id: A0A9L0J2B1
gene_symbol: GPC3
taxon:
  id: NCBITaxon:9793
  label: Equus asinus
status: COMPLETE
description: Assessment of the single ProtNLM2 GO prediction for donkey GPC3 entry A0A9L0J2B1, an alternative-first-exon
  gene model of the GPI-anchored heparan sulfate proteoglycan GPC3 that lacks the signal peptide of the canonical
  product (A0A9L0JGR2). The prediction regulation of signal transduction (GO:0009966) is true of the gene. A rule-based
  hydropathy and n/h/c-region analysis finds no classical secretory signal in the alternative N-terminus, so the
  known cell-surface mechanism is unlikely to be available to this product, but the analysis is not a trained predictor
  and other contributions are neither shown nor excluded; the prediction is scored UNC. ProtNLM2 emitted no function
  text or subcellular location for this accession.
source_documents:
- projects/PROTNLM_EVALUATION/donkey40/donkey40-predictions.tsv
- projects/PROTNLM_EVALUATION/donkey40/donkey40-evidence.tsv
- genes/EQUAS/GPC3/GPC3-uniprot.txt
- genes/EQUAS/GPC3/GPC3-goa.tsv
- genes/EQUAS/GPC3/GPC3-bioinformatics/human-GPC3-P51654-uniprot.txt
- genes/EQUAS/GPC3/GPC3-bioinformatics/RESULTS.md
- genes/EQUAS/GPC3/GPC3-bioinformatics/RESULTS-rereview.md
- genes/EQUAS/GPC3/GPC3-bioinformatics/signal_peptide_hydropathy_output.txt
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0009966
    label: regulation of signal transduction
  predicted_term_type: GO_BP
  review:
    assessment: UNC
    confidence_score: 1
    summary: GPC3 regulates Wnt and hedgehog signaling as a GPI-anchored heparan sulfate proteoglycan at the
      cell surface; human GPC3 stimulates canonical Wnt signaling by binding Frizzled through its heparan sulfate
      chains. That mechanism needs entry into the secretory pathway, where the GPI anchor and heparan sulfate
      chains are added. A0A9L0J2B1 is an alternative-first-exon gene model whose first 43 residues are not
      homologous to the human N-terminus and lack the human signal peptide (P51654 SIGNAL 1..24). A Kyte-Doolittle
      and von Heijne-style n/h/c-region scan (signal_peptide_hydropathy.py) recovers the signal peptide and its
      cleavage after residue 24 in both human P51654 and the canonical donkey product A0A9L0JGR2, but finds no
      candidate h-region in A0A9L0J2B1; its most hydrophobic 7-residue window has a mean of 1.54, against 3.36
      in the controls, and its longest apolar run is 5 residues. This is evidence against a classical secretory
      signal, so the known cell-surface mechanism is probably unavailable to this product. It is not positive
      refutation of the process term, however. The scan is a rule-based check rather than a trained predictor,
      the transcript itself is unconfirmed, and a contribution to signal regulation by the retained core protein
      through some other route is neither shown nor excluded. The call is therefore uncertain. The term is
      true of the GPC3 gene through its canonical product A0A9L0JGR2; donkey GOA already carries it and the
      more specific positive regulation of canonical Wnt signaling pathway (GO:0090263), so the prediction
      is not novel at the gene level.
    supported_by:
    - reference_id: file:EQUAS/GPC3/GPC3-bioinformatics/signal_peptide_hydropathy_output.txt
      supporting_text: 'Signal peptide (n/h/c rule): FOUND, h 7..14, predicted cleavage after 24 (MAGTVRTACLVVAMLLSLDFPGQA)'
    - reference_id: file:EQUAS/GPC3/GPC3-bioinformatics/signal_peptide_hydropathy_output.txt
      supporting_text: 'Max Kyte-Doolittle mean, window 7: 1.54 at residues 19..25'
    - reference_id: file:EQUAS/GPC3/GPC3-bioinformatics/signal_peptide_hydropathy_output.txt
      supporting_text: 'Longest apolar run: 5 residues at 21..25 (MVMMM)'
    - reference_id: file:EQUAS/GPC3/GPC3-bioinformatics/RESULTS-rereview.md
      supporting_text: 'Human signal peptide present verbatim in donkey: False'
    - reference_id: file:EQUAS/GPC3/GPC3-bioinformatics/RESULTS-rereview.md
      supporting_text: Its first 43 residues are not homologous to the human signal peptide/N-terminal region
    - reference_id: PMID:24496449
      supporting_text: GPC3 stimulates HCC growth by promoting canonical Wnt signaling.
    - reference_id: file:EQUAS/GPC3/GPC3-bioinformatics/human-GPC3-P51654-uniprot.txt
      supporting_text: Positively regulates the canonical Wnt signaling pathway by binding to
references:
- id: PMID:24496449
  title: Glypican-3 binds to Frizzled and plays a direct role in the stimulation of canonical Wnt signaling.
  findings: []
- id: file:EQUAS/GPC3/GPC3-bioinformatics/human-GPC3-P51654-uniprot.txt
  title: UniProt record for human GPC3 (P51654)
  findings: []
- id: file:EQUAS/GPC3/GPC3-bioinformatics/RESULTS-rereview.md
  title: 'GPC3 (donkey A0A9L0J2B1): N-terminal gene-model check'
  findings: []
- id: file:EQUAS/GPC3/GPC3-bioinformatics/signal_peptide_hydropathy_output.txt
  title: 'GPC3 (donkey A0A9L0J2B1): Kyte-Doolittle and n/h/c-region signal-peptide scan'
  findings: []