hsp98 encodes the Neurospora crassa cytosolic Hsp100/ClpB-family disaggregase. The protein is a heat-shock Hsp104 ortholog predicted to form homohexameric AAA+ rings with central pores and, together with Hsp40, Hsp70, and small heat-shock proteins, to extract aggregated polypeptides by ATP-driven threading so they can refold. During heat shock, Neurospora Hsp98 is enriched in a microsomal fraction whose high-molecular-weight heat-shock proteins concentrate in polyribosomes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: Hsp98 is a ClpB/Hsp104-family protein with conserved AAA+ ATPase domains. Reason: The InterPro ATP-binding assertion is appropriate for this Hsp100/ClpB protein. The original Neurospora protein sequencing study found hsp98 sequence homology to E. coli ClpB and S. cerevisiae Hsp104, and the full UniProt sequence carries the same two AAA+ ATPase-domain architecture as fungal Hsp104 disaggregases. Supporting Evidence: PMID:1472534 This 28 amino acid sequence from hsp98 has 75% homology with a region of the ClpB protein of Escherichia coli and 86% homology to a 96-kDa protein of Trypanosoma brucei. It also has 71% homology to hsp104 of Saccharomyces cerevisiae. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | UNDECIDED | Summary: The nuclear localization row is a similarity-based UniProt mapping that was not directly verified in the cached Neurospora literature. Reason: S. cerevisiae HSP104 and S. pombe hsp104 both have nuclear pools during stress, so nuclear localization is plausible for N. crassa hsp98. The cached hsp98 primary paper is abstract-only and instead reports enrichment in a heat-shock microsomal fraction and polyribosomes, so it does not let this review verify the nuclear assertion. Supporting Evidence: PMID:1472534 Hsp98 was enriched in the microsomal fraction of heat-shocked cells. Sucrose gradient analysis of this cellular fraction showed that the three major high molecular weight heat-shock proteins (hsp98, 83 and 67) were more concentrated in polyribosomes than in monoribosomes. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: The broad cytoplasm IBA is consistent with hsp98 membership in the fungal cytosolic Hsp104 clade. Reason: Hsp98 is the N. crassa ortholog of fungal Hsp104, not a mitochondrial Hsp78 paralog. The broad PTHR11638 cytoplasm assertion is therefore appropriate, and the Neurospora primary study found hsp98 in a polyribosome-containing heat-shock fraction. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000181243 · PANTHER:PTN000181243 SUPPORTS TRANSFER Cytoplasm is placed at a broad Hsp100/ClpB node that includes the fungal cytosolic Hsp104 subtree containing Neurospora hsp98. Supporting Evidence: PMID:1472534 Hsp98 was enriched in the microsomal fraction of heat-shocked cells. Sucrose gradient analysis of this cellular fraction showed that the three major high molecular weight heat-shock proteins (hsp98, 83 and 67) were more concentrated in polyribosomes than in monoribosomes. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: The UniProt subcellular-location mapping is compatible with the PAINT cytoplasm inference and the direct hsp98 fractionation data. Reason: Hsp98 is a cytosolic Hsp104-family member. Although the original Neurospora paper localizes only fractionated heat-shock protein, its enrichment in polyribosome-containing fractions is consistent with a cytoplasmic protein. Supporting Evidence: PMID:1472534 Hsp98 was enriched in the microsomal fraction of heat-shocked cells. Sucrose gradient analysis of this cellular fraction showed that the three major high molecular weight heat-shock proteins (hsp98, 83 and 67) were more concentrated in polyribosomes than in monoribosomes. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: hsp98 lies in the fungal cytosolic Hsp104 subtree, so the cytosol placement is appropriate. Reason: PTN007521008 is the PAINT node for fungal Hsp104-like disaggregases, in contrast to the separate fungal mitochondrial Hsp78 node. Neurospora hsp98 clusters with Hsp104 rather than Hsp78 in the local PANTHER member table. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007521008 · PANTHER:PTN007521008 SUPPORTS TRANSFER Cytosol is placed on the fungal Hsp104 node from the S. cerevisiae seed, and Neurospora hsp98 descends from that node. Supporting Evidence: PMID:1472534 It also has 71% homology to hsp104 of Saccharomyces cerevisiae. |
| GO:0006457 protein folding | IEA GO_REF:0000117 | MODIFY | Summary: This broad ARBA chaperone process should be made specific to protein refolding. Reason: Hsp104/ClpB proteins do not generally fold nascent proteins; they disaggregate damaged proteins so they can be refolded. The fungal PAINT node already asserts GO:0042026 protein refolding for hsp98. Proposed replacements: protein refolding Supporting Evidence: PMID:1472534 Hsp98 is one of the most prominent proteins synthesized during the heat-shock response of Neurospora crassa. |
| GO:0016887 ATP hydrolysis activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATP hydrolysis is the conserved Hsp100/ClpB AAA+ activity. Reason: The PAINT transfer is appropriate: Neurospora hsp98 is a ClpB/Hsp104 homolog with conserved AAA+ ATPase domains and no evidence of catalytic loss. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000181243 · PANTHER:PTN000181243 SUPPORTS TRANSFER ATP hydrolysis is inherited from the broad Hsp100/ClpB ancestor and hsp98 retains the Hsp104-family ATPase domain architecture. Supporting Evidence: PMID:1472534 This 28 amino acid sequence from hsp98 has 75% homology with a region of the ClpB protein of Escherichia coli and 86% homology to a 96-kDa protein of Trypanosoma brucei. It also has 71% homology to hsp104 of Saccharomyces cerevisiae. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: The InterPro ATPase mapping agrees with the PANTHER IBA assertion. Reason: Hsp98 is a member of the ATP-dependent Hsp100/ClpB family, and this InterPro mapping captures the conserved AAA+ ATPase activity used by that family. Supporting Evidence: PMID:1472534 It also has 71% homology to hsp104 of Saccharomyces cerevisiae. |
| GO:0034605 cellular response to heat | IEA GO_REF:0000117 | ACCEPT | Summary: Heat response is correct for hsp98. Reason: Hsp98 is one of the major proteins synthesized during the N. crassa heat shock response, so the ARBA heat-response annotation is biologically appropriate. Supporting Evidence: PMID:1472534 Hsp98 is one of the most prominent proteins synthesized during the heat-shock response of Neurospora crassa. |
| GO:0042026 protein refolding | IBA GO_REF:0000033 | ACCEPT | Summary: Protein refolding is an appropriate inherited Hsp104-family process for Neurospora hsp98. Reason: hsp98 sits inside the fungal Hsp104 subtree that inherited aggregate reactivation and protein-refolding function. No Neurospora-specific loss or divergence is apparent from the sequence or literature. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007521008 · PANTHER:PTN007521008 SUPPORTS TRANSFER Protein refolding was placed at the fungal Hsp104 node from S. pombe support, and hsp98 is a descendant of that node. Supporting Evidence: PMID:1472534 It also has 71% homology to hsp104 of Saccharomyces cerevisiae. |
| GO:0043335 protein unfolding | IBA GO_REF:0000033 | ACCEPT | Summary: The Hsp104 disaggregase mechanism includes protein unfolding, and the fungal PAINT transfer is appropriate for hsp98. Reason: The fungal Hsp104 node contains proteins that extract and thread aggregated substrates through the AAA+ pore. Neurospora hsp98 retains this conserved Hsp104/ClpB architecture. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007521008 · PANTHER:PTN007521008 SUPPORTS TRANSFER Protein unfolding is placed at the fungal Hsp104 node from S. pombe and S. cerevisiae seed annotations. Supporting Evidence: PMID:1472534 This 28 amino acid sequence from hsp98 has 75% homology with a region of the ClpB protein of Escherichia coli and 86% homology to a 96-kDa protein of Trypanosoma brucei. It also has 71% homology to hsp104 of Saccharomyces cerevisiae. |
| GO:0043335 protein unfolding | IEA GO_REF:0000117 | ACCEPT | Summary: The ARBA protein-unfolding annotation agrees with the fungal Hsp104 PAINT annotation. Reason: Neurospora hsp98 is a cytosolic Hsp104-family AAA+ ATPase, so the inherited disaggregase mechanism that unfolds aggregated substrates is applicable. Supporting Evidence: PMID:1472534 It also has 71% homology to hsp104 of Saccharomyces cerevisiae. |
| GO:0051087 protein-folding chaperone binding | IBA GO_REF:0000033 | ACCEPT | Summary: The Hsp104 multichaperone pathway depends on partner chaperones, and this inherited row is plausible for hsp98. Reason: The protein-folding chaperone binding assertion is placed at the fungal Hsp104 node. hsp98 descends from that node and retains the sequence features of fungal cytosolic Hsp104 disaggregases. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007521008 · PANTHER:PTN007521008 SUPPORTS TRANSFER This molecular-function row is inherited from the fungal Hsp104 node seeded by S. cerevisiae HSP104. Supporting Evidence: PMID:1472534 It also has 71% homology to hsp104 of Saccharomyces cerevisiae. |
| GO:0070370 cellular heat acclimation | IBA GO_REF:0000033 | ACCEPT | Summary: Heat acclimation is appropriate for an Hsp104-family heat-shock disaggregase in Neurospora. Reason: The row is inherited from the fungal Hsp104 node. The Neurospora protein was isolated as a prominent heat-shock protein and no target-specific data argue against conservation of Hsp104-mediated thermotolerance. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007521008 · PANTHER:PTN007521008 SUPPORTS TRANSFER Cellular heat acclimation is placed at the fungal Hsp104 node using Candida, S. pombe, and S. cerevisiae experimental descendants; the short donor list is not weak support for hsp98. Supporting Evidence: PMID:1472534 Hsp98 is one of the most prominent proteins synthesized during the heat-shock response of Neurospora crassa. |
| GO:0140545 ATP-dependent protein disaggregase activity | ISS GO_REF:0000024 | NEW | Summary: Orthology to S. cerevisiae HSP104 supports the integrated ATP-dependent protein-disaggregase activity for Neurospora Hsp98. Reason: P31540 is the N. crassa ortholog of the fungal cytosolic Hsp104 disaggregase clade, and the N. crassa primary paper found direct peptide homology to S. cerevisiae Hsp104. ATP hydrolysis is a component subactivity, whereas GO:0140545 names the complete aggregate extraction and resolubilization activity performed by Hsp100/ClpB hexamers. Supporting Evidence: PMID:1472534 It also has 71% homology to hsp104 of Saccharomyces cerevisiae. |
Loading supporting content…
Download this section (compressed HTML)Q: Does Neurospora Hsp98 accumulate in the nucleus or in nuclear protein aggregate centers after heat shock, matching the nuclear pools described for S. cerevisiae and S. pombe Hsp104?
Experiment: Image endogenously tagged hsp98 before, during, and after acute heat shock to resolve whether the protein enters the nucleus or remains primarily cytosolic and ribosome-associated in N. crassa.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)