id: A0A9L0JKX4
gene_symbol: TNFRSF1A
taxon:
  id: NCBITaxon:9793
  label: Equus asinus
status: COMPLETE
description: Assessment of 2 ProtNLM2 GO predictions for donkey TNFRSF1A (A0A9L0JKX4), the 410-aa
  product of an exon-3-skipping alternative Ensembl transcript of the TNFRSF1A gene; it is otherwise
  identical to the 453-aa canonical donkey product A0A8C4MD74. The skipped exon encodes the second half
  of cysteine-rich domain 1 and most of domain 2 (human residues 64-106), while the signal peptide,
  transmembrane segment and death domain are retained. Membrane is correct but less precise than the
  plasma membrane, Golgi membrane and membrane raft annotations the gene already carries (LSP). Signal
  transduction is correct for the retained death-domain module and is already in GOA on this product
  (CNN). Both predictions are generic and avoid the ligand-binding claims that are uncertain for this
  truncated ectodomain. A PubMed search for equine or donkey TNFR1 found no study of this transcript
  variant. ProtNLM2 also emitted non-GO subcellular locations "Cell membrane", "Membrane" and "Golgi
  apparatus membrane" for this accession, which are not scored here.
source_documents:
- projects/PROTNLM_EVALUATION/donkey40/donkey40-predictions.tsv
- genes/EQUAS/TNFRSF1A/TNFRSF1A-uniprot.txt
- genes/EQUAS/TNFRSF1A/TNFRSF1A-goa.tsv
- genes/EQUAS/TNFRSF1A/TNFRSF1A-bioinformatics/human_P19438-uniprot.txt
- genes/EQUAS/TNFRSF1A/TNFRSF1A-bioinformatics/RESULTS.md
- genes/EQUAS/TNFRSF1A/TNFRSF1A-bioinformatics/RESULTS-rereview.md
- genes/EQUAS/TNFRSF1A/TNFRSF1A-ai-review.yaml
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0016020
    label: membrane
  predicted_term_type: GO_CC
  review:
    assessment: LSP
    confidence_score: 2
    summary: The donkey model keeps the signal peptide and a single transmembrane segment
      (172-194), and human TNFR1 is a single-pass type I cell-membrane and Golgi-membrane protein,
      so membrane is correct. GOA for this product carries membrane raft (kept as non-core in the
      gene review), and the canonical product A0A8C4MD74 of the same gene carries plasma membrane
      (accepted in its review) and Golgi membrane; all are GO descendants of membrane, so the
      prediction is correct but less precise than existing annotations.
    supported_by:
    - reference_id: file:EQUAS/TNFRSF1A/TNFRSF1A-bioinformatics/human_P19438-uniprot.txt
      supporting_text: |-
        Cell membrane {ECO:0000269|PubMed:22801493};
        CC       Single-pass type I membrane protein {ECO:0000269|PubMed:22801493}.
    - reference_id: file:EQUAS/TNFRSF1A/TNFRSF1A-uniprot.txt
      supporting_text: |-
        FT   TRANSMEM        172..194
        FT                   /note="Helical"
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0007165
    label: signal transduction
  predicted_term_type: GO_BP
  review:
    assessment: CNN
    confidence_score: 2
    summary: The cytoplasmic death domain (311-396) is retained and aligns without gaps to the human
      TNFR1 death domain, which nucleates TRADD recruitment and downstream NF-kappaB and apoptotic
      signalling. Signal transduction is therefore correct for this protein even though its
      ligand-binding ectodomain is internally truncated (exon 3 skipped). The exact term is already
      in GOA for this product (InterPro2GO from the death domain) and is accepted in the gene review;
      the more specific TNF-mediated signaling pathway row is UNDECIDED there because ligand binding
      is uncertain, so CNN rather than LSP is used.
    supported_by:
    - reference_id: file:EQUAS/TNFRSF1A/TNFRSF1A-bioinformatics/human_P19438-uniprot.txt
      supporting_text: |-
        The aggregated death domains provide a novel
        CC       molecular interface that interacts specifically with the death domain
        CC       of TRADD.
    - reference_id: file:EQUAS/TNFRSF1A/TNFRSF1A-bioinformatics/RESULTS-rereview.md
      supporting_text: 'The 410-aa transcript lacks exactly one exon of the canonical transcript: exon 3 (ENSEASE00005153555, 129 nt = 43 codons, in frame).'
    - reference_id: PMID:8565075
      supporting_text: TRADD is a TNFR1-associated signal transducer that is involved in activating both pathways.
references:
- id: file:EQUAS/TNFRSF1A/TNFRSF1A-bioinformatics/human_P19438-uniprot.txt
  title: UniProtKB Swiss-Prot record P19438 (human TNFRSF1A), fetched 2026-10-14
  findings: []
- id: file:EQUAS/TNFRSF1A/TNFRSF1A-uniprot.txt
  title: UniProtKB record A0A9L0JKX4 (donkey TNFRSF1A)
  findings: []
- id: file:EQUAS/TNFRSF1A/TNFRSF1A-bioinformatics/RESULTS.md
  title: 'TNFRSF1A: donkey-human sequence comparison'
  findings: []
- id: file:EQUAS/TNFRSF1A/TNFRSF1A-bioinformatics/RESULTS-rereview.md
  title: 'TNFRSF1A (donkey): comparison of the two gene models'
  findings: []
- id: PMID:8565075
  title: TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways.
  findings: []