id: A0A9L0JQ61
gene_symbol: PIKFYVE
taxon:
  id: NCBITaxon:9793
  label: Equus asinus
status: COMPLETE
description: >-
  Assessment of the single ProtNLM2 GO prediction for donkey PIKFYVE entry A0A9L0JQ61 (DONKEY40 cohort).
  The 460-residue input is a non-canonical splice product of the donkey PIKFYVE gene (canonical product
  A0A8C4L106), not the full-length phosphoinositide kinase: alignment shows it is the counterpart
  of the short human PIKFYVE splice isoform 3 (96.08% identity), lacking the PIPK catalytic domain, the
  chaperonin-like domain and most of the FYVE finger, while retaining the DEP domain. The predicted
  phosphatidylinositol phosphate biosynthetic process transfers the full-length enzyme's catalytic output
  (the ProtNLM2 evidence record cites a phmmer match to full-length mouse Pikfyve Q9Z1T6) to a protein that
  cannot catalyze it; because a non-catalytic contribution through the retained DEP-containing region is neither shown nor excluded, it is scored UNC. Non-GO ProtNLM2 output for this
  accession, not scored here: subcellular location "Nucleus", whose evidence record is a weak phmmer match
  (score 26.2) to Drosophila Dishevelled (P51140), a DEP-domain protein; full-length PIKFYVE is an endosomal
  membrane protein, and no data place the short isoform in the nucleus. No function text was emitted.
source_documents:
- projects/PROTNLM_EVALUATION/donkey40/donkey40-predictions.tsv
- projects/PROTNLM_EVALUATION/donkey40/donkey40-evidence.tsv
- genes/EQUAS/PIKFYVE/PIKFYVE-goa.tsv
- genes/EQUAS/PIKFYVE/PIKFYVE-bioinformatics/RESULTS.md
- genes/EQUAS/PIKFYVE/PIKFYVE-bioinformatics/human-Q9Y2I7-uniprot.txt
- genes/EQUAS/PIKFYVE/PIKFYVE-ai-review.yaml
- genes/EQUAS/PIKFYVE__A0A8C4L106/PIKFYVE__A0A8C4L106-goa.tsv
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0046854
    label: phosphatidylinositol phosphate biosynthetic process
  predicted_term_type: GO_BP
  review:
    assessment: UNC
    confidence_score: 1
    summary: Full-length PIKFYVE contributes to phosphatidylinositol phosphate biosynthesis by synthesizing
      PtdIns(3,5)P2 and PtdIns5P through its C-terminal PIPK domain. The selected donkey protein is the
      product of a non-canonical transcript corresponding to human isoform 3, which ends at residue 548 and
      contains no part of the PIPK domain (human 1758-2084), so it cannot perform the catalytic step. That
      excludes the gene's main mode of participation, but it does not exclude every other mode. The short
      product also lacks the Cpn60_TCP1 (chaperonin-like) domain, which the PAS-complex study identifies as
      a major, not the sole, determinant of ArPIKfyve(VAC14)-Sac3(FIG4) association, and it lacks the complete
      FYVE finger that targets the enzyme to endosomes. It retains the N-terminal region and the DEP domain
      (donkey 277-352), whose contribution to the PAS complex or to lipid synthesis has been neither shown
      nor excluded. No study characterizes the short isoform, and endogenous human PIKfyve was detected as a
      single molecular species, so a binding or regulatory contribution is unsupported but not refuted. The
      prediction most likely transfers the full-length enzyme's output through the shared N-terminal and DEP
      region, and the term cannot be validated or refuted for this product, so it is scored UNC. At the gene
      level the claim is not novel, because the canonical donkey product A0A8C4L106 already carries
      phosphatidylinositol metabolic process and PI(3,5)P2 metabolic process annotations.
    supported_by:
    - reference_id: file:EQUAS/PIKFYVE/PIKFYVE-bioinformatics/human-Q9Y2I7-uniprot.txt
      supporting_text: 'CC       catalyze the phosphorylation of phosphatidylinositol 3-phosphate on the'
    - reference_id: file:EQUAS/PIKFYVE/PIKFYVE-bioinformatics/human-Q9Y2I7-uniprot.txt
      supporting_text: 'FT   DOMAIN          1758..2084'
    - reference_id: file:EQUAS/PIKFYVE/PIKFYVE-bioinformatics/human-Q9Y2I7-uniprot.txt
      supporting_text: 'FT                   /note="Missing (in isoform 2, isoform 3 and isoform 4)"'
    - reference_id: file:EQUAS/PIKFYVE/PIKFYVE-bioinformatics/RESULTS.md
      supporting_text: It also lacks the chaperonin-like domain (human 616-868) and the entire PIPK catalytic
        domain (human 1758-2084).
    - reference_id: file:EQUAS/PIKFYVE/PIKFYVE-bioinformatics/RESULTS.md
      supporting_text: The donkey sequence aligns to human isoform Q9Y2I7-3 (462 residues) with 96.08% identity
        among 459 paired residues
    - reference_id: PMID:19840946
      supporting_text: We identified the Cpn60_TCP1 domain of PIKfyve as a major determinant for associating
        the ArPIKfyve-Sac3 subcomplex.
    - reference_id: PMID:16448788
      supporting_text: PIKfyve is expressed as a single molecular species in a number of human cell lines
        derived from different tissues.
references:
- id: file:EQUAS/PIKFYVE/PIKFYVE-bioinformatics/RESULTS.md
  title: 'PIKFYVE: donkey A0A9L0JQ61 versus human PIKFYVE isoforms'
  findings: []
- id: file:EQUAS/PIKFYVE/PIKFYVE-bioinformatics/human-Q9Y2I7-uniprot.txt
  title: UniProtKB/Swiss-Prot record Q9Y2I7 (human PIKFYVE), downloaded 2026-10-14
  findings: []
- id: PMID:19840946
  title: 'PIKfyve-ArPIKfyve-Sac3 core complex: contact sites and their consequence for Sac3 phosphatase
    activity and endocytic membrane homeostasis.'
  findings: []
- id: PMID:16448788
  title: Cloning and subcellular localization of a human phosphatidylinositol 3-phosphate 5-kinase, PIKfyve/Fab1.
  findings: []