asah2 (Danio rerio) review notes

Batch 05 curation notes

• Core interpretation: asah2 encodes neutral ceramidase, a membrane-associated zinc-dependent N-acylsphingosine amidohydrolase that hydrolyzes ceramides to sphingosine and fatty acids at neutral pH. The core function is ceramide catabolism/sphingosine production at plasma/apical and related membrane compartments.
• Key UniProt support: hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH.
• Existing GOA annotations were reviewed against this core role; broad, inferred, or downstream phenotype annotations were kept as non-core unless they overstate the direct function.

Re-review 2026-09-29

• Rebuilt all 34 existing_annotations rows from the refreshed GOA (34 rows). Removed a stale IBA row for GO:0005576 extracellular region that is no longer in GOA; resolved the newly appended IBA GO:0005886 plasma membrane row (PENDING -> ACCEPT, node PTN000292661). Added the second, duplicate ISS mitochondrion row so the yaml matches GOA.
• Replaced templated reviews (deep-research quotes and the UniProt FUNCTION line pasted under every term) with term-specific evidence. Localization rows now cite the UniProt SUBCELLULAR LOCATION line and the abstract PMID:15271994; activity rows cite PMID:15271994 and the CATALYTIC ACTIVITY line; the ceramide-process rows cite PMID:15271994.
• Cached PMID:26190575 (human nCDase crystal structure, abstract-only) to support the Zn-dependent amidase mechanism behind the zinc ion binding and amidohydrolase rows.
• Action changes: GO:0005509 calcium ion binding ISS UNDECIDED -> KEEP_AS_NON_CORE (UniProt annotates a structural Ca2+ site at residues 672/674/677 by similarity to human; not catalytic). GO:0005739 mitochondrion (IEA, ISS x2) KEEP_AS_NON_CORE -> MARK_AS_OVER_ANNOTATED (by-similarity only, mammalian evidence is overexpression-based, and the zebrafish overexpression study found ER/Golgi/plasma membrane, not mitochondria). GO:0000139 Golgi membrane and GO:0005789 ER membrane (IDA/ISS/IEA) ACCEPT -> KEEP_AS_NON_CORE (secretory-pathway transit of overexpressed type II membrane protein; site of action is the plasma membrane). GO:0005737 cytoplasm IEA KEEP_AS_NON_CORE -> MARK_AS_OVER_ANNOTATED (14-residue cytoplasmic tail only). GO:0005576 extracellular region IEA ACCEPT -> KEEP_AS_NON_CORE (exosome/secreted form by similarity to human only). GO:0007346 regulation of mitotic cell cycle ISS KEEP_AS_NON_CORE -> MARK_AS_OVER_ANNOTATED (downstream signaling outcome, no participation). GO:0006665 sphingolipid metabolic process IEA KEEP_AS_NON_CORE -> ACCEPT (broad but correct parent of the core process). Retained MARK_AS_OVER_ANNOTATED for GO:0042759 (IBA, bacterial-donor node; fatty acid is a hydrolysis leaving group) and GO:0046513 ceramide biosynthetic process (ISS, in vitro reverse reaction; UniProt PhysiologicalDirection=left-to-right).
• GO:0016324 apical plasma membrane IDA accepted deferring to ZFIN: the abstract states plasma-membrane distribution and UniProt records "Detected in intestine (at protein level)" from the same paper; apical detail is in the full text, which is not cached.
• Rewrote description as standalone biology; core_functions now lists plasma membrane and apical plasma membrane only (Golgi dropped as non-core). Added reference_review to both PMIDs. Validation: zero errors, zero warnings.