id: A0A0B4LFV5
gene_symbol: CG33453
taxon:
  id: NCBITaxon:7227
  label: Drosophila melanogaster
status: COMPLETE
description: Enzyme activation remains unverified for this DUF1091 protein. Transfer of the mammalian
  ganglioside-catabolism pathway is contradicted by the native fly glycolipid context.
source_documents:
- genes/DROME/CG33453/CG33453-protnlm-source.json
- genes/DROME/CG33453/CG33453-flybase.txt
- genes/DROME/CG33453/CG33453-uniprot.txt
- genes/DROME/CG33453/CG33453-donor-P17900-uniprot.txt
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-08
  source_reference_id: file:DROME/CG33453/CG33453-protnlm-source.json
  predicted_term:
    id: GO:0008047
    label: enzyme activator activity
  predicted_term_type: GO_MF
  review:
    assessment: UNC
    confidence_score: 1
    summary: The source reports structural matches to macaque GM2 activator Q8HXX6, with TM-align scores
      approximately 0.59/0.55. Current target annotations identify DUF1091, not an experimentally established
      GM2-activator mechanism. A structurally similar secreted fold could bind lipids or proteins, but
      the exact claim requires evidence of direct stimulation of a defined enzyme. No target enzyme, activation
      assay or justified conserved interaction has been demonstrated for CG33453; secretion and a donor
      annotation alone are insufficient. No equivalent positive target annotation exists.
    supported_by:
    - &id001
      reference_id: file:DROME/CG33453/CG33453-flybase.txt
      supporting_text: CG33453-PB FBpp0309413 20.1 174 9.64 A0A0B4LFV5 NP_001286610 AHN56405
    - reference_id: file:DROME/CG33453/CG33453-uniprot.txt
      supporting_text: DR   InterPro; IPR010512; DUF1091.
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-08
  source_reference_id: file:DROME/CG33453/CG33453-protnlm-source.json
  predicted_term:
    id: GO:0006689
    label: ganglioside catabolic process
  predicted_term_type: GO_BP
  review:
    assessment: NPI
    confidence_score: 0
    summary: The structural donor for this prediction is human GM2 activator P17900. That protein presents
      ganglioside GM2 for lysosomal hydrolysis, a substrate-specific pathway that cannot be transferred
      solely from a moderate fold match. Primary lipid-analysis and transgenic-reconstitution work shows
      that gangliosides are not intrinsically detectable in ordinary Drosophila and must be induced using
      introduced synthesis enzymes and supplied precursor. This contradicts assignment of an endogenous
      ganglioside-catabolism role to native CG33453. It does not claim that flies cannot sialylate glycoproteins
      or that an engineered/exogenous substrate could never be degraded. No equivalent positive target
      annotation exists.
    supported_by:
    - reference_id: PMID:29844375
      supporting_text: 'In insects, including

        the fruit fly Drosophila melanogaster, gangliosides are not intrinsically

        present at a detectable level.'
    - reference_id: file:DROME/CG33453/CG33453-donor-P17900-uniprot.txt
      supporting_text: degradation of ganglioside GM2. Extracts single GM2 molecules from
    - *id001
    error_type: PATHWAY_CONTEXT_IGNORED
references:
- id: file:DROME/CG33453/CG33453-flybase.txt
  title: CG33453-flybase.txt
  findings: []
- id: file:DROME/CG33453/CG33453-uniprot.txt
  title: CG33453-uniprot.txt
  findings: []
- id: PMID:29844375
  title: Induction of ganglioside synthesis in Drosophila brain accelerates assembly of amyloid β protein.
  findings: []
- id: file:DROME/CG33453/CG33453-donor-P17900-uniprot.txt
  title: CG33453-donor-P17900-uniprot.txt
  findings: []