id: A0A0B4K7P3
gene_symbol: CG43124
taxon:
  id: NCBITaxon:7227
  label: Drosophila melanogaster
status: COMPLETE
description: The predicted serine-type endopeptidase activity is contradicted by loss of essential catalytic-triad
  residues in the exact CG43124 polypeptide. The trypsin-like sequence supports a noncatalytic homolog,
  not an active serine protease.
source_documents:
- genes/DROME/CG43124/CG43124-protnlm-source.json
- genes/DROME/CG43124/CG43124-uniprot.txt
- genes/DROME/CG43124/CG43124-flybase.txt
- genes/DROME/CG43124/CG43124-bioinformatics/RESULTS.md
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-08
  source_reference_id: file:DROME/CG43124/CG43124-protnlm-source.json
  predicted_term:
    id: GO:0004252
    label: serine-type endopeptidase activity
  predicted_term_type: GO_MF
  review:
    assessment: NPI
    confidence_score: 0
    error_type: PSEUDOENZYME_OVERANNOTATION
    summary: The exact target is the single 245-residue CG43124-PA polypeptide. Reproducible PF00089 profile
      alignment maps the essential trypsin catalytic histidine and aspartate to target Ser69 and Asn112
      within a significant homologous segment; active bovine trypsin provides a successful positive control.
      The catalytic-serine region is poorly aligned, so a third substitution is not asserted. These two
      replacements contradict conventional serine endopeptidase chemistry and support a noncatalytic homolog.
      The original prediction has model score 0.98 and phmmer donor Q90WD8, toad ovochymase-2; fold similarity
      to this protease does not restore the missing target catalytic residues. Target GOA contains an
      explicit NOT annotation for the same activity, consistent with this independent analysis. Opposite polarity is not an equivalent existing positive annotation or CNN. Pseudoenzyme
      overannotation is supported; prediction-time sequence identity and the native noncatalytic function
      remain unestablished.
    supported_by:
    - reference_id: file:DROME/CG43124/CG43124-bioinformatics/RESULTS.md
      supporting_text: 'CG43124 lacks two essential residues of the trypsin catalytic triad: the profile-aligned
        histidine is Ser69 and the aspartate is Asn112.'
    - reference_id: file:DROME/CG43124/CG43124-flybase.txt
      supporting_text: CG43124-PA FBpp0293647 28.4 245 8.18 A0A0B4K7P3 NP_001247345 AFH06662
    - reference_id: PMID:30367934
      supporting_text: 'The SP-related sequences in each species were divided into SPs or SPHs

        based on the presence or absence of the His-Asp-Ser catalytic triad'
references:
- id: PMID:30367934
  title: Building a platform for predicting functions of serine protease-related proteins in Drosophila
    melanogaster and other insects.
  findings:
  - statement: The genomic family study distinguishes serine proteases from noncatalytic homologs using
      catalytic-triad conservation; its methods support sequence-based classification, without providing
      a direct CG43124 biochemical assay.
    supporting_text: 'The SP-related sequences in each species were divided into SPs or SPHs

      based on the presence or absence of the His-Asp-Ser catalytic triad'
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PMID/title/DOI verified against PubMed and cached full text. Catalytic-triad classification
      methods read. The exact SPH249 supplementary-table row was not accessible and is not quoted or claimed
      as inspected.
- id: file:DROME/CG43124/CG43124-bioinformatics/RESULTS.md
  title: CG43124 exact-sequence catalytic-site analysis with positive control
  findings: []
- id: file:DROME/CG43124/CG43124-flybase.txt
  title: FlyBase FBgn0262587 CG43124 gene and single-polypeptide report
  findings: []
- id: file:DROME/CG43124/CG43124-protnlm-source.json
  title: Frozen ProtNLM2 release record for A0A0B4K7P3
  findings: []