id: Q9PUR2 gene_symbol: cryaba product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:7955 label: Danio rerio description: '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.' existing_annotations: - term: id: GO:0042026 label: protein refolding evidence_type: IBA original_reference_id: GO_REF:0000033 review: 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.' action: MARK_AS_OVER_ANNOTATED 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 source_entities: - source_id: PANTHER:PTN000897708 source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET comment: 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. supported_by: - &id001 reference_id: PMID:15692462 supporting_text: 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 - &id010 reference_id: PMID:15692462 supporting_text: The chaperone-like activities of the two zebrafish alpha-crystallins were highly divergent, with alphaA-crystallin showing much greater activity than alphaB-crystallin qualifier: involved_in supporting_entities: - FB:FBgn0001223 - FB:FBgn0001224 - FB:FBgn0001225 - FB:FBgn0001226 - FB:FBgn0011296 - FB:FBgn0031037 - FB:FBgn0035817 - PANTHER:PTN000897708 - term: id: GO:0005634 label: nucleus evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: Nucleus, propagated from node PTN000897708 on the strength of mammalian alpha-crystallin reports; no zebrafish experiment addresses the subcellular localization of cryaba. action: KEEP_AS_NON_CORE 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. supported_by: - &id003 reference_id: PMID:16420472 supporting_text: while zebrafish alphaB1 adopted a more restricted, nonchaperone role in the lens - &id002 reference_id: PMID:15692462 supporting_text: 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 qualifier: is_active_in supporting_entities: - MGI:MGI:96240 - PANTHER:PTN000897708 - UniProtKB:O14558 - UniProtKB:P02489 - UniProtKB:P02511 - UniProtKB:P04792 - UniProtKB:Q16082 - ZFIN:ZDB-GENE-030326-4 - term: id: GO:0005737 label: cytoplasm evidence_type: IBA original_reference_id: GO_REF:0000033 review: 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.' action: ACCEPT 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. supported_by: - &id005 reference_id: PMID:38705506 supporting_text: lens-specific zebrafish αBa-crystallin plays the leading role in preventing age-related cataract - *id001 - &id006 reference_id: PMID:16420472 supporting_text: Zebrafish is the first species known to express two different alphaB-crystallins qualifier: is_active_in supporting_entities: - FB:FBgn0001223 - FB:FBgn0001224 - FB:FBgn0001225 - FB:FBgn0001226 - FB:FBgn0011296 - FB:FBgn0031037 - MGI:MGI:88515 - MGI:MGI:88516 - MGI:MGI:96240 - PANTHER:PTN000897708 - RGD:2414 - RGD:61306 - UniProtKB:O14558 - UniProtKB:P02470 - UniProtKB:P02489 - UniProtKB:P02511 - UniProtKB:P04792 - UniProtKB:Q00649 - UniProtKB:Q16082 - WB:WBGene00002011 - WB:WBGene00002013 - WB:WBGene00002015 - WB:WBGene00002016 - WB:WBGene00002023 - WB:WBGene00004798 - ZFIN:ZDB-GENE-030326-4 - term: id: GO:0043066 label: negative regulation of apoptotic process evidence_type: IBA original_reference_id: GO_REF:0000033 review: 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. action: KEEP_AS_NON_CORE 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. supported_by: - &id004 reference_id: PMID:16420472 supporting_text: not constitutively expressed in nervous or muscular tissue and has reduced chaperone-like activity - *id002 - *id003 qualifier: involved_in supporting_entities: - MGI:MGI:88515 - MGI:MGI:88516 - MGI:MGI:96240 - PANTHER:PTN002264124 - RGD:2414 - RGD:621554 - UniProtKB:P02489 - UniProtKB:P02511 - UniProtKB:P04792 - term: id: GO:0009408 label: response to heat evidence_type: IBA original_reference_id: GO_REF:0000033 review: 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. action: KEEP_AS_NON_CORE 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 source_entities: - source_id: PANTHER:PTN000897708 source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET comment: Node seeded mainly by inducible invertebrate sHSPs; the zebrafish alphaB1 branch is a constitutively expressed lens protein that lost extralenticular expression after the duplication. supported_by: - *id001 - *id004 - *id002 qualifier: involved_in supporting_entities: - FB:FBgn0001223 - FB:FBgn0001224 - FB:FBgn0001225 - FB:FBgn0001226 - FB:FBgn0001227 - FB:FBgn0001229 - FB:FBgn0011296 - FB:FBgn0035817 - FB:FBgn0035982 - PANTHER:PTN000897708 - UniProtKB:Q00649 - WB:WBGene00002015 - WB:WBGene00002016 - WB:WBGene00002018 - WB:WBGene00002019 - WB:WBGene00004798 - ZFIN:ZDB-GENE-030326-4 - term: id: GO:0005212 label: structural constituent of eye lens evidence_type: IEA original_reference_id: GO_REF:0000002 review: 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. action: ACCEPT 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. supported_by: - &id007 reference_id: PMID:38705506 supporting_text: loss of the αBa-crystallin gene cryaba led to an increase in lens opacity compared to cryaa null fish at 24 months of age - *id005 - *id003 - reference_id: file:DANRE/cryaba/cryaba-deep-research-falcon.md supporting_text: adult lens proteomics (parallel reaction monitoring) detected an **αBa‑crystallin peptide** in wild type lenses that was **absent in cryaba−/−** lenses reference_section_type: RESULTS qualifier: enables supporting_entities: - InterPro:IPR003090 - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000117 review: 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.' action: ACCEPT 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. supported_by: - *id005 - *id001 - *id006 - reference_id: file:DANRE/cryaba/cryaba-deep-research-falcon.md supporting_text: adult lens proteomics (parallel reaction monitoring) detected an **αBa‑crystallin peptide** in wild type lenses that was **absent in cryaba−/−** lenses reference_section_type: RESULTS qualifier: located_in supporting_entities: - ARBA:ARBA00026971 - term: id: GO:0036438 label: maintenance of lens transparency evidence_type: IMP original_reference_id: PMID:38705506 review: 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.' action: ACCEPT 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.' supported_by: - *id007 - *id005 - reference_id: PMID:38705506 supporting_text: None of the three α-crystallin mutants showed a compensatory increase in the expression of the remaining two crystallins - reference_id: PMID:38705506 supporting_text: the protective role for cryaba becomes more important during lens aging qualifier: acts_upstream_of_or_within supporting_entities: - ZFIN:ZDB-GENO-250219-5 - term: id: GO:0007519 label: skeletal muscle tissue development evidence_type: IMP original_reference_id: PMID:25866181 review: 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. action: KEEP_AS_NON_CORE 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. supported_by: - &id009 reference_id: PMID:25866181 supporting_text: we here specifically inactivated known human MFM disease genes and evaluated the resulting muscular and cardiac phenotypes functionally and structurally - &id008 reference_id: PMID:25866181 supporting_text: targeted ablation of MFM genes in zebrafish led to compromised skeletal muscle function mostly due to myofibrillar degeneration as well as severe heart failure - *id004 qualifier: acts_upstream_of_or_within supporting_entities: - ZFIN:ZDB-MRPHLNO-150828-3 - term: id: GO:0007626 label: locomotory behavior evidence_type: IMP original_reference_id: PMID:25866181 review: summary: Locomotory behavior, scored as impaired swimming/muscle function after morpholino knockdown in the same screen. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - *id008 - *id009 qualifier: acts_upstream_of_or_within supporting_entities: - ZFIN:ZDB-MRPHLNO-150828-3 - term: id: GO:0030239 label: myofibril assembly evidence_type: IMP original_reference_id: PMID:25866181 review: summary: Myofibril assembly, from the same myofibrillar myopathy morpholino screen; knockdown of the MFM genes caused myofibrillar degeneration. action: KEEP_AS_NON_CORE 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.' supported_by: - *id008 - reference_id: PMID:25866181 supporting_text: MFM gene-deficient zebrafish showed pronounced gene-specific phenotypic and structural differences - *id004 qualifier: acts_upstream_of_or_within supporting_entities: - ZFIN:ZDB-MRPHLNO-150828-3 - term: id: GO:0060047 label: heart contraction evidence_type: IMP original_reference_id: PMID:25866181 review: summary: Heart contraction, scored as cardiac failure after morpholino knockdown in the myofibrillar myopathy screen. action: MARK_AS_OVER_ANNOTATED 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.' supported_by: - *id008 - *id004 - *id009 qualifier: acts_upstream_of_or_within supporting_entities: - ZFIN:ZDB-MRPHLNO-150828-3 - term: id: GO:0005886 label: plasma membrane evidence_type: IDA original_reference_id: PMID:18406404 review: 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. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:18406404 supporting_text: Lengsin expression in zebrafish follows the temporal expression of the alphaA- alphaB1- and betaB1-crystallin proteins in the lens - reference_id: PMID:18406404 supporting_text: 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 qualifier: located_in - term: id: GO:0140309 label: unfolded protein holdase activity evidence_type: IDA original_reference_id: PMID:15692462 review: 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.' action: MODIFY proposed_replacement_terms: - id: NTR label: holdase chaperone activity 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.' supported_by: - *id001 - *id010 - *id007 qualifier: enables references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000043 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: PMID:38705506 title: Loss of αBa-crystallin, but not αA-crystallin, increases age-related cataract in the zebrafish lens. findings: - statement: cryaba null fish develop more lens opacity than cryaa nulls by 24 months. supporting_text: loss of the αBa-crystallin gene cryaba led to an increase in lens opacity compared to cryaa null fish at 24 months of age - statement: cryaba is the leading alpha-crystallin protecting against age-related cataract. supporting_text: lens-specific zebrafish αBa-crystallin plays the leading role in preventing age-related cataract - statement: The protective role of cryaba grows in importance during lens aging. supporting_text: the protective role for cryaba becomes more important during lens aging - statement: No compensatory upregulation of the other crystallins occurs in the mutants. supporting_text: None of the three α-crystallin mutants showed a compensatory increase in the expression of the remaining two crystallins reference_review: relevance: HIGH correctness: VERIFIED review_notes: Title matches the cached record. Zebrafish null-mutant study and the strongest evidence for the maintenance of lens transparency annotation; the absence of compensation is what makes the phenotype attributable to cryaba. Abstract-only cache. - id: PMID:15692462 title: 'Zebrafish alpha-crystallins: protein structure and chaperone-like activity compared to their mammalian orthologs.' findings: - statement: Chaperone-like activity was assayed as prevention of chemically induced aggregation between 25 and 40 degrees C. supporting_text: 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 - statement: Zebrafish alphaB-crystallin is a much weaker chaperone than zebrafish alphaA-crystallin. supporting_text: The chaperone-like activities of the two zebrafish alpha-crystallins were highly divergent, with alphaA-crystallin showing much greater activity than alphaB-crystallin - statement: Reduced chaperone function and lack of extralenticular expression indicate a different physiological role from the mammalian ortholog. supporting_text: 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 reference_review: relevance: HIGH correctness: VERIFIED review_notes: Title matches PubMed; the source of the GO:0140309 IDA for this gene and the reason the holdase annotation carries a quantitative caveat. Abstract-only cache. - id: PMID:16420472 title: Gene duplication and separation of functions in alphaB-crystallin from zebrafish (Danio rerio). findings: - statement: Zebrafish alphaB1-crystallin is not constitutively expressed in nervous or muscular tissue and has reduced chaperone-like activity. supporting_text: not constitutively expressed in nervous or muscular tissue and has reduced chaperone-like activity - statement: After duplication alphaB2 kept the widespread protective role while alphaB1 took a restricted lens role. supporting_text: while zebrafish alphaB1 adopted a more restricted, nonchaperone role in the lens - statement: Zebrafish is the first species known to express two alphaB-crystallins. supporting_text: Zebrafish is the first species known to express two different alphaB-crystallins reference_review: relevance: HIGH correctness: VERIFIED review_notes: 'Title matches PubMed. The paralog paper: it establishes that cryaba (alphaB1) is the lens-restricted duplicate, which is decisive for how the muscle and heart annotations are graded. Note that its broad heart/brain/muscle expression data describe alphaB2 (cryabb), not this gene; the previous description had these attributed the wrong way round. Abstract-only cache.' - id: PMID:25866181 title: In vivo characterization of human myofibrillar myopathy genes in zebrafish. findings: - statement: Human myofibrillar myopathy genes were knocked down in zebrafish and muscle and cardiac phenotypes scored. supporting_text: we here specifically inactivated known human MFM disease genes and evaluated the resulting muscular and cardiac phenotypes functionally and structurally - statement: Knockdown compromised skeletal muscle function through myofibrillar degeneration and caused heart failure. supporting_text: targeted ablation of MFM genes in zebrafish led to compromised skeletal muscle function mostly due to myofibrillar degeneration as well as severe heart failure - statement: Phenotypes differed between the genes tested. supporting_text: MFM gene-deficient zebrafish showed pronounced gene-specific phenotypic and structural differences reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Title matches PubMed. A morpholino screen; the abstract reports phenotypes at the level of the gene set rather than per gene, so the cryaba-specific detail is in the full text and is taken on the ZFIN curator’s reading. This is the source of all four muscle, heart and behaviour rows. Abstract-only cache. - id: PMID:18406404 title: Lengsin expression and function during zebrafish lens formation. findings: - statement: Lengsin expression follows the temporal expression of alphaA-, alphaB1- and betaB1-crystallin proteins in the lens. supporting_text: Lengsin expression in zebrafish follows the temporal expression of the alphaA- alphaB1- and betaB1-crystallin proteins in the lens - statement: In the adult lens the protein studied is restricted to cortical fibres and co-localizes with actin at lateral cell faces. supporting_text: 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 reference_review: relevance: LOW correctness: VERIFIED review_notes: Title matches PubMed. The paper is about lengsin, not cryaba, but its immunolocalization work in lens fibre cells is what ZFIN used for the cryaba plasma membrane IDA. Abstract-only cache, so the supporting figure cannot be checked here; the row is kept and graded non-core rather than challenged. - id: file:DANRE/cryaba/cryaba-uniprot.txt title: UniProtKB entry Q9PUR2 for Danio rerio cryaba findings: - statement: Alpha-crystallin B chain of the small heat shock protein family. record_section: ["CC:SIMILARITY"] supporting_text: Belongs to the small heat shock protein (HSP20) family. - id: file:DANRE/cryaba/cryaba-deep-research-falcon.md title: 'Falcon (Edison) deep research report: zebrafish cryaba (Q9PUR2) functional annotation of alphaBa-crystallin' findings: - statement: Lens proteomics detected an alphaBa-crystallin peptide in wild-type adult lenses that was absent in cryaba null lenses, confirming the gene product is a lens protein in vivo. supporting_text: adult lens proteomics (parallel reaction monitoring) detected an **αBa‑crystallin peptide** in wild type lenses that was **absent in cryaba−/−** lenses reference_section_type: RESULTS reference_review: relevance: LOW correctness: VERIFIED review_notes: Generated literature survey; the zebrafish claims used here are taken from the five primary papers directly. core_functions: - description: 'ATP-independent holdase chaperone of the lens: binds partly unfolded crystallins and keeps them soluble, preventing the aggregation that produces lens opacity. Measurably weaker in vitro than the alphaA paralog, but the loss of cryaba is what increases cataract in aging zebrafish.' proposed_molecular_function: holdase chaperone activity supported_by: - *id001 - *id010 - *id007 - *id005 directly_involved_in: - id: GO:0036438 label: maintenance of lens transparency locations: - id: GO:0005737 label: cytoplasm - description: 'Alpha-crystallin structural protein of the lens: one of the bulk cytoplasmic proteins of lens fibre cells, and the lens-restricted product of the duplicated zebrafish alphaB-crystallin pair.' supported_by: - *id003 - *id005 - *id006 molecular_function: id: GO:0005212 label: structural constituent of eye lens directly_involved_in: - id: GO:0036438 label: maintenance of lens transparency locations: - id: GO:0005737 label: cytoplasm proposed_new_terms: - proposed_name: holdase chaperone activity proposed_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. proposed_parent: id: GO:0003674 label: molecular_function supported_by: - reference_id: PMID:15692462 supporting_text: 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 - reference_id: PMID:15692462 supporting_text: The chaperone-like activities of the two zebrafish alpha-crystallins were highly divergent, with alphaA-crystallin showing much greater activity than alphaB-crystallin suggested_questions: - question: 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. - question: 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. suggested_experiments: - description: 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. - description: 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.