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. In oocytes it is needed for normal levels of the CDK-1 inhibitory kinase WEE-1.3 and so for diakinesis arrest at the meiotic prophase/metaphase boundary; daf-21(RNAi) oocytes become endomitotic, like wee-1.3(RNAi) oocytes. 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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