amon (Q9VBC7) notes

2026-10-21 — Full re-review, independent of the ProtNLM2 predictions

No ProtNLM2 files were consulted.

Identity

• Q9VBC7 is the canonical, Swiss-Prot reviewed product of amon/CG6438 (FBgn0023179), 654 aa, PE 1. Not a fragment, isoform or alternative gene model.
• Architecture (UniProt): signal 1-21, propeptide 22-121, mature chain 122-654, peptidase S8 domain 158-483 with charge-relay triad D196/H237/S412, P-domain 491-627; no transmembrane segment. Soluble PC2 architecture.

Evolutionary placement

• PANTHER PTHR42884:SF13 "NEUROENDOCRINE CONVERTASE 2", together with human PCSK2 (P16519), mouse/rat Pcsk2 and C. elegans egl-3 (interpro/panther/PTHR42884/PTHR42884-entries.csv).
• PAINT: PC2 bilaterian node PTN000082858 carries IBDs for extracellular region, neuron projection and peptide hormone processing (donors include amon itself, P16519, MGI:97512, RGD:3273, egl-3); IRD NOTs for Golgi membrane and TGN were placed on this node, i.e. curators deliberately kept TGN/Golgi only for constitutive convertases. Serine endopeptidase activity and generic membrane come from the deep node PTN002451026.
• The PANTHER family review (PTHR42884-review.yaml) places amon in SF13; no disagreement.

Literature-grounded function

• Active dPC2 secreted from S2 cells only when coexpressed with 7B2 PMID:10749852
• Catalytic-His mutant fails to rescue hatching PMID:10436051
• AKH maturation PMID:20523747; neurohemal peptides PMID:21138435; enteroendocrine peptides PMID:21214272.
• Retina: RNAi-only, ligand processing proposed not shown PMID:28853393.

Changes in this re-review

• proteolysis (IDA, IEA): ACCEPT -> MODIFY to GO:0016486 peptide hormone processing (is_a descendant, already on gene).
• serine hydrolase activity (HDA): KEEP_AS_NON_CORE -> MODIFY to GO:0004252 (general-term rule).
• larval behavior (IEA ARBA): KEEP_AS_NON_CORE -> MODIFY to GO:0035180 larval wandering behavior.
• R8 cell fate specification (IMP): KEEP_AS_NON_CORE -> MARK_AS_OVER_ANNOTATED (indirect, non-autonomous, RNAi-only).
• neuron projection (IBA): ACCEPT -> KEEP_AS_NON_CORE.
• membrane (IBA): stays UNDECIDED, now with propagation_review (deep node, PC2 lacks TM; human PCSK2 is a donor).
• Description rewritten; core function expanded; reference_review added for all PMIDs; suggested questions/experiments added; status COMPLETE.

Relative

• Closest characterised relative by phylogeny: human PCSK2 (P16519), same PANTHER subfamily SF13 and a donor at PAINT node PTN000082858. No genes/human/PCSK2 review exists in the repo.
• Modules mentioning PCSK2: modules/leptin_melanocortin_signaling.yaml, modules/beta_cell_glucose_stimulated_insulin_secretion.yaml (mammalian; amon not a member).

2026-11-01 follow-up: Slit cleavage (FlyBase and UniProt descriptions)

• FlyBase says amon "directly cleaves sli protein"; UniProt cites one study for and one against.
  Ordan and Volk 2016 reported attenuated Slit cleavage in amon mutants
  PMID:27628033,
  but Kellermeyer et al. 2020 could not reproduce it and identified Tolkin as the Slit protease
  PMID:32994163.
• Disputed and not direct, so it is not added to the review description or annotations. FlyBase text
  recorded as a WRONG_STATEMENT source defect.