cryaa (Danio rerio) review notes

Zebrafish alpha-crystallin A chain, UniProt Q8UUZ6 (TrEMBL; the entry carries no FUNCTION line, only a rule-based subcellular location and the small heat shock protein family assignment). All functional evidence therefore comes from primary zebrafish literature rather than from UniProt.

Re-review 2026-09-29

• Reconciled the yaml against the refreshed GOA. Three rows for the obsoleted GO:0051082 unfolded protein binding (IBA plus two IDA) and one GO:0046872 metal ion binding IEA row are no longer in GOA and were dropped; a duplicate GO:0005212 IEA row under GO_REF:0000120 was replaced by the GO_REF:0000002 (InterPro:IPR003090) row that GOA now carries. The migrated GO:0140309 unfolded protein holdase activity IDA rows (PMID:15692462, PMID:22479631) were the PENDING rows and are now ACCEPT.
• Accepted GO:0140309 rather than keeping the previous review's bespoke NTR. The term's definition still describes a carrier that escorts an unfolded client ("escorts it to an acceptor molecule or to a specific location"), which does not match the small heat shock protein mechanism, but GO lists "holdase" among its synonyms and GOA has migrated this gene onto it. Overruling that would substitute our reading of a definition for the curators' decision, so the definitional mismatch is recorded as a suggested question (go-ontology issue 30552) and proposed_new_terms was removed; core_functions now uses the real term id.
• Holdase rows grounded in the zebrafish assays: PMID:15692462 and PMID:22479631, with the in vivo counterpart PMID:16728471.
• Action changes: GO:0009408 response to heat IBA ACCEPT -> KEEP_AS_NON_CORE. The node PTN000897708 is seeded mainly by inducible invertebrate sHSPs, whereas zebrafish cryaa is a constitutively expressed lens protein whose link to temperature is adaptive, not inductive PMID:15692462; a propagation_review records this as a context mismatch rather than a bad node. GO:0042026 protein refolding IBA MODIFY -> MARK_AS_OVER_ANNOTATED, avoiding the cross-aspect modification of a BP row into an MF term: the assays measure prevented aggregation, not restored client activity, and the refolding step belongs to the ATP-dependent chaperones the sHSP hands clients to.
• Kept GO:0001654 eye development IDA as MODIFY to GO:0002088: everything the cloche paper measures is lens PMID:16728471. Kept GO:0007601 visual perception NAS as MARK_AS_OVER_ANNOTATED with an explicit participation argument - cryaa neither transduces nor processes a visual stimulus.
• Nucleus rows (IBA and IEA) kept non-core, now with the honest caveat that no zebrafish localization experiment exists [file:DANRE/cryaa/cryaa-deep-research-falcon.md "I did not find direct experimental evidence specifying Cryaa's subcellular localization ... in zebrafish lens cells"], against lens-restricted expression PMID:11925526.
• GO:0043066 negative regulation of apoptotic process IBA kept non-core: node PTN002264124 is seeded by mammalian alphaA/alphaB-crystallins, and there is no zebrafish tissue context for it given the lens-restricted expression.
• Rewrote description as standalone biology and dropped the PDB entry and zinc-site claims from it (the zinc ligands are PIRSR rule-based features in UniProt and GOA no longer carries a metal ion binding row). Added reference_review to all five PMIDs; added suggested questions and experiments. This notes file did not previously exist. Validation: zero errors, zero warnings.

Alignment to the holdase new-term convention (2026-09-29)

The two GO:0140309 IDA rows were first accepted in this re-review, but that diverged from the convention used for the paralogs (cryabb) and for the other small heat-shock proteins in this repository (human CRYAA, HSPB2, HSPB3, fly Hsp26/Hsp27), which treat GO:0140309 as still carrying a carrier-specific definition (escort to an acceptor; go-ontology#30552) and request a new "holdase chaperone activity" term instead. For consistency the rows are now MODIFY with an NTR replacement, a proposed_new_terms entry was added, and the core function uses proposed_molecular_function. The experimental evidence and its interpretation are unchanged; only the target term differs.