id: A0A9L0IQA3 gene_symbol: FBXL20 taxon: id: NCBITaxon:9793 label: Equus asinus status: COMPLETE description: Assessment of 3 ProtNLM2 GO predictions for donkey FBXL20 (A0A9L0IQA3), an alternative-first-exon product that keeps the canonical F-box, LRR domain and CAAX tail. Donkey GOA has cytoplasm, SCF ubiquitin ligase complex and SCF-dependent proteasomal protein catabolism, and the gene review adds ubiquitin-like ligase-substrate adaptor activity. Protein phosphatase binding (PR55alpha/PPP2R2A, a PP2A regulatory subunit) and regulation of autophagy (FBXL20-mediated VPS34 degradation) are supported by experimental work on the human ortholog and are absent from donkey GOA (COR). Protein monoubiquitination is not supported, because the characterised FBXL20 substrates are polyubiquitinated and degraded, and monoubiquitination is only raised as an untested possibility (UNC). No non-GO ProtNLM2 outputs (function text or location) were emitted for this accession. source_documents: - projects/PROTNLM_EVALUATION/donkey40/donkey40-predictions.tsv - genes/EQUAS/FBXL20/FBXL20-goa.tsv - genes/EQUAS/FBXL20/FBXL20-ai-review.yaml - genes/human/FBXL20/FBXL20-uniprot.txt - genes/EQUAS/FBXL20/FBXL20-bioinformatics/RESULTS-rereview.md predictions: - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-10-14 predicted_term: id: GO:0019903 label: protein phosphatase binding predicted_term_type: GO_MF review: assessment: COR confidence_score: 2 summary: Human FBXL20 binds PR55alpha (PPP2R2A), a regulatory subunit of the PP2A serine/threonine phosphatase, in vitro and in cells, and promotes its ubiquitination and degradation (PMID:34731788). The donkey product shares the canonical 422-residue F-box/LRR/CAAX body with human FBXL20 (same PANTHER subfamily PTHR13318:SF47), so the substrate-binding LRR domain is intact. The binding is a substrate-recognition interaction, so the term is correct but less informative than the adaptor activity the gene review records. Neither donkey GOA nor the human and mouse orthologs carry a phosphatase-binding term (human has only generic protein binding by IPI), so the prediction is novel. supported_by: - reference_id: PMID:34731788 supporting_text: FBXL20 interacts with PR55α in vitro and in vivo - reference_id: file:EQUAS/FBXL20/FBXL20-bioinformatics/RESULTS-rereview.md supporting_text: Downstream of the motif, A0A9L0IQA3 has the same 422-residue length as the - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-10-14 predicted_term: id: GO:0006513 label: protein monoubiquitination predicted_term_type: GO_BP review: assessment: UNC confidence_score: 1 summary: Characterised SCF(FBXL20) substrates (RIM1 in mouse, VPS34 and PR55alpha in human) are ubiquitinated and degraded by the proteasome, which implies polyubiquitination. The only mention of monoubiquitination is the mouse SCRAPPER study stating that RIM1 monoubiquitination cannot be excluded, which was not tested. The term is neither validated nor refuted, and it is not in donkey GOA or the gene review. supported_by: - reference_id: PMID:17803915 supporting_text: At present we cannot exclude the possibility that monoubiquitination of RIM1 by SCRAPPER may also regulate RIM1 before RIM1 is polyubiquitinated and degraded by the proteasome. - reference_id: PMID:34731788 supporting_text: an F-box protein that serves as a substrate recognition component of the SCF (Skp1_Cul1_F-box) E3 ubiquitin ligase complexes that promote proteasomal degradation - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-10-14 predicted_term: id: GO:0010506 label: regulation of autophagy predicted_term_type: GO_BP review: assessment: COR confidence_score: 2 summary: In human cells FBXL20 knockdown induces autophagy flux and raises VPS34 and PtdIns3P, and DNA damage induces p53-dependent FBXL20 expression that drives SCF-mediated VPS34 degradation and inhibits autophagy (PMID:25593308). FBXL20 thus acts as a negative regulator of autophagy; negative regulation of autophagy would be the more precise term. Donkey GOA, the donkey gene review and the human and mouse orthologs carry no autophagy term, so the prediction is novel. Transfer rests on the shared FBXL20 subfamily and the intact F-box and LRR domains of the donkey product. supported_by: - reference_id: PMID:25593308 supporting_text: FBXL20 was identified in a genome-wide siRNA screen as a gene when its expression was knocked down, leading to the induction of autophagy flux and increases in the levels of PtdIns3P - reference_id: PMID:25593308 supporting_text: Taken together, these results suggest that FBXL20–SKP1–CUL1 regulates the levels of Vps34 and autophagy through a proteasomal pathway. - reference_id: PMID:33234069 supporting_text: Removal of Vps34 by Fbxl20-mediated ubiquitination leads to inhibition of autophagy. - reference_id: file:EQUAS/FBXL20/FBXL20-bioinformatics/RESULTS-rereview.md supporting_text: Downstream of the motif, A0A9L0IQA3 has the same 422-residue length as the references: - id: file:human/FBXL20/FBXL20-uniprot.txt title: UniProt record for human FBXL20 (Q96IG2) findings: [] - id: file:EQUAS/FBXL20/FBXL20-bioinformatics/RESULTS-rereview.md title: 'FBXL20 (donkey A0A9L0IQA3): N-terminal exon comparison (re-review, 2026-10-21)' findings: [] - id: PMID:34731788 title: p53/FBXL20 axis negatively regulates the protein stability of PR55α, a regulatory subunit of PP2A Ser/Thr phosphatase. findings: [] - id: PMID:25593308 title: FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation. findings: [] - id: PMID:17803915 title: SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release. findings: [] - id: PMID:33234069 title: 'The FBXL family of F-box proteins: variations on a theme.' findings: []