ProtNLM2 External predictions
View prediction review YAML · USP8-protnlm-predictions-review.yaml · Review status: COMPLETE
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 · genes/HORSE/USP8/USP8-bioinformatics/RESULTS-rereview.md · projects/PROTNLM_EVALUATION/mammal-benchmark/horse40-predictions.csv
Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.
UNC — Uncertain Review score: 1/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: The predicted term matches an existing electronic GOA annotation for this horse gene (UniRule-based IEA on this product and on F7BV54), but that overlap is not biological support, and the gene review marks the term as over-annotated. Scored for this exact product, the prediction rests on deubiquitinase activity, and whether this splice form has it is unresolved. A0A9L0T7K6 uses an alternative 3' terminal exon. It keeps the MIT and rhodanese-like regions and the catalytic Cys785 and His1066, but only 328 of the 333 USP-domain residues align, and the conserved C-terminal USP segment (human ...AAYILFYTSLGPRVTDVAT) is replaced by an unrelated tail (...AASFSLHFREISQS). No assay of this form exists, so it is unclear whether the truncated USP fold is catalytically competent. At the gene level the term is also uncertain. USP8 is a cysteine-type deubiquitinase whose effects on protein turnover depend on the substrate. It stabilizes Nrdp1 and STAM by removing ubiquitin, yet its knockdown inhibits degradation of stimulated EGFR and Met. Human curators captured these roles with regulatory terms (regulation of protein stability, negative regulation of lysosomal protein catabolic process) rather than GO:0006511, and no experimental annotation or PAINT node assigns GO:0006511 to USP8.
Supporting Evidence:
- file:human/USP8/USP8-uniprot.txt: "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}."
- file:HORSE/USP8/USP8-bioinformatics/RESULTS.md: "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."
- file:HORSE/USP8/USP8-bioinformatics/RESULTS-rereview.md: "USP 777-1109: 328/333 residues aligned"
- file:HORSE/USP8/USP8-bioinformatics/RESULTS-rereview.md: "Sites: human S718 -> horse S717, human C786 -> horse C785, human H1067 -> horse H1066"
- file:HORSE/USP8/USP8-bioinformatics/RESULTS-rereview.md: "C-terminus from human 1090: human DISVSSVKSSAAYILFYTSLGPRVTDVAT; horse DIAVSSVKSSAASFSLHFREISQS"
- PMID:16520378: "Degradation of acutely stimulated receptor tyrosine kinases, epidermal growth factor receptor and Met, is strongly inhibited in UBPY knockdown cells"
- PMID:15314180: "USP8 markedly enhanced the stability of Nrdp1, and a point mutant that disrupts USP8 catalytic activity destabilized endogenous Nrdp1."
- PMID:9628861: "We have identified and characterized a novel human ubiquitin isopeptidase, UBPY, which both as a recombinant protein and upon immunoprecipitation from cell extracts is able to cleave linear or isopeptide-linked ubiquitin chains."