id: A0A9L0JJJ9
gene_symbol: APP
taxon:
  id: NCBITaxon:9793
  label: Equus asinus
status: COMPLETE
description: 'Assessment of 3 ProtNLM2 GO predictions for donkey APP (A0A9L0JJJ9). Extracellular region
  is already in donkey GOA and correct (CNN). Nucleus is in donkey GOA and correct only for the AICD/gamma-CTF
  fragment (CNN). Apoptotic process is supported by the pro-apoptotic activity of the caspase-derived C31
  peptide and the gamma-secretase-released intracellular domain of human APP, whose sequence donkey
  shares, and no apoptosis term is in donkey GOA (COR). Non-GO ProtNLM2 output, not scored: subcellular location ''Endosome'',
  which matches the experimentally established endosomal trafficking of human APP.'
source_documents:
- projects/PROTNLM_EVALUATION/donkey40/donkey40-predictions.tsv
- genes/EQUAS/APP/APP-goa.tsv
- genes/human/APP/APP-uniprot.txt
- genes/EQUAS/APP/APP-bioinformatics/RESULTS.md
- genes/EQUAS/APP/APP-bioinformatics/ortholog_experimental_goa.txt
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0006915
    label: apoptotic process
  predicted_term_type: GO_BP
  review:
    assessment: COR
    confidence_score: 2
    summary: Caspase cleavage of human APP releases the C31 peptide, a potent inducer of apoptosis (PMID:10742146),
      and the gamma-secretase-released intracellular domain acts as a positive regulator of apoptosis (PMID:12214090);
      Swiss-Prot summarizes both as enhancers of neuronal apoptosis. The donkey intracellular domain, including
      the caspase site region and YENPTY motif, is identical to human, so the transfer is justified within
      the APP orthology group. No apoptosis term of any kind is in the donkey GOA record or the donkey gene
      review (human APP carries apoptotic process as an accepted IEA), so the prediction is novel for this
      gene. The role is fragment-mediated and non-core, and the evidence is for induction rather than execution,
      so positive regulation of neuron apoptotic process would be the more precise term.
    supported_by:
    - reference_id: file:human/APP/APP-uniprot.txt
      supporting_text: peptides, including C31, are potent enhancers of neuronal apoptosis.
    - reference_id: PMID:10742146
      supporting_text: The resultant C31 peptide was a potent inducer of apoptosis.
    - reference_id: PMID:12214090
      supporting_text: demonstrate that AID acts as a positive regulator of apoptosis
    - reference_id: file:EQUAS/APP/APP-bioinformatics/RESULTS.md
      supporting_text: transmembrane region and intracellular domain (700-770) identical, including the
        YENPTY motif
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0005576
    label: extracellular region
  predicted_term_type: GO_CC
  review:
    assessment: CNN
    confidence_score: 2
    summary: After alpha-secretase cleavage the soluble APP ectodomain is released into the extracellular
      space and amyloid-beta is secreted; human APP has IDA support for the extracellular region. The
      exact term is already in donkey GOA (combined IEA). Correct but not novel.
    supported_by:
    - reference_id: file:human/APP/APP-uniprot.txt
      supporting_text: APP is released into the extracellular space and the C-terminal is
    - reference_id: file:EQUAS/APP/APP-bioinformatics/ortholog_experimental_goa.txt
      supporting_text: P05067 APP is_active_in GO:0005576 "extracellular region" IDA PMID:29518356
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0005634
    label: nucleus
  predicted_term_type: GO_CC
  review:
    assessment: CNN
    confidence_score: 2
    summary: The gamma-secretase-released C-terminal fragment (AICD) is located in both cytoplasm and
      nucleus of neurons (human EXP, PMID:11544248). The exact term is already in donkey GOA. Correct
      for a fragment of the gene product, though not for full-length APP; not novel.
    supported_by:
    - reference_id: file:human/APP/APP-uniprot.txt
      supporting_text: Located to both the cytoplasm and nuclei of neurons.
    - reference_id: file:EQUAS/APP/APP-bioinformatics/ortholog_experimental_goa.txt
      supporting_text: P05067 APP located_in GO:0005634 "nucleus" EXP PMID:11544248
references:
- id: PMID:10742146
  title: A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor.
  findings: []
- id: PMID:12214090
  title: Generation of an apoptotic intracellular peptide by gamma-secretase cleavage of Alzheimer's amyloid
    beta protein precursor.
  findings: []
- id: file:human/APP/APP-uniprot.txt
  title: UniProt record for human APP (P05067)
  findings: []
- id: file:EQUAS/APP/APP-bioinformatics/RESULTS.md
  title: 'APP: donkey-human sequence comparison'
  findings: []
- id: file:EQUAS/APP/APP-bioinformatics/ortholog_experimental_goa.txt
  title: Experimental GO annotations of human, mouse and rat APP orthologs (QuickGO)
  findings: []