HSP17.6A (AtHsp17.6A-CI; locus At1g59860; UniProt Q9XIE3) is a 17.6 kDa class I cytosolic small heat shock protein (sHSP) of the HSP20/alpha-crystallin family. Like other sHSPs it is defined by a conserved alpha-crystallin domain (ACD) flanked by a variable N-terminal region and short C-terminal extension, and it functions as an ATP-independent holdase chaperone: it binds non-native (unfolding/denaturing) client proteins to prevent their irreversible aggregation and keeps them soluble and refoldable, with actual refolding delegated to downstream ATP-dependent systems (e.g. HSP70/HSP100). It is not an enzyme or transporter; its functional "substrate" is misfolded protein. sHSPs form large dynamic oligomers, and oligomerization is integral to the chaperone mechanism. HSP17.6A is a canonical heat shock response gene under strong positive control by the HsfA1 transcription factor regulon (perfect HSE in its promoter) and is additionally modulated by miR160/ARF circuitry; its expression is induced by heat, osmotic and salt stress, and overexpression enhances osmotolerance (PMID:11576425). It is annotated as cytosol/nucleus (c/n). Single-gene loss-of-function phenotypes are expected to be subtle because Arabidopsis has multiple highly similar cytosolic class I sHSP paralogs (e.g. AtHsp17.6B-CI, AtHsp17.6C-CI), which complicates assigning unique in vivo functions and means much functional evidence is paralog-shared.
Definition: Binding to an unfolded or misfolded protein to prevent its aggregation without actively catalyzing refolding. The holdase maintains the client protein in a soluble, folding-competent state.
Justification: HSP17.6A: HSP17.6A is an ATP-independent holdase chaperone (class I cytosolic sHSP) that binds non-native/unfolding client proteins to prevent their irreversible aggregation, keeping them soluble and refoldable for downstream ATP-dependent chaperones (HSP70/HSP100). Obsolete GO:0051082 captured binding only; GO:0044183 requires assisting folding, and GO:0140309 (relabelled 'unfolded protein holdase activity') keeps a carrier-specific definition requiring escort to an acceptor molecule or location, which is not demonstrated here. See go-ontology#30552. Gene-identity caveat: PMID:11576425 names its gene At-HSP17.6A but describes it as the cytosolic class II sHSP, whereas Q9XIE3/At1g59860 is class I (the class II gene is HSP17.7/At5g12030); UniProt nonetheless cites the paper for Q9XIE3, so the class-I holdase assertion here rests jointly on that citation and on family-level sHSP evidence.
Parent term: molecular_function
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0009408 response to heat | IBA GO_REF:0000033 | ACCEPT | Summary: HSP17.6A is a class I cytosolic sHSP that is transcriptionally induced by heat and is a canonical heat shock response gene. Falcon deep research corroborates strong HsfA1-dependent heat induction (perfect HSE in its promoter), consistent with this IBA annotation across the HSP20 family. Response to heat is a defining biological process for sHSPs. Reason: Heat shock response is a defining characteristic of sHSPs and is supported by phylogenetic inference (IBA), by direct heat-inducible expression (PMID:11576425), and by falcon evidence that HSP17.6A is under strong positive HsfA1 control. Supporting Evidence: file:ARATH/HSP17.6A/HSP17.6A-deep-research-falcon.md These observations support that **HSP17.6A is a canonical heat shock response gene** under strong positive control by HsfA1 family activity. |
| GO:0051082 unfolded protein binding | IBA GO_REF:0000033 | MODIFY | Summary: GO:0051082 (unfolded protein binding) is now formally obsolete (go-ontology#30962). HSP17.6A is a classic ATP-independent sHSP holdase that binds non-native/unfolding proteins to prevent aggregation but does not actively refold them. Per UPB project decision rules, sHSPs should be reannotated to a holdase chaperone activity NTR when created. GO:0140309 (unfolded protein carrier activity) does not fit because it is carrier-specific (created for TIM chaperones per go-ontology#30552), whereas sHSPs are in-situ holdases. GO:0044183 (protein folding chaperone) does not fit because sHSPs do not catalyze folding. This is the core molecular function. Reason: sHSPs like HSP17.6A are ATP-independent holdases: they bind denaturing proteins to prevent aggregation in situ but do not actively refold them. GO:0044183 is inappropriate (no active folding) and GO:0140309 is carrier-specific (go-ontology#30552). A general holdase chaperone activity NTR is needed. Propagation Review Root cause: SOURCE STALE OR MISSING Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000163021 · plant/fungal sHSP node SOURCE STALE OR MISSING The current PTHR11527 PAINT slice carries protein folding (GO:0006457), response-to-heat and oligomerization IBDs at this node but no GO:0051082; the unfolded-protein-binding IBD appears to have been withdrawn upstream. PomBase:SPBC3E7.02c · fission-yeast small heat shock protein SUPPORTS TRANSFER sHSP holdase-type client binding is real; the open issue is the lack of a GO term for ATP-independent holdase activity, tracked in the review reason. Proposed replacements: holdase chaperone activity Supporting Evidence: file:ARATH/HSP17.6A/HSP17.6A-deep-research-falcon.md They bind **non-native (unfolded or partially unfolded) client proteins** in an **ATP-independent** manner, keeping clients soluble so that other ATP-dependent systems (e.g., HSP70/HSP100) can later refold them. Because they do not actively refold proteins themselves, sHSPs are described as **“holdases.”** file:ARATH/HSP17.6A/HSP17.6A-deep-research-falcon.md ATP-independent molecular chaperone/holdase contributing to proteostasis under conditions that increase protein misfolding (especially heat stress). |
| GO:0006457 protein folding | IBA GO_REF:0000033 | ACCEPT | Summary: The IBA annotation to GO:0006457 (protein folding) is phylogenetically inferred for the HSP20 family. sHSPs participate in the broader protein folding/quality-control pathway by binding unfolding proteins and preventing aggregation, holding substrates folding-competent for downstream ATP-dependent chaperones, but they do not themselves catalyze folding. Falcon corroborates the family-level holdase mechanism. The involved_in/process-level annotation is acceptable. Reason: While sHSPs do not actively fold proteins, they participate in the protein folding process at the BP level by preventing irreversible aggregation and maintaining substrates for refolding by HSP70-type foldases. The IBA inference is phylogenetically sound for the HSP20 family. Supporting Evidence: file:ARATH/HSP17.6A/HSP17.6A-deep-research-falcon.md HSP17.6A most plausibly contributes to **proteostasis** by binding unfolding proteins and preventing aggregation during stress, acting upstream of ATP-dependent refolding systems. |
| GO:0009651 response to salt stress | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Manual review: response to salt stress may be context-dependent or peripheral for HSP17.6A. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0042542 response to hydrogen peroxide | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Manual review: response to hydrogen peroxide may be context-dependent or peripheral for HSP17.6A. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0051259 protein complex oligomerization | IBA GO_REF:0000033 | ACCEPT | Summary: sHSPs characteristically form large, dynamic oligomeric complexes that dissociate and reassociate in response to stress; substrate binding is coupled to this dynamic oligomerization. UniProt notes HSP17.6A forms oligomeric structures, and falcon corroborates the family-level dynamic oligomerization mechanism. The IBA annotation is well supported across the sHSP family. Reason: Oligomerization is a core structural and functional property of sHSPs, integral to the holdase chaperone mechanism rather than a peripheral function. The IBA annotation is phylogenetically sound and consistent with UniProt. Supporting Evidence: file:ARATH/HSP17.6A/HSP17.6A-deep-research-falcon.md ACD-type sHSPs form large oligomers (reported in the review as commonly **~150–800 kDa**), and these oligomers are **dynamic** and can rearrange with temperature or other conditions. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization is inferred from UniProt subcellular location. HSP17.6A is a class I cytosolic sHSP, and falcon corroborates a curated cytosol/nucleus (c/n) annotation. The cytoplasm term is consistent with the cytosolic site of action; the protein may also partition to the nucleus during heat stress. Reason: Cytoplasmic localization is well established for this cytosolic class I sHSP and is consistent with the UniProt subcellular annotation and the curated c/n annotation surfaced by falcon. Supporting Evidence: file:ARATH/HSP17.6A/HSP17.6A-deep-research-falcon.md AtHsp17.6A-CI (Q9XIE3) is annotated as **c/n** in a curated sHSP overview table, consistent with cytosolic class I sHSP behavior in plants. |
| GO:0006950 response to stress | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Manual review: response to stress may be context-dependent or peripheral for HSP17.6A. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0071456 cellular response to hypoxia | HEP PMID:31519798 Integrative Analysis from the Epigenome to Translatome Uncov... | KEEP AS NON CORE | Summary: Manual review: cellular response to hypoxia may be context-dependent or peripheral for HSP17.6A. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. |
| GO:0005737 cytoplasm | ISM GO_REF:0000122 | ACCEPT | Summary: Manual review: cytoplasm is consistent with known biology of HSP17.6A. Reason: Retained as supported or plausible for this gene and evidence context. |
| GO:0005515 protein binding | IPI PMID:21730198 Small heat shock protein Hsp17.8 functions as an AKR2A cofac... | MARK AS OVER ANNOTATED | Summary: GO:0005515 (protein binding) is uninformative and does not capture the biology of HSP17.6A. The IPI derives from PMID:21730198, a study focused on the paralog Hsp17.8 as an AKR2A cofactor that notes "Other CI cytosolic sHsps also interact with AKR2A to varying degrees" -- i.e. the interaction is paralog-shared rather than HSP17.6A-specific. The informative molecular function for HSP17.6A is its ATP-independent holdase / unfolded protein binding activity, which core_functions records as the proposed holdase chaperone activity. Falcon emphasizes that the multiplicity of highly similar cytosolic sHSP paralogs makes single-gene assignments uncertain, reinforcing that this generic binding term should not be elevated. Reason: 'protein binding' is too generic to be informative, and the underlying AKR2A interaction is paralog-shared (the primary study is on Hsp17.8). The biologically informative MF (unfolded protein binding / holdase activity) is represented elsewhere in this review and in core_functions. Supporting Evidence: file:ARATH/HSP17.6A/HSP17.6A-deep-research-falcon.md plants’ multiplicity of highly similar sHSPs in the same compartment makes it challenging to define the in vivo relevance of each single paralog |
| GO:0006457 protein folding | IDA PMID:11576425 At-HSP17.6A, encoding a small heat-shock protein in Arabidop... | ACCEPT | Summary: The IDA annotation is based on the in vitro chaperone activity demonstrated in PMID:11576425. The sHSP mechanism is holdase-type (prevents aggregation of denaturing substrates without active refolding), so participation in the protein folding process is at the BP/pathway level upstream of HSP70-type foldases. (Note: this paper characterizes a "cytosolic class II smHSP" called At-HSP17.6A; UniProt Q9XIE3 cites it for FUNCTION and OLIGOMERIZATION, so the curated annotation is retained here, but there is nomenclature ambiguity with the class II paralog HSP17.7/O81822.) Reason: sHSPs participate in the protein quality-control/folding pathway by preventing aggregation and maintaining substrates for subsequent refolding. The in vitro chaperone assay in PMID:11576425 demonstrated this activity; involvement at the BP level is accurate. Supporting Evidence: PMID:11576425 The chaperone activity of At-HSP17.6A was demonstrated in vitro. |
| GO:0006970 response to osmotic stress | IEP PMID:11576425 At-HSP17.6A, encoding a small heat-shock protein in Arabidop... | KEEP AS NON CORE | Summary: The IEP annotation reflects that expression is induced by osmotic stress (PMID:11576425) and that overexpression enhances osmotolerance. This is a stress-protective phenotype mediated by the holdase chaperone activity rather than a core molecular function. Falcon corroborates the osmotolerance-upon-overexpression claim (secondary-cited). Reason: Osmotic stress response is a downstream phenotypic consequence of the general proteostasis/ holdase function rather than a core molecular activity. Kept as non-core. Supporting Evidence: PMID:11576425 Overproduction of At-HSP17.6A could increase salt and drought tolerance in file:ARATH/HSP17.6A/HSP17.6A-deep-research-falcon.md At-HSP17.6A overexpression can enhance osmotolerance in Arabidopsis. |
| GO:0009408 response to heat | IEP PMID:11576425 At-HSP17.6A, encoding a small heat-shock protein in Arabidop... | ACCEPT | Summary: The IEP annotation is based on heat-inducible expression demonstrated in PMID:11576425. Heat induction is a defining feature of sHSPs, and falcon corroborates strong HsfA1-dependent heat induction. Response to heat is a core biological process for HSP17.6A. Reason: Heat-inducible expression is directly demonstrated (PMID:11576425) and consistent with the canonical heat shock response role of this sHSP under HsfA1 control. Supporting Evidence: PMID:11576425 expression was induced by heat and osmotic stress, as well as during seed file:ARATH/HSP17.6A/HSP17.6A-deep-research-falcon.md These observations support that **HSP17.6A is a canonical heat shock response gene** under strong positive control by HsfA1 family activity. |
| GO:0009651 response to salt stress | IDA PMID:11576425 At-HSP17.6A, encoding a small heat-shock protein in Arabidop... | KEEP AS NON CORE | Summary: PMID:11576425 reported that overproduction of At-HSP17.6A increases salt (and drought) tolerance. This is a stress-protective phenotype mediated by the holdase chaperone activity rather than a salt-specific molecular function. Falcon corroborates the engineering/ overexpression relevance for abiotic stress tolerance. Reason: Salt stress tolerance is a downstream consequence of the general proteostasis/holdase function rather than a core molecular activity. Kept as non-core. Supporting Evidence: PMID:11576425 Overproduction of At-HSP17.6A could increase salt and drought tolerance in file:ARATH/HSP17.6A/HSP17.6A-deep-research-falcon.md At-HSP17.6A overexpression can enhance osmotolerance in Arabidopsis. |
| GO:0051259 protein complex oligomerization | IDA PMID:11576425 At-HSP17.6A, encoding a small heat-shock protein in Arabidop... | ACCEPT | Summary: Oligomerization is documented for At-HSP17.6A in PMID:11576425 (which UniProt Q9XIE3 cites for OLIGOMERIZATION) and is a core structural property of sHSPs underpinning the holdase mechanism. Falcon corroborates the family-level dynamic oligomerization mechanism. Reason: Oligomerization is integral to sHSP chaperone function rather than a peripheral feature. The IDA annotation is supported by PMID:11576425 and consistent with the sHSP family mechanism. Supporting Evidence: file:ARATH/HSP17.6A/HSP17.6A-deep-research-falcon.md ACD-type sHSPs form large oligomers (reported in the review as commonly **~150–800 kDa**), and these oligomers are **dynamic** and can rearrange with temperature or other conditions. |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)