| 2006 |
Evi5 stabilizes Emi1 (an APC/C inhibitor) by binding adjacent to Emi1's DSGxxS degron, blocking both degron phosphorylation by Polo-like kinases and subsequent betaTrCP binding, thereby antagonizing SCF(betaTrCP)-dependent Emi1 ubiquitination and destruction. Evi5 protein accumulates in early G1 following Plk1 destruction and is itself degraded in a Plk1- and ubiquitin-dependent manner in early mitosis. Ablation of Evi5 causes precocious Emi1 degradation, premature APC/C activation, cyclin destruction, centrosome overduplication, and mitotic catastrophe. |
Co-immunoprecipitation, in vitro ubiquitination assay, siRNA knockdown, cell-cycle imaging, kinase assays |
Cell |
High |
16439210
|
| 2007 |
Evi5 binds Rab11a and Rab11b in a GTP-dependent manner (identified by yeast two-hybrid, co-immunoprecipitation, and Biacore surface plasmon resonance), but displays no GTPase-activating activity toward Rab11 in vitro. Evi5 colocalizes with Rab11 in vivo; Rab11 effector proteins (e.g., FIP3) compete with Evi5 for Rab11 binding. Ablation of Evi5 by RNAi causes mislocalization of FIP3 at the abscission site during cytokinesis. |
Yeast two-hybrid, co-immunoprecipitation, Biacore SPR, in vitro GAP assay, RNAi knockdown, confocal microscopy |
Proceedings of the National Academy of Sciences of the United States of America |
High |
17229837
|
| 2006 |
EVI5's TBC domain functions as a GTPase-activating protein (GAP) for Rab11: EVI5 preferentially binds the GTP-bound form of Rab11 and stimulates Rab11 GTPase activity in a GAP activity assay, as demonstrated by mass spectrometry-identified complex formation and a specific Rab-binding/GAP assay. |
Linear ion trap mass spectrometry (protein complex identification), GTP-form-selective Rab-binding assay, in vitro GAP activity assay |
Oncogene |
High |
17099728
|
| 2005 |
EVI5 localizes to pericentriolar material (centrosome) in interphase cells and exists in protein complexes with both alpha- and gamma-tubulin, with both interactions mapping to the N-terminal region of EVI5. EVI5 can form dimers as shown by FPLC analysis. |
Confocal immunofluorescence microscopy, co-immunoprecipitation, GST pull-down, FPLC gel filtration |
Genomics |
Medium |
16033705
|
| 2006 |
EVI5 has a dynamic mitotic distribution: it associates with the mitotic spindle through anaphase and localizes to the midzone and midbody until completion of cytokinesis. EVI5 undergoes phosphorylation in early mitosis and proteolytic cleavage during late mitosis/cytokinesis. EVI5 co-immunoprecipitates and co-purifies (GST pull-down) with the chromosomal passenger complex (INCENP, Aurora B kinase, survivin). siRNA knockdown of EVI5 produces a multinucleate phenotype, establishing an essential role in cytokinesis completion. |
Immunofluorescence microscopy, co-immunoprecipitation, GST pull-down, siRNA knockdown, Western blot for phosphorylation/cleavage |
Experimental cell research |
Medium |
16764853
|
| 2012 |
Drosophila Evi5 promotes collective border cell migration through its Rab-GAP activity directed at Rab11. Both loss and gain of Evi5 function block border cell migration by disrupting Rab11-dependent polarization of active guidance receptors. The TBC/Rab-GAP domain is required for this function. |
Drosophila genetic screen for Rab-GAP proteins, loss-of-function and gain-of-function genetics, in vivo imaging of border cell migration, Rab11 activity reporters |
The Journal of cell biology |
High |
22778279
|
| 1998 |
The human EVI5 gene (NB4S) encodes an 810 amino acid protein with a TBC1 box motif (homologous to genes involved in cell growth/differentiation) and C-terminal coiled-coil domains. It is disrupted by a constitutional t(1;10)(p22;q21) translocation in a neuroblastoma patient, generating a fusion transcript that combines the TBC1 motif of NB4S with a polyadenylation signal from TRNG10, potentially producing a truncated oncogenic protein. |
Molecular cloning of translocation breakpoints, sequence analysis, Northern blot expression analysis |
Human molecular genetics |
Medium |
9618176
|
| 2009 |
EVI5 overexpression prevents Runx1-deficient hematopoietic stem cell (HSC) exhaustion in mice, identified by retroviral insertional mutagenesis as a cooperating genetic alteration in leukemia development. EVI5 activation maintains pre-leukemic stem cell populations in the context of Runx1 loss. |
Retroviral insertional mutagenesis screen, conditional Runx1 knockout mouse model, retroviral EVI5 overexpression rescue experiment |
Blood |
Medium |
20008790
|
| 2020 |
Evi5 interacts with c-Myc and antagonizes FBXW7 E3 ligase-mediated ubiquitination and degradation of c-Myc protein, thereby stabilizing c-Myc and promoting its transcriptional activity in laryngeal squamous cell carcinoma cells. CRISPR-mediated Evi5 knockout decreases c-Myc levels, causes G1 arrest, and reduces tumor growth in vivo. |
Co-immunoprecipitation, CRISPR knockout, luciferase transcriptional reporter assay, flow cytometry, xenograft mouse model |
Cancer cell international |
Medium |
32047362
|
| 2020 |
EVI5 interacts with TGF-β receptor I and TGF-β receptor II (shown by co-immunoprecipitation), and the miR-486-5p–EVI5 axis affects NSCLC migration and invasion through the TGF-β/Smad signaling pathway. EVI5 also interacts with Emi1 in NSCLC cells. |
Co-immunoprecipitation, siRNA knockdown, wound healing/transwell invasion assays, xenograft mouse model |
Journal of experimental & clinical cancer research : CR |
Low |
32393392
|
| 2015 |
An exonic SNP in EVI5 associated with multiple sclerosis risk induces changes in superficial hydrophobicity patterns of the EVI5 coiled-coil domain, altering the EVI5 interactome. Immunoprecipitation followed by mass spectrometry of wild-type vs. risk-variant EVI5 revealed disease-specific interactors linked to lipid metabolism, including a novel interaction with sphingosine 1-phosphate lyase (SGPL1) exclusive to the risk variant. |
Fine mapping/meta-analysis, co-immunoprecipitation followed by mass spectrometry, structural modeling of coiled-coil domain |
Human molecular genetics |
Medium |
26433934
|
| 2024 |
Drosophila Evi5 is required for intracellular iron trafficking: Evi5 depletion in the prothoracic gland disrupts vesicle morphology, blocks endosome recycling, and impairs transferrin-1 trafficking, reducing cellular iron and impairing heme synthesis. Evi5 physically interacts with ferritin, and ferritin injection rescues developmental delays caused by Evi5 depletion. |
RNAi depletion in Drosophila prothoracic gland, electron microscopy of vesicle morphology, ferritin co-immunoprecipitation/physical interaction assay, ferritin injection rescue experiment |
Nature communications |
Medium |
38744835
|
| 2025 |
EVI5 interacts with Rab11 and upregulates PD-L1 expression in lung adenocarcinoma cells. EVI5 knockout suppresses Rab11 and PD-L1 expression, while EVI5 overexpression promotes their expression, defining an EVI5–Rab11–PD-L1 regulatory axis. |
Co-immunoprecipitation, CRISPR knockout, overexpression, Western blot |
Scientific reports |
Low |
41258404
|
| 2025 |
EVI5 promotes lung adenocarcinoma progression through activation of the ERK1/2–c-Myc signaling axis; EVI5 knockout reduces ERK1/2 and c-Myc activity, and an ERK1/2 pathway inhibitor phenocopies EVI5 loss, validated by functional rescue experiments. |
CRISPR knockout, overexpression, Western blot, ERK1/2 inhibitor functional rescue, immunofluorescence, qRT-PCR |
Current cancer drug targets |
Low |
40525449
|
| 2022 |
Evi5 is required for Xenopus limb and tail regeneration: morpholino-mediated Evi5 knockdown reduces blastema cell proliferation, causes apoptosis, and blocks blastema formation. RNA-seq reveals Evi5 knockdown downregulates PDGFα and TGFβ signaling pathways as well as lysine demethylases Kdm6b and Kdm7a, which are themselves required for limb regeneration. |
Morpholino antisense knockdown in Xenopus tadpoles, RNA-sequencing, proliferation and apoptosis assays, Kdm6b/Kdm7a knockdown epistasis |
Frontiers in cell and developmental biology |
Medium |
36605717
|