| Category | Specific finding | Evidence type (primary, review, database, figure) | Publication (authors/year/journal) | URL/DOI | Key notes |
|---|---|---|---|---|---|
| Identity/domains/localization | UniProt Q9UKT4 matches human FBXO5 or EMI1; Emi1 is a somatic APC/C inhibitor, largely nuclear in interphase, and figure evidence supports an N-terminal F-box plus C-terminal D-box and ZBR architecture. | Primary, figure | Miller et al., 2006, Genes and Development | https://doi.org/10.1101/gad.1454006 | Identity aligns with user-supplied UniProt entry and literature synonymy FBXO5 equals EMI1; figure schematic shows F-box, D-box, and ZBR; nuclear APC/C association described (pqac-00000003, pqac-00000024, pqac-00000025) |
| Identity/domains/localization | Human Emi1 or FBXO5 is described as the somatic paralogue in the Emi family; the ZBR domain is recognized in Emi1, supporting the UniProt domain assignment. | Primary | Shoji et al., 2014, FEBS Open Bio | https://doi.org/10.1016/j.fob.2014.06.010 | Supports domain and family alignment and correct human-gene identity (pqac-00000007, pqac-00000016) |
| Core molecular function | FBXO5 or EMI1 inhibits APC/C, especially APC/C with CDH1, as a high-affinity pseudosubstrate inhibitor required in interphase to permit cyclin accumulation and mitotic entry. | Primary | Miller et al., 2006, Genes and Development | https://doi.org/10.1101/gad.1454006 | Emi1 binds tightly to APC/C and Cdh1 and prevents premature APC/C activity during S and G2 (pqac-00000001, pqac-00000009, pqac-00000010) |
| Core molecular function | The Emi1 D-box mediates high-affinity docking to the APC/C D-box receptor, while the ZBR provides a second inhibitory activity that blocks APC/C function and prevents Emi1 from becoming a normal APC/C substrate. | Primary | Miller et al., 2006, Genes and Development | https://doi.org/10.1101/gad.1454006 | Mutation of the ZBR converts Emi1 into a D-box-dependent APC/C substrate; both D-box and ZBR are needed for full inhibition (pqac-00000002, pqac-00000008, pqac-00000011) |
| Key interactors/complexes | EMI1 physically associates with APC/C core subunits and coactivator Cdh1 in large nuclear complexes; reported APC/C partners include APC1, APC3 or Cdc27, APC4, APC5, APC6 or Cdc16, APC7, APC8 or Cdc23, and APC11. | Primary | Miller et al., 2006, Genes and Development | https://doi.org/10.1101/gad.1454006 | Establishes pathway placement and direct biochemical interaction with APC/C machinery (pqac-00000003, pqac-00000009) |
| Key interactors/complexes | Beyond APC/C inhibition, EMI1 is also described as an F-box protein capable of serving as the variable substrate receptor in an SCF EMI1 complex, with RAD51 cited as a substrate. | Primary | Gudino et al., 2024, British Journal of Cancer | https://doi.org/10.1038/s41416-024-02855-9 | Important nuance: FBXO5 has both a canonical F-box family identity and a better-established role as APC/C inhibitor; SCF adaptor role is noted in this recent paper (pqac-00000014, pqac-00000034) |
| Regulation/turnover | EMI1 is destroyed at mitotic entry through a PLK1-dependent SCF beta TrCP or TrCP pathway, relieving APC/C inhibition and enabling degradation of cyclins A and B. | Primary | Miller et al., 2006, Genes and Development | https://doi.org/10.1101/gad.1454006 | Classic turnover mechanism linking kinase signaling to ubiquitin-mediated release of APC/C inhibition (pqac-00000009, pqac-00000015) |
| Regulation/turnover | APC/C with CDH1 can also reduce Emi1 levels under some experimental conditions, particularly when ZBR-dependent protection is lost, indicating Emi1 inhibitory domains normally protect it from APC/C-mediated ubiquitination. | Primary | Miller et al., 2006, Genes and Development | https://doi.org/10.1101/gad.1454006 | Helps explain why ZBR mutation shifts Emi1 from inhibitor to APC/C substrate (pqac-00000008) |
| Recent 2023-2024 developments | In breast cancer, METTL16 stabilizes FBXO5 mRNA through m6A modification; METTL16 knockdown lowers FBXO5 and suppresses proliferation, migration, invasion, epithelial to mesenchymal transition, tumor growth, and lung metastasis. | Primary | Wang et al., 2024, Cancer and Metabolism | https://doi.org/10.1186/s40170-024-00351-5 | Positions FBXO5 as an epitranscriptomically regulated oncogenic effector and potential therapeutic target (pqac-00000006, pqac-00000031) |
| Recent 2023-2024 developments | In lung adenocarcinoma, PTBP1 controls FBXO5 splicing; PTBP1 knockdown promotes exon 3 skipping to generate an unstable FBXO5-S isoform, decreasing total FBXO5 and promoting cellular senescence. | Primary | Li et al., 2024, Current Issues in Molecular Biology | https://doi.org/10.3390/cimb46070458 | Suggests a PTBP1 to FBXO5 splicing to senescence axis with translational relevance for cancer biology (pqac-00000028, pqac-00000033) |
| Recent 2023-2024 developments | Reduced EMI1 expression in colonic epithelial models increases chromosome instability, DNA damage, and transformation phenotypes, supporting a role for EMI1 loss in early colorectal tumorigenesis. | Primary | Gudino et al., 2024, British Journal of Cancer | https://doi.org/10.1038/s41416-024-02855-9 | Important counterpoint to EMI1 as purely oncogenic: insufficient EMI1 can destabilize chromosomes and promote transformation (pqac-00000026, pqac-00000034) |
| Recent 2023-2024 developments | Quantitative proteomics in 2024 highlighted a broad PLK1-dependent G2 to M degradation program mediated partly by SCF beta TrCP, reinforcing the established mitotic-degradation axis relevant to EMI1 turnover. | Primary | Mouery et al., 2024, Cell Reports | https://doi.org/10.1016/j.celrep.2024.114510 | The paper notes FBXO5 or EMI1 among proteins whose mitotic degradation had previously been shown to be PLK1 dependent (pqac-00000017) |
| Recent 2023-2024 developments | A pharmacologic example is licochalcone A, which suppresses FBXO5 expression along with MAPK signaling and inhibits lung squamous cell carcinoma growth in vitro and in xenografts. | Primary | Fan et al., 2023, Oncology Reports | https://doi.org/10.3892/or.2023.8651 | Shows real-world experimental modulation of FBXO5 in a cancer model, though accessed pages contained limited numeric outcome values (pqac-00000027) |
| Quantitative statistics | In colorectal cancer datasets, about 12 percent of cases show EMI1 copy-number loss; these losses correlate with reduced EMI1 mRNA, higher fraction of genome altered, higher aneuploidy score, and worse disease-specific and progression-free survival. | Primary | Gudino et al., 2024, British Journal of Cancer | https://doi.org/10.1038/s41416-024-02855-9 | Reported significance includes Mann-Whitney test p less than 0.0001 for copy-loss associations (pqac-00000029) |
| Quantitative statistics | In colorectal cancer cell models, EMI1 depletion reduced EMI1 abundance to about 3 to 16 percent of control, increased aberrant chromosome spreads by 2.6 to 3.0 fold, and increased micronucleus formation by about 2.1 to 2.5 fold; endoreduplication-like spreads reached about 33 percent in HCT116 and about 60 percent in SW48. | Primary | Gudino et al., 2024, British Journal of Cancer | https://doi.org/10.1038/s41416-024-02855-9 | Provides direct functional effect sizes for chromosome-instability phenotypes after EMI1 reduction (pqac-00000029) |
| Quantitative statistics | In heterozygous EMI1 plus or minus colon-cell clones, chromosome-instability and DNA-damage readouts were significantly elevated, including gamma H2AX and 53BP1, with more than 200 nuclei analyzed per condition and p less than 0.0001 in selected comparisons. | Primary | Gudino et al., 2024, British Journal of Cancer | https://doi.org/10.1038/s41416-024-02855-9 | Strong statistical support for genome-instability and DNA-damage phenotypes (pqac-00000026) |
| Quantitative statistics | PTBP1 knockdown in A549 cells yielded 756 alternative splicing events under rMATS criteria false discovery rate at or below 0.01 and inclusion-level difference magnitude at or above 0.1; differential-expression analyses used log fold change magnitude at or above 0.5 and adjusted p below 0.05; FBXO5-S decayed faster than FBXO5-L with p below 0.001. | Primary | Li et al., 2024, Current Issues in Molecular Biology | https://doi.org/10.3390/cimb46070458 | Quantifies the scale and significance thresholds of the PTBP1 to FBXO5 splicing mechanism (pqac-00000028) |
| Quantitative statistics | Licochalcone A was tested at 0, 2, 5, 10, 20, and 40 micromolar in lung squamous cell carcinoma cells and 0 to 80 micromolar in bronchial epithelial cells across 24 to 72 hour assays; it increased G1 fraction and apoptosis and reduced xenograft tumor volume and weight. | Primary | Fan et al., 2023, Oncology Reports | https://doi.org/10.3892/or.2023.8651 | Accessed pages reported dosing and assay design but not all final IC50 or fold-change values (pqac-00000027) |
| Recent 2023-2024 developments | Open Targets lists FBXO5 disease associations including ovarian neoplasm, neurodegenerative disease, hyperaldosteronism, genital-system abnormality, and lysosomal storage disease, but evidence counts are low and should be treated as hypothesis-generating. | Database | Open Targets Platform | https://platform.opentargets.org/ | Useful for triangulation, not strong causal inference; ovarian neoplasm evidence size equals 2 in retrieved context (pqac-00000000) |


*Table: This table summarizes verified identity, mechanism, regulation, recent literature, and quantitative evidence for human FBXO5 or EMI1, UniProt Q9UKT4. It is useful as a compact evidence map linking canonical APC/C biology to recent cancer and chromosome-instability studies.*