id: A0A9L0JCH5
gene_symbol: USP36
taxon:
  id: NCBITaxon:9793
  label: Equus asinus
status: COMPLETE
description: 'Assessment of 1 ProtNLM2 GO prediction for donkey USP36 (A0A9L0JCH5), judged against the
  donkey GOA record (cysteine-type deubiquitinase activity, protein deubiquitination, protein stabilization,
  regulation of rRNA processing, nucleolus and others), the human ortholog Q9P275 and cached USP36 studies
  (PMID:19208757, PMID:25775507), and a donkey-human alignment (78% identity, catalytic Cys/His conserved).
  Ubiquitin-dependent protein catabolic process is present in donkey GOA only through a family-level
  UniRule, which the gene review marks as over-annotated; the characterized activity of USP36 protects
  its substrates from proteasomal degradation rather than carrying out a step of it, so the prediction
  is refuted (NPI). Non-GO ProtNLM2 outputs, not scored: subcellular locations ''Cytoplasm'' and
  ''Nucleus'' (both consistent with human data, though they omit the principal nucleolar location) and
  function text ''Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate
  different cellular processes'', which is a correct but generic USP-family statement.'
source_documents:
- projects/PROTNLM_EVALUATION/donkey40/donkey40-predictions.tsv
- genes/EQUAS/USP36/USP36-goa.tsv
- genes/EQUAS/USP36/USP36-bioinformatics/human-Q9P275-uniprot.txt
- genes/EQUAS/USP36/USP36-bioinformatics/RESULTS.md
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  predicted_term_type: GO_BP
  review:
    assessment: NPI
    error_type: FREQUENCY_BIAS
    confidence_score: 0
    summary: The term is already in donkey GOA, but only via a family-wide UniRule (GO_REF:0000104) applied
      to peptidase C19 members, so the overlap does not establish correctness and the prediction is not
      novel. Donkey USP36 sits in PANTHER subfamily PTHR24006:SF653 (ubiquitin carboxyl-terminal hydrolase
      36) with its catalytic Cys/His conserved, so the human ortholog's characterized activity transfers.
      That activity runs against the predicted process. Human USP36 deubiquitinates nucleophosmin, fibrillarin
      and c-Myc and thereby stabilizes them against proteasomal degradation (PMID:19208757, PMID:25775507),
      and PubMed searches for USP36 with degradation or proteasome return substrate-stabilization reports
      only, with no report of USP36 acting in a step of ubiquitin-dependent catabolism such as proteasome-associated
      chain trimming. The re-reviewed gene review marks the GOA row for this term as over-annotated on these
      grounds, which refute the prediction. ProtNLM2 repeats the generic DUB-family process label rather
      than the protein's substrate-protective role (protein stabilization).
    supported_by:
    - reference_id: PMID:19208757
      supporting_text: USP36 deubiquitylated the nucleolar proteins nucleophosmin/B23 and fibrillarin, and
        stabilized them by counteracting ubiquitylation-mediated proteasomal degradation
    - reference_id: PMID:25775507
      supporting_text: USP36 interacts with and deubiquitinates c-Myc in cells and in vitro, leading to
        the stabilization of c-Myc
    - reference_id: file:EQUAS/USP36/USP36-bioinformatics/RESULTS.md
      supporting_text: The catalytic nucleophile (donkey Cys131 = human Cys131) and proton acceptor (donkey
        His415 = human His382) of the USP domain are conserved.
references:
- id: file:EQUAS/USP36/USP36-goa.tsv
  title: Donkey USP36 GOA annotations
  findings: []
- id: file:EQUAS/USP36/USP36-bioinformatics/human-Q9P275-uniprot.txt
  title: UniProt record for human USP36 (Q9P275)
  findings: []
- id: file:EQUAS/USP36/USP36-bioinformatics/RESULTS.md
  title: 'USP36: donkey-human sequence comparison'
  findings: []
- id: PMID:19208757
  title: Nucleolar structure and function are regulated by the deubiquitylating enzyme USP36.
  findings: []
- id: PMID:25775507
  title: The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c-Myc.
  findings: []