSP90 co-chaperone. However, "protein binding" is too vague. A more specific term should be used. Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:11809970 Role of the myosin assembly protein UNC-45 as a molecular chaperone for myosin. |
| GO:0005515 protein binding | IPI PMID:14992718 Systematic interactome mapping and genetic perturbation anal... | MODIFY | Summary: This IPI annotation reports HSP-90 binding to DAF-1 (P20792), a TGF-beta receptor. The study used systematic yeast two-hybrid mapping of the TGF-beta signaling network. Reason: The interaction with DAF-1 is relevant as HSP90 chaperones signaling receptors. However, "protein binding" is uninformative. Consider a more specific term. Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:14992718 Systematic interactome mapping and genetic perturbation analysis of a C. |
| GO:0005515 protein binding | IPI PMID:16672054 Direct and heterologous approaches to identify the LET-756/F... | MODIFY | Summary: This IPI annotation reports HSP-90 binding to LET-756/FGF (Q11184). The study identified DAF-21 as an interactor of the FGF homolog in yeast two-hybrid screens. Reason: While the interaction is documented, "protein binding" is too general. HSP90 likely acts as a chaperone for signaling proteins like FGFs. Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:16672054 DAF-21, a chaperone of the HSP-90 family, involved in chemosensory transduction and insulin signalization |
| GO:0005515 protein binding | IPI PMID:19467242 C. elegans STI-1, the homolog of Sti1/Hop, is involved in ag... | MODIFY | Summary: This IPI annotation reports HSP-90 binding to STI-1 (O16259). STI-1/Hop is a well-established HSP90 co-chaperone that bridges HSP70 and HSP90. Reason: This is a functionally significant interaction with a bona fide co-chaperone. A more specific term should be used. Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:19467242 CeSTI-1 can bind with both Hsp70 and Hsp90 homologs like its mammalian counterpart |
| GO:0005515 protein binding | IPI PMID:19559711 The non-canonical Hop protein from Caenorhabditis elegans ex... | MODIFY | Summary: This IPI annotation reports HSP-90 binding to STI-1 (O16259). The study demonstrates binary complex formation between CeHop and either Hsc70 or Hsp90. Reason: Duplicate of the interaction reported in PMID:19467242. The interaction is validated but "protein binding" should be replaced with a more informative term. Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:19559711 physical interactions with both chaperones Hsp70 and Hsp90, albeit only the interaction with Hsp90 is strong |
| GO:0005515 protein binding | IPI PMID:23332754 The myosin chaperone UNC-45 is organized in tandem modules t... | MODIFY | Summary: This IPI annotation reports HSP-90 binding to UNC-45 (G5EG62). The study examines UNC-45 organization in tandem modules for myofilament formation. Reason: Duplicate of the UNC-45 interaction reported in PMID:11809970. A more specific term should be used. Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:23332754 The myosin chaperone UNC-45 is organized in tandem modules to support myofilament formation in C. |
| GO:0005515 protein binding | IPI PMID:23746847 Regulation of organismal proteostasis by transcellular chape... | MODIFY | Summary: This IPI annotation reports HSP-90 binding to MYO-3/myosin (P02566). The study demonstrates transcellular chaperone signaling where HSP-90 protects against muscle protein misfolding. Reason: This represents HSP-90 chaperoning of a client protein (myosin). A more specific term reflecting chaperone-client interaction would be more informative. Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:23746847 expression of endogenous metastable proteins in muscle cells, which rely on chaperones for proper folding |
| GO:0042802 identical protein binding | IPI PMID:14992718 Systematic interactome mapping and genetic perturbation anal... | ACCEPT | Summary: HSP-90 forms homodimers as a core aspect of its function. This is well-documented in PMID:26593036 and is essential for the chaperone cycle. Reason: HSP90 homodimerization is a core feature required for chaperone function. This annotation is accurate and informative. Supporting Evidence: PMID:26593036 Hsp90 complexes are formed with two PPH-5 molecules PMID:14992718 Systematic interactome mapping and genetic perturbation analysis of a C. |
| GO:0051604 protein maturation | NAS PMID:20880838 Cdc37-Hsp90 complexes are responsive to nucleotide-induced c... | ACCEPT | Summary: PMID:20880838 discusses Cdc37-Hsp90 complexes and their role in kinase client processing. HSP90 is known to facilitate maturation of signaling proteins. Reason: Protein maturation is a well-established function of HSP90 chaperone complexes, particularly for kinase clients via the Cdc37 co-chaperone pathway. Supporting Evidence: PMID:20880838 Many client proteins are protein kinases, which are activated and stabilized by Hsp90 in cooperation with the kinase-specific co-chaperone Cdc37 |
| GO:0006457 protein folding | IDA PMID:21980476 Downregulation of the Hsp90 system causes defects in muscle ... | ACCEPT | Summary: PMID:21980476 provides direct experimental evidence that downregulation of HSP-90 causes protein folding defects in muscle cells, with visible aggregation of MYO-3 myosin. Reason: Direct experimental evidence from PMID:21980476 demonstrates that HSP-90 is required for proper folding of muscle proteins. Supporting Evidence: PMID:21980476 aggregates of the myosin MYO-3 are visible in muscle cells, if DAF-21 is depleted, implying a role of Hsp90 in the maintenance of muscle cell functionality |
| GO:0072542 protein phosphatase activator activity | IDA PMID:26593036 The activity of protein phosphatase 5 towards native clients... | ACCEPT | Summary: PMID:26593036 demonstrates that HSP-90 interaction with PPH-5 (protein phosphatase 5) stimulates the phosphatase activity. This is a specific molecular function annotation. Reason: Direct experimental evidence shows that HSP-90 activates PPH-5 phosphatase activity through direct interaction. Supporting Evidence: PMID:26593036 The activity of protein phosphatase 5 towards native clients is modulated by the middle- and C-terminal domains of Hsp90 |
| GO:0009408 response to heat | IGI PMID:16916933 Heat-shock transcription factor (HSF)-1 pathway required for... | ACCEPT | Summary: PMID:16916933 demonstrates that HSF-1 pathway, including HSP-90, is required for heat stress response and immunity. The IGI evidence involves HSF-1. Reason: Response to heat is a core function of heat shock proteins. This is supported by multiple experimental studies. Supporting Evidence: PMID:16916933 The HSF-1 defense response... requires a system of chaperones including small and 90-kDa inducible HS proteins |
| GO:0050829 defense response to Gram-negative bacterium | IGI PMID:16916933 Heat-shock transcription factor (HSF)-1 pathway required for... | KEEP AS NON CORE | Summary: PMID:16916933 shows that HSF-1 and its downstream chaperones including HSP-90 are required for C. elegans immunity against Gram-negative bacteria like P. aeruginosa. Reason: While HSP-90 participates in immunity through the HSF-1 pathway, this represents a downstream consequence of its chaperone function rather than a core molecular activity. The primary role of HSP-90 is protein folding/maturation. Supporting Evidence: PMID:16916933 HSF-1 is required for C. elegans immunity against Pseudomonas aeruginosa, Salmonella enterica, Yersinia pestis, and Enterococcus faecalis |
| GO:0034605 cellular response to heat | IMP PMID:29949773 A PQM-1-Mediated Response Triggers Transcellular Chaperone S... | ACCEPT | Summary: PMID:29949773 provides direct mutant phenotype evidence showing that HSP-90 is induced by heat stress and is required for transcellular chaperone signaling and proteostasis. Reason: Direct experimental evidence from mutant analysis demonstrates HSP-90's role in cellular response to heat. Supporting Evidence: PMID:29949773 PQM-1 Regulates Heat-Inducible Expression of hsp-90 and Is Involved in Proteostasis |
| GO:0050821 protein stabilization | IMP PMID:29949773 A PQM-1-Mediated Response Triggers Transcellular Chaperone S... | ACCEPT | Summary: PMID:29949773 demonstrates that HSP-90 prevents protein misfolding and stabilizes proteins under stress conditions through transcellular chaperone signaling. Reason: Direct experimental evidence shows HSP-90's role in maintaining protein stability and preventing misfolding. Supporting Evidence: PMID:29949773 mild perturbation of proteostasis in the neurons or the intestine activates TCS |
| GO:0032991 protein-containing complex | IPI PMID:26593036 The activity of protein phosphatase 5 towards native clients... | ACCEPT | Summary: PMID:26593036 demonstrates HSP-90 complex formation with PPH-5 and glucocorticoid receptor through physical interaction experiments. Reason: Complex formation is well-documented experimentally and is essential for HSP-90 chaperone function. Supporting Evidence: PMID:26593036 Hsp90-protein phosphatase 5 complexes |
| GO:1990634 protein phosphatase 5 binding | IPI PMID:26593036 The activity of protein phosphatase 5 towards native clients... | ACCEPT | Summary: PMID:26593036 directly demonstrates binding between HSP-90 and PPH-5 (protein phosphatase 5 ortholog) using biochemical assays. Reason: This is a specific and informative molecular function annotation with direct experimental evidence. Supporting Evidence: PMID:26593036 CeHsp90 regulates PPH-5 also from outside the TPR-region |
| GO:0032991 protein-containing complex | IDA PMID:26593036 The activity of protein phosphatase 5 towards native clients... | ACCEPT | Summary: Duplicate of the IPI annotation from the same reference. Both support HSP-90 complex formation. Reason: Consistent with the IPI annotation and multiple ComplexPortal entries. Supporting Evidence: PMID:26593036 The activity of protein phosphatase 5 towards native clients is modulated by the middle- and C-terminal domains of Hsp90. |
| GO:0035259 nuclear glucocorticoid receptor binding | IPI PMID:26593036 The activity of protein phosphatase 5 towards native clients... | KEEP AS NON CORE | Summary: PMID:26593036 shows C. elegans HSP-90 binding the ligand-binding domain of the human glucocorticoid receptor (P04150) in vitro, and forming ternary HSP-90/PPH-5/GR complexes. Reason: The interaction is directly demonstrated, but with a heterologous mammalian client used as a mechanistic probe; C. elegans has no glucocorticoid receptor ortholog as a native client. It reflects conserved steroid-receptor chaperoning biochemistry rather than a core native function, so keep as non-core. Supporting Evidence: PMID:26593036 ternary complexes with the glucocorticoid receptor (GR) are cooperatively formed |
| GO:0006611 protein export from nucleus | IMP PMID:23396260 Yes-associated protein homolog, YAP-1, is involved in the th... | KEEP AS NON CORE | Summary: PMID:23396260 shows that DAF-21/HSP-90 is required for nuclear export of YAP-1 after heat shock treatment. Knockdown of DAF-21 blocks YAP-1 nuclear export during heat shock recovery. Reason: While HSP-90 regulates YAP-1 nuclear export, this is likely a consequence of its general chaperone function rather than a direct nuclear export activity. HSP-90 may chaperone components of the nuclear export machinery. Supporting Evidence: PMID:23396260 Knockdowns of DAF-21 (HSP90 ortholog) and HSF-1block the nuclear export of YAP-1 during this recovery |
| GO:0006935 chemotaxis | IGI PMID:7828815 Multiple chemosensory defects in daf-11 and daf-21 mutants o... | KEEP AS NON CORE | Summary: PMID:7828815 demonstrates that daf-21 mutants have defects in chemotaxis to volatile and non-volatile attractants detected by specific amphid neurons. Reason: Chemotaxis defects in daf-21 mutants are indirect consequences of HSP-90's role in stabilizing signaling components (e.g., DAF-11 guanylyl cyclase) rather than direct involvement in chemotaxis per se. Supporting Evidence: PMID:7828815 daf-11 and daf-21 mutants are not defective in avoidance of certain non-volatile repellents, but are defective in taxis to non-volatile attractants |
| GO:0050920 regulation of chemotaxis | IMP PMID:7828815 Multiple chemosensory defects in daf-11 and daf-21 mutants o... | KEEP AS NON CORE | Summary: The same study (PMID:7828815) shows that daf-21 regulates chemotaxis through its role in cGMP signaling pathway. Reason: While HSP-90 affects chemotaxis, this is an indirect effect through stabilization of signaling components like DAF-11 guanylyl cyclase, not a core molecular function. Supporting Evidence: PMID:7828815 We propose that daf-11 and daf-21 mediate sensory transduction for both volatile and non-volatile compounds in specific amphid neurons |
| GO:0005515 protein binding | IPI PMID:17610845 Cloning, expression and characterisation of FKB-6, the sole ... | MODIFY | Summary: PMID:17610845 demonstrates binding between HSP-90's C-terminal MEEVD motif and FKB-6 (O45418), a TPR-containing immunophilin co-chaperone. Reason: This is a functionally relevant co-chaperone interaction. A more specific term should be used instead of generic "protein binding." Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:17610845 NMR studies of the interaction between FKB-6 and the C-terminal DAF-21 pentapeptide MEEVD show interactions consistent with those found between the large human immunophilin TPR domains and human Hsp90 |
| GO:0005515 protein binding | IPI PMID:24012004 The EBAX-type Cullin-RING E3 ligase and Hsp90 guard the prot... | MODIFY | Summary: PMID:24012004 demonstrates that DAF-21/HSP-90 binds to EBAX-1 (Q21875) and collaboratively regulates SAX-3/Robo receptor quality control in neurons. Reason: This is a functionally significant interaction in protein quality control. A more specific term would be more informative. Proposed replacements: Hsp90 protein binding Supporting Evidence: PMID:24012004 EBAX-1 also binds to DAF-21, a cytosolic Hsp90 chaperone. The EBAX-type CRL and DAF-21 collaboratively regulate SAX-3-mediated axon pathfinding |
| GO:0045121 membrane raft | HDA PMID:21070894 An analysis of the Caenorhabditis elegans lipid raft proteom... | KEEP AS NON CORE | Summary: HDA annotation from a geLC-MS/MS survey of the C. elegans lipid raft fraction. The cached record is abstract-only and does not name individual proteins; the identification of HSP-90 rests on the GOA curator's reading of the full text, which is deferred to. Reason: The annotation is accepted as made by the curator, but detection in a detergent-resistant membrane fraction by mass spectrometry does not make membrane rafts a core location of a predominantly cytosolic/perinuclear chaperone (PMID:12950278, PMID:21980476). Keep as non-core. |
| GO:0016887 ATP hydrolysis activity | IDA PMID:19559711 The non-canonical Hop protein from Caenorhabditis elegans ex... | ACCEPT | Summary: PMID:19559711 provides direct experimental measurement of C. elegans HSP-90 ATPase activity and its regulation by co-chaperones. Reason: Direct experimental demonstration of ATPase activity with measurements of activity modulation by co-chaperones. Supporting Evidence: PMID:19559711 inhibition of the Hsp90 ATPase activity can be observed upon binding of CeHop |
| GO:0002119 nematode larval development | IMP PMID:10790386 A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21)... | KEEP AS NON CORE | Summary: PMID:10790386 demonstrates that daf-21 mutants have larval development defects, with daf-21 null being early larval lethal. Reason: While HSP-90 is essential for larval development, this is a pleiotropic phenotypic outcome of its general chaperone function rather than a core molecular activity. Supporting Evidence: PMID:10790386 the daf-21 null phenotype is early larval lethality |
| GO:0008340 determination of adult lifespan | IGI PMID:14668486 Regulation of longevity in Caenorhabditis elegans by heat sh... | KEEP AS NON CORE | Summary: PMID:14668486 shows that HSF-1 and molecular chaperones including HSP-90 regulate longevity in C. elegans, interacting with the insulin-like signaling pathway. Reason: While HSP-90 affects lifespan through its role in proteostasis and stress response, this is a downstream phenotypic consequence rather than a direct molecular function. Supporting Evidence: PMID:14668486 Down-regulation of individual molecular chaperones, transcriptional targets of HSF-1, also decreased longevity of long-lived mutant but not wild-type animals |
| GO:0005737 cytoplasm | IDA PMID:12950278 Caenorhabditis elegans DAF-21 (HSP90) is characteristically ... | ACCEPT | Summary: PMID:12950278 provides direct immunofluorescence evidence for cytoplasmic localization of DAF-21 protein. Reason: Direct experimental evidence for cytoplasmic localization from antibody staining and in situ hybridization. Supporting Evidence: PMID:12950278 the DAF-21 protein seemed to be localized in the perinuclear region of somatic cells |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:12950278 Caenorhabditis elegans DAF-21 (HSP90) is characteristically ... | ACCEPT | Summary: PMID:12950278 demonstrates perinuclear localization of DAF-21 in somatic cells using monoclonal antibodies. Reason: Direct experimental evidence from antibody staining shows perinuclear localization. Supporting Evidence: PMID:12950278 the DAF-21 protein seemed to be localized in the perinuclear region of somatic cells |
| GO:0040024 dauer larval development | IMP PMID:11677050 DAF-7/TGF-beta expression required for the normal larval dev... | KEEP AS NON CORE | Summary: PMID:11677050 demonstrates that daf-21 acts upstream of daf-7/TGF-beta in dauer formation, regulating the developmental switch. Reason: Dauer larval development is a developmental process affected by HSP-90's role in chaperoning signaling components (DAF-11), not a direct molecular function. Supporting Evidence: PMID:11677050 daf-11 gene and a related gene daf-21 act upstream of daf-7 |
| GO:0040024 dauer larval development | IGI PMID:11677050 DAF-7/TGF-beta expression required for the normal larval dev... | KEEP AS NON CORE | Summary: Duplicate annotation with IGI evidence from the same reference, involving genetic interaction with daf-11. Reason: Same reasoning as the IMP annotation - dauer development is a downstream phenotype of HSP-90's chaperone function in signaling pathways. Supporting Evidence: PMID:11677050 DAF-7/TGF-beta expression required for the normal larval development in C. |
| GO:0044183 protein folding chaperone | NAS | NEW | Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. |
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Download this section (compressed HTML)Q: What are the specific client proteins chaperoned by HSP-90/DAF-21 in different C. elegans tissues, and how do co-chaperone preferences vary by tissue?
Q: How does the transcellular chaperone signaling mechanism work mechanistically? What signals are transmitted between tissues to coordinate HSP-90 expression?
Experiment: Identify tissue-specific HSP-90 client proteins using proximity labeling approaches (e.g., TurboID) in different C. elegans tissues.
Hypothesis: HSP-90 interacts with multiple signal transduction proteins beyond DAF-11
Experiment: Characterize the molecular signals transmitted during transcellular chaperone signaling using metabolomics and secretome analysis.
Experiment: Determine tissue-specific requirements for HSP-90 using tissue-specific RNAi, to clarify which tissues require it for viability and for specific developmental phenotypes.
Hypothesis: HSP-90 is required in multiple tissues for different aspects of development
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