id: A0A8C4LTV9
gene_symbol: PDIA4
taxon:
  id: NCBITaxon:9793
  label: Equus asinus
status: COMPLETE
description: Assessment of the single ProtNLM2 GO prediction for donkey PDIA4 (A0A8C4LTV9). The UniProt
  entry is a 1197-aa merged gene model in which a KRAB domain and ten C2H2 zinc fingers most similar to
  human ZNF786 (the gene immediately upstream of PDIA4 in human) precede a complete PDIA4 (ERp72) protein
  disulfide isomerase lacking its signal peptide. The predicted double-stranded DNA binding derives from
  the zinc-finger segment and does not describe PDIA4, an ER luminal oxidoreductase (NPI, WRONG_INPUT_SEQUENCE);
  the gene review removes the other zinc-finger-derived annotations (nucleus, regulation of DNA-templated
  transcription) on the same grounds, and a PubMed search for PDIA4/ERp72 and DNA binding returned no
  report of DNA binding by PDIA4. ProtNLM2 also emitted function text (not scored) - "Participates in
  the folding of proteins containing disulfide bonds, may be involved in glycosylation, prolyl hydroxylation
  and triglyceride transfer" - whose first clause fits PDIA4; the remaining clauses resemble descriptions
  of canonical PDI (P4HB) and are not established for PDIA4 (the evidence key for this text is a phmmer
  match to alfalfa PDI, P29828). No location was emitted.
source_documents:
- projects/PROTNLM_EVALUATION/donkey40/donkey40-predictions.tsv
- projects/PROTNLM_EVALUATION/donkey40/donkey40-evidence.tsv
- genes/EQUAS/PDIA4/PDIA4-goa.tsv
- genes/EQUAS/PDIA4/PDIA4-uniprot.txt
- genes/EQUAS/PDIA4/PDIA4-bioinformatics/RESULTS.md
- genes/EQUAS/PDIA4/PDIA4-bioinformatics/ALT_ENTRY.md
- genes/EQUAS/PDIA4/PDIA4-bioinformatics/RESULTS-rereview.md
- genes/EQUAS/PDIA4/PDIA4-ai-review.yaml
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0003690
    label: double-stranded DNA binding
  predicted_term_type: GO_MF
  review:
    assessment: NPI
    confidence_score: 0
    error_type: WRONG_INPUT_SEQUENCE
    summary: The input sequence fuses a KRAB-C2H2 zinc-finger segment (residues 1 to about 580, 64% identical
      to human ZNF786) to PDIA4;
      the ProtNLM2 evidence for this GO term is a weak phmmer match to mouse zinc finger protein 148 (Q61624),
      i.e. the zinc-finger part. Human PDIA4 is a 645-aa ER luminal disulfide isomerase with no zinc-finger
      region, the PDIA4 part of the donkey entry aligns to human residues 17-645, and the signal peptide
      needed for ER entry is missing, which together indicate a gene-model fusion rather than a real PDIA4
      protein. A second donkey entry from the same Ensembl gene shows the same KRAB-type N-terminus. DNA
      binding is not a PDIA4 function (ERp72 is an abundant ER luminal protein), so the prediction is incorrect for this gene; the cause is the
      chimeric input sequence, not paralog confusion.
    supported_by:
    - reference_id: file:EQUAS/PDIA4/PDIA4-uniprot.txt
      supporting_text: InterPro; IPR001909; KRAB.
    - reference_id: file:EQUAS/PDIA4/PDIA4-bioinformatics/RESULTS-rereview.md
      supporting_text: 'N-terminal segment vs human ZNF786 (Q8N393, 782 aa): 64.2% identity over 565 paired residues;
        donkey 1-580, human 1-649'
    - reference_id: file:EQUAS/PDIA4/PDIA4-bioinformatics/ALT_ENTRY.md
      supporting_text: A0A8C4LTV9 (1197 aa) residues 571-1197 align locally to P13667 (645 aa) residues
        17-645
    - reference_id: file:EQUAS/PDIA4/PDIA4-bioinformatics/human-P13667-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen'
    - reference_id: PMID:2295602
      supporting_text: two abundant, luminal endoplasmic reticulum proteins (ERp), ERp59/PDI and ERp72
references:
- id: file:EQUAS/PDIA4/PDIA4-uniprot.txt
  title: UniProt record for donkey PDIA4 (A0A8C4LTV9)
  findings: []
- id: file:EQUAS/PDIA4/PDIA4-bioinformatics/ALT_ENTRY.md
  title: 'PDIA4: the two donkey PDIA4 UniProt entries'
  findings: []
- id: file:EQUAS/PDIA4/PDIA4-bioinformatics/human-P13667-uniprot.txt
  title: UniProt record for human PDIA4 (P13667)
  findings: []
- id: file:EQUAS/PDIA4/PDIA4-bioinformatics/RESULTS-rereview.md
  title: 'PDIA4 re-review: locus context and N-terminal segment identity'
  findings: []
- id: PMID:2295602
  title: ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site
    sequences of protein disulfide isomerase.
  findings: []