id: A0A9L0T7K6
gene_symbol: USP8
taxon:
  id: NCBITaxon:9796
  label: Equus caballus
status: COMPLETE
description: Assessment of 1 ProtNLM GO predictions for the selected horse USP8 protein, using mammalian
  experimental findings and an explicit comparison of the horse sequence.
source_documents:
- genes/human/USP8/USP8-uniprot.txt
- genes/HORSE/USP8/USP8-bioinformatics/RESULTS.md
- projects/PROTNLM_EVALUATION/mammal-benchmark/horse40-predictions.csv
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-09-08
  predicted_term:
    id: GO:0006511
    label: ubiquitin-dependent protein catabolic process
  predicted_term_type: GO_BP
  review:
    assessment: CNN
    confidence_score: 2
    summary: USP8 is a deubiquitinase, but deubiquitination is not incompatible with participation in
      ubiquitin-dependent protein catabolism. Human USP8 controls endosomal ubiquitin dynamics and cargo
      sorting, including EGFR degradation, with substrate-specific effects on stability. The horse USP
      catalytic region is conserved in a sequence with 91.82% identity over 99.46% of the human protein.
      The existing target GOA term is biologically defensible as pathway participation, not an assertion
      that USP8 is a protease that directly destroys ubiquitinated substrates. Training-set membership
      is unknown.
    supported_by:
    - reference_id: file:human/USP8/USP8-uniprot.txt
      supporting_text: 'CC   -!- FUNCTION: Hydrolase that can remove conjugated ubiquitin from proteins

        CC       and therefore plays an important regulatory role at the level of

        CC       protein turnover by preventing degradation. Converts both ''Lys-48'' an

        CC       ''Lys-63''-linked ubiquitin chains. Catalytic activity is enhanced in the

        CC       M phase. Involved in cell proliferation. Required to enter into S phase

        CC       in response to serum stimulation. May regulate T-cell anergy mediated

        CC       by RNF128 via the formation of a complex containing RNF128 and OTUB1.

        CC       Probably regulates the stability of STAM2 and RASGRF1. Regulates

        CC       endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early

        CC       endosomes, and maintenance of ESCRT-0 stability. The level of protein

        CC       ubiquitination on endosomes is essential for maintaining the morphology

        CC       of the organelle. Deubiquitinates EPS15 and controls tyrosine kinase

        CC       stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR

        CC       degradation and downstream MAPK signaling. Involved in acrosome

        CC       biogenesis through interaction with the spermatid ESCRT-0 complex and

        CC       microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1.

        CC       Deubiquitinates BACE1 which inhibits BACE1 lysosomal degradation and

        CC       modulates BACE-mediated APP cleavage and amyloid-beta formation

        CC       (PubMed:27302062). {ECO:0000269|PubMed:16520378,

        CC       ECO:0000269|PubMed:17711858, ECO:0000269|PubMed:18329369,

        CC       ECO:0000269|PubMed:27302062, ECO:0000269|PubMed:9628861}.'
    - reference_id: file:HORSE/USP8/USP8-bioinformatics/RESULTS.md
      supporting_text: The horse sequence A0A9L0T7K6 (1112 residues) aligns to human P40818 (1118 residues)
        with 91.82% identity across 1112 paired residues. Paired coverage is 99.46% of the human sequence
        and 100.0% of the horse sequence.
    - reference_id: PMID:9628861
      supporting_text: "We have identified and \ncharacterized a novel human ubiquitin isopeptidase, UBPY,\
        \ which both as a \nrecombinant protein and upon immunoprecipitation from cell extracts is able\
        \ to \ncleave linear or isopeptide-linked ubiquitin chains."
references:
- id: file:human/USP8/USP8-uniprot.txt
  title: UniProt record for human USP8
  findings: []
- id: file:HORSE/USP8/USP8-bioinformatics/RESULTS.md
  title: "USP8: horse\u2013human sequence comparison"
  findings: []
- id: PMID:9628861
  title: 'UBPY: a growth-regulated human ubiquitin isopeptidase.'
  findings: []