cryaba encodes zebrafish alpha-crystallin B chain a (alphaB1-crystallin), a 168-residue small heat shock protein (HSP20 family) built around a central alpha-crystallin domain. Zebrafish carry two alphaB-crystallin genes from the teleost genome duplication, and the functions separated between them: cryaba became a lens-restricted protein that is not constitutively expressed in nervous or muscular tissue and has reduced in vitro chaperone activity, while the cryabb paralog retained the broad, stress-responsive expression of mammalian CRYAB. In the lens cryaba is a soluble cytoplasmic alpha-crystallin that acts as an ATP-independent holdase, binding partly unfolded proteins and keeping them soluble, and it is also detected in association with fibre-cell membranes. Its importance is developmental-stage dependent: cryaa dominates the embryonic lens, whereas cryaba becomes the principal protector later, and fish lacking it develop more lens opacity with age than cryaa nulls.
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. This is mechanistically distinct from foldase activity (GO:0044183) and from carrier-holdase activity (GO:0140309).
Justification: cryaba is the lens-restricted zebrafish alphaB1-crystallin paralog whose recombinant protein shows reduced but measurable aggregation-suppressing activity without ATP or refolding. 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. The same request is made for the paralogs cryaa and cryabb.
Parent term: molecular_function
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0042026 protein refolding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Protein refolding, propagated from the broad small heat shock protein node PTN000897708 (mostly Drosophila Hsps). Alpha-crystallins are ATP-independent holdases: they keep clients soluble, while restoring client activity is done by ATP-dependent chaperone systems. Reason: Every assay of zebrafish alphaB1-crystallin measures prevention of aggregation, not recovery of client activity, and this paralog is the weaker chaperone of the two zebrafish alpha-crystallins. Holding clients soluble contributes to refolding by other chaperones but is not the refolding step; GO:0140309, annotated here by IDA, names the activity the protein actually has. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION GRANULARITY MISMATCH Sources checked: PANTHER:PTN000897708 SUPPORTS SOURCE BUT NOT TARGET The sHSP node is correctly placed for chaperone-like function, but the refolding process term ascribes to the sHSP a step carried out by the ATP-dependent chaperones that take its clients. Supporting Evidence: PMID:15692462 The chaperone-like activities of zebrafish and human alpha-crystallins were compared by assaying their ability to prevent the chemically induced aggregation of several target proteins at temperatures between 25 degrees C and 40 degrees C PMID:15692462 The chaperone-like activities of the two zebrafish alpha-crystallins were highly divergent, with alphaA-crystallin showing much greater activity than alphaB-crystallin |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Nucleus, propagated from node PTN000897708 on the strength of mammalian alpha-crystallin reports; no zebrafish experiment addresses the subcellular localization of cryaba. Reason: Nuclear pools are documented for mammalian alphaB-crystallin under stress, and cryaba is inside the clade the node covers, so the inference is not unfounded. But this paralog is a lens protein with a restricted role, and no compartment-resolved data exist for it in zebrafish, so a nuclear role is not core. Supporting Evidence: PMID:16420472 while zebrafish alphaB1 adopted a more restricted, nonchaperone role in the lens PMID:15692462 The reduced chaperone-like function of zebrafish alphaB-crystallin and its lack of extralenticular expression indicates that it plays a different physiological role from its mammalian ortholog |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm: alphaB1-crystallin is a soluble protein of lens fibre cell cytoplasm, where the alpha-crystallins accumulate as bulk lens protein. Node PTN000897708, with zebrafish cryaba itself among the seeding descendants. Reason: The chaperone assays use soluble recombinant protein, the protein is quantified as a fraction of total lens protein, and its protective role against cataract is exercised on cytoplasmic crystallin clients. This is where the gene product acts. Supporting Evidence: PMID:38705506 lens-specific zebrafish Ξ±Ba-crystallin plays the leading role in preventing age-related cataract PMID:15692462 The chaperone-like activities of zebrafish and human alpha-crystallins were compared by assaying their ability to prevent the chemically induced aggregation of several target proteins at temperatures between 25 degrees C and 40 degrees C PMID:16420472 Zebrafish is the first species known to express two different alphaB-crystallins |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process, propagated from node PTN002264124, which is seeded by mammalian alphaA- and alphaB-crystallins whose anti-apoptotic activity is documented in cell culture. Reason: The node placement is defensible for the mammalian donors, but zebrafish alphaB1-crystallin is the paralog that lost the broad extralenticular expression of mammalian CRYAB, so there is no tissue context in this species for an anti-apoptotic role. Retained as a family-level inference, not a core process. Supporting Evidence: PMID:16420472 not constitutively expressed in nervous or muscular tissue and has reduced chaperone-like activity PMID:15692462 The reduced chaperone-like function of zebrafish alphaB-crystallin and its lack of extralenticular expression indicates that it plays a different physiological role from its mammalian ortholog PMID:16420472 while zebrafish alphaB1 adopted a more restricted, nonchaperone role in the lens |
| GO:0009408 response to heat | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Response to heat, propagated from node PTN000897708, whose donors are largely heat-inducible invertebrate small heat shock proteins. Zebrafish alphaB1-crystallin is a constitutive lens protein with reduced chaperone-like activity relative to its mammalian ortholog. Reason: The family assignment is correct and chaperone activity was measured across 25-40 degrees C, so heat is a relevant variable; but the evidence in this lineage concerns constitutive lens protection rather than induction by heat stress, and this paralog specifically lost the stress-responsive extralenticular expression. Kept as non-core. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN000897708 SUPPORTS SOURCE BUT NOT TARGET Node seeded mainly by inducible invertebrate sHSPs; the zebrafish alphaB1 branch is a constitutively expressed lens protein that lost extralenticular expression after the duplication. Supporting Evidence: PMID:15692462 The chaperone-like activities of zebrafish and human alpha-crystallins were compared by assaying their ability to prevent the chemically induced aggregation of several target proteins at temperatures between 25 degrees C and 40 degrees C PMID:16420472 not constitutively expressed in nervous or muscular tissue and has reduced chaperone-like activity PMID:15692462 The reduced chaperone-like function of zebrafish alphaB-crystallin and its lack of extralenticular expression indicates that it plays a different physiological role from its mammalian ortholog |
| GO:0005212 structural constituent of eye lens | IEA GO_REF:0000002 | ACCEPT | Summary: Structural constituent of eye lens, mapped from InterPro IPR003090 (alpha-crystallin). Alpha-crystallins are bulk lens proteins, and this paralog is the lens-restricted one of the two zebrafish alphaB-crystallins. Reason: The gene product is a lens-expressed alpha-crystallin whose loss increases lens opacity with age, which is the functional signature of a lens structural/protective protein. Core molecular function alongside the holdase activity. Supporting Evidence: PMID:38705506 loss of the Ξ±Ba-crystallin gene cryaba led to an increase in lens opacity compared to cryaa null fish at 24 months of age PMID:38705506 lens-specific zebrafish Ξ±Ba-crystallin plays the leading role in preventing age-related cataract PMID:16420472 while zebrafish alphaB1 adopted a more restricted, nonchaperone role in the lens file:DANRE/cryaba/cryaba-deep-research-falcon.md adult lens proteomics (parallel reaction monitoring) detected an **Ξ±Baβcrystallin peptide** in wild type lenses that was **absent in cryabaβ/β** lenses |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: Cytoplasm: alphaB1-crystallin is a soluble protein of lens fibre cell cytoplasm, where the alpha-crystallins accumulate as bulk lens protein. ARBA machine-learning mapping; the UniProt entry for this protein carries no subcellular location line of its own. Reason: The chaperone assays use soluble recombinant protein, the protein is quantified as a fraction of total lens protein, and its protective role against cataract is exercised on cytoplasmic crystallin clients. This is where the gene product acts. Supporting Evidence: PMID:38705506 lens-specific zebrafish Ξ±Ba-crystallin plays the leading role in preventing age-related cataract PMID:15692462 The chaperone-like activities of zebrafish and human alpha-crystallins were compared by assaying their ability to prevent the chemically induced aggregation of several target proteins at temperatures between 25 degrees C and 40 degrees C PMID:16420472 Zebrafish is the first species known to express two different alphaB-crystallins file:DANRE/cryaba/cryaba-deep-research-falcon.md adult lens proteomics (parallel reaction monitoring) detected an **Ξ±Baβcrystallin peptide** in wild type lenses that was **absent in cryabaβ/β** lenses |
| GO:0036438 maintenance of lens transparency | IMP PMID:38705506 Loss of Ξ±Ba-crystallin, but not Ξ±A-crystallin, increases age... | ACCEPT | Summary: Maintenance of lens transparency: cryaba null zebrafish develop more lens opacity by 24 months than cryaa nulls, and no compensatory upregulation of the other alpha-crystallins occurs, so the effect is attributable to loss of this gene. Reason: Direct zebrafish genetic evidence, and the participation is real rather than incidental: the protein keeps lens crystallins soluble, which is what transparency consists of. Core process for this gene, and the reason the 2024 study calls cryaba the leading protector against age-related cataract. Supporting Evidence: PMID:38705506 loss of the Ξ±Ba-crystallin gene cryaba led to an increase in lens opacity compared to cryaa null fish at 24 months of age PMID:38705506 lens-specific zebrafish Ξ±Ba-crystallin plays the leading role in preventing age-related cataract PMID:38705506 None of the three Ξ±-crystallin mutants showed a compensatory increase in the expression of the remaining two crystallins PMID:38705506 the protective role for cryaba becomes more important during lens aging |
| GO:0007519 skeletal muscle tissue development | IMP PMID:25866181 In vivo characterization of human myofibrillar myopathy gene... | KEEP AS NON CORE | Summary: Skeletal muscle tissue development, from a morpholino screen that knocked down zebrafish orthologs of human myofibrillar myopathy genes, including this one, and scored muscle structure and function. Reason: Small heat shock proteins plausibly do work in muscle by chaperoning sarcomeric client proteins, which is the basis of CRYAB myofibrillar myopathy in humans, so the annotation is not merely a downstream readout. But the phenotype is morphant-derived in a screen, and this paralog is reported not to be constitutively expressed in muscular tissue, the broad role having been retained by the cryabb paralog instead. Kept, but not as a core process. Supporting Evidence: PMID:25866181 we here specifically inactivated known human MFM disease genes and evaluated the resulting muscular and cardiac phenotypes functionally and structurally PMID:25866181 targeted ablation of MFM genes in zebrafish led to compromised skeletal muscle function mostly due to myofibrillar degeneration as well as severe heart failure PMID:16420472 not constitutively expressed in nervous or muscular tissue and has reduced chaperone-like activity |
| GO:0007626 locomotory behavior | IMP PMID:25866181 In vivo characterization of human myofibrillar myopathy gene... | MARK AS OVER ANNOTATED | Summary: Locomotory behavior, scored as impaired swimming/muscle function after morpholino knockdown in the same screen. Reason: The gene product does no work in generating or controlling behaviour; reduced locomotion is the whole-animal consequence of compromised skeletal muscle, which the muscle annotations already record. Annotating behaviour here adds no information about the gene product and propagates a phenotype two steps removed from its molecular activity. Supporting Evidence: PMID:25866181 targeted ablation of MFM genes in zebrafish led to compromised skeletal muscle function mostly due to myofibrillar degeneration as well as severe heart failure PMID:25866181 we here specifically inactivated known human MFM disease genes and evaluated the resulting muscular and cardiac phenotypes functionally and structurally |
| GO:0030239 myofibril assembly | IMP PMID:25866181 In vivo characterization of human myofibrillar myopathy gene... | KEEP AS NON CORE | Summary: Myofibril assembly, from the same myofibrillar myopathy morpholino screen; knockdown of the MFM genes caused myofibrillar degeneration. Reason: Chaperoning of sarcomeric proteins is a mechanism by which an sHSP could contribute to myofibril integrity, so this is the muscle annotation with the most plausible participation. The same caveats apply: morphant evidence from a screen, and an expression pattern for this paralog that argues against a constitutive muscle role in zebrafish. Supporting Evidence: PMID:25866181 targeted ablation of MFM genes in zebrafish led to compromised skeletal muscle function mostly due to myofibrillar degeneration as well as severe heart failure PMID:25866181 MFM gene-deficient zebrafish showed pronounced gene-specific phenotypic and structural differences PMID:16420472 not constitutively expressed in nervous or muscular tissue and has reduced chaperone-like activity |
| GO:0060047 heart contraction | IMP PMID:25866181 In vivo characterization of human myofibrillar myopathy gene... | MARK AS OVER ANNOTATED | Summary: Heart contraction, scored as cardiac failure after morpholino knockdown in the myofibrillar myopathy screen. Reason: Failing the participation test: contraction is performed by the sarcomere, and the gene product at most maintains its components. The paper itself frames the cardiac phenotype as a consequence of myofibrillar degeneration, so this is an organ-level readout of the structural defect already captured by the myofibril assembly annotation, obtained in morphants of a paralog that is not constitutively expressed in muscle. Supporting Evidence: PMID:25866181 targeted ablation of MFM genes in zebrafish led to compromised skeletal muscle function mostly due to myofibrillar degeneration as well as severe heart failure PMID:16420472 not constitutively expressed in nervous or muscular tissue and has reduced chaperone-like activity PMID:25866181 we here specifically inactivated known human MFM disease genes and evaluated the resulting muscular and cardiac phenotypes functionally and structurally |
| GO:0005886 plasma membrane | IDA PMID:18406404 Lengsin expression and function during zebrafish lens format... | KEEP AS NON CORE | Summary: Plasma membrane, annotated by ZFIN from the zebrafish Lengsin study, whose immunolocalization work in lens fibre cells also tracked alphaB1-crystallin. Membrane association of alpha-crystallins in lens fibre cells is a known property; the cached record is abstract-only, so the specific figure supporting it is not visible here. Reason: The curator read the full text and the paper does immunolocalize crystallins in lens fibre cells, so the observation is accepted rather than second-guessed. But the bulk of the protein is soluble cytoplasmic, which is where the chaperone and lens-protective functions are exercised, so membrane association is retained as a non-core location. Supporting Evidence: PMID:18406404 Lengsin expression in zebrafish follows the temporal expression of the alphaA- alphaB1- and betaB1-crystallin proteins in the lens PMID:18406404 In the adult lens, Lengsin is restricted to a narrow band of cortical fibers and co-localizes with actin at the lateral faces of these interdigitating cells |
| GO:0140309 unfolded protein holdase activity | IDA PMID:15692462 Zebrafish alpha-crystallins: protein structure and chaperone... | MODIFY | Summary: Unfolded protein holdase activity: purified recombinant zebrafish alphaB1-crystallin prevented the chemically induced aggregation of denaturing target proteins between 25 and 40 degrees C, though considerably less effectively than zebrafish alphaA-crystallin. Reason: Directly demonstrated for this protein, and it is the activity that explains the in vivo phenotype: loss of cryaba increases lens opacity with age, which is what failure to keep crystallins soluble looks like. Accepted as a core molecular function with the explicit caveat that the measured activity is markedly lower than that of the alphaA paralog. The term itself is the problem rather than the evidence: GO:0140309 retains a carrier definition requiring escort of the client to an acceptor molecule or location (go-ontology#30552), which was not measured. The replacement is the proposed holdase chaperone activity term listed under proposed_new_terms, the same request carried by the paralogs cryaba and cryabb; when GO creates it this row should move to it. Proposed replacements: holdase chaperone activity Supporting Evidence: PMID:15692462 The chaperone-like activities of zebrafish and human alpha-crystallins were compared by assaying their ability to prevent the chemically induced aggregation of several target proteins at temperatures between 25 degrees C and 40 degrees C PMID:15692462 The chaperone-like activities of the two zebrafish alpha-crystallins were highly divergent, with alphaA-crystallin showing much greater activity than alphaB-crystallin PMID:38705506 loss of the Ξ±Ba-crystallin gene cryaba led to an increase in lens opacity compared to cryaa null fish at 24 months of age |
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Download this section (compressed HTML)Q: Is cryaba expressed in zebrafish skeletal or cardiac muscle at any stage? The four muscle, heart and behaviour annotations rest on a morpholino screen, while the paralog study reports that alphaB1-crystallin is not constitutively expressed in muscular tissue and that cryabb retained that role. A stage-resolved expression measurement would settle whether those rows belong on this gene or on its paralog.
Q: Does GO:0140309 unfolded protein holdase activity, defined as a carrier activity that escorts an unfolded client to an acceptor or location, correctly describe a small heat shock protein that simply retains clients in a soluble state? GOA migrated this gene onto the term after GO:0051082 was obsoleted.
Experiment: Re-test the muscle and cardiac phenotypes in a stable cryaba null line rather than morphants, and in parallel in a cryabb null, to establish which paralog carries the myofibrillar myopathy-related function in zebrafish.
Experiment: Quantify crystallin solubility and lens proteome composition in aging cryaba null lenses, testing whether the increased opacity follows from aggregation of specific client crystallins that the protein holds in solution.
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