tpp1 review notes

• Curated in DANRE batch 04. Tpp1 has a clear lysosomal tripeptidyl-peptidase core function. I kept CNS development, neurogenesis, and locomotory behavior as non-core phenotypes from the zebrafish CLN2 model rather than treating them as the gene product activity PMID:23587805.
• Follow-up: broad endopeptidase activity is now non-core because tripeptidyl-peptidase activity is the informative function.

Re-review 2026-09-29

• Resolved the 6 PENDING rows added after the GOA refresh: is_active_in lysosome (IBA, PTN001022357) and lysosomal protein catabolic process GO:1905146 (IBA) are ACCEPTed as core; GO:1905146 is now the process term in core_functions because Tpp1 itself performs a step of lysosomal protein breakdown (generates tripeptides from the products of lysosomal proteinases) and the mutant shows the storage phenotype expected when that step fails PMID:23587805. The two morpholino-based IMP rows each for CNS development and neurogenesis (ZDB-MRPHLNO-130718-1/-2) are KEEP_AS_NON_CORE, matching the mutant-based rows; UniProt records the morphant phenotype [file:tpp1-uniprot.txt "Morpholino knockdown of the protein in embryos"].
• Action change: locomotory behavior GO:0007626 (IMP) moved from KEEP_AS_NON_CORE to MARK_AS_OVER_ANNOTATED. The seizure-like hyperactivity and later motor impairment are behavioural read-outs of neurodegeneration PMID:23587805; a lysosomal peptidase does no work in a behaviour. CNS development and neurogenesis stay non-core: Tpp1 does not perform a step of those processes, but housekeeping lysosomal proteolysis is required for neuronal survival and proliferation and the acts_upstream_of_or_within qualifier already encodes the indirectness.
• Removed the templated five-quote block (FUNCTION line + "SUBCELLULAR LOCATION: Lysosome" + "deficient in tripeptidyl peptidase 1" pasted under every term). Localization rows now cite the SUBCELLULAR LOCATION line and the hypertrophic-lysosome phenotype; activity rows cite the CATALYTIC ACTIVITY line and the mutant enzyme deficiency; the endopeptidase rows cite the "also has endopeptidase activity" clause. Deep-research quotes were kept only where they add full-text detail not in the abstract-only cache (the Arg-Ala-Phe-ACC assay).
• PMID:14609438 (full text cached) is used for the ISS row: it identified and corrected the zebrafish CLN2 EST and shows the sedolisin Ser/Glu/Asp triad is conserved PMID:14609438. Added reference_review to both PMIDs (both VERIFIED against the cached titles; PMID:23587805 is abstract-only).
• Description rewritten as standalone biology (zymogen, autocatalytic activation, tripeptidyl exopeptidase with weaker endopeptidase activity, CLN2 model phenotype).
• Validation: zero errors, zero warnings.