Alternative titles; symbols
HGNC Approved Gene Symbol: EVI5
Cytogenetic location: 1p22.1 Genomic coordinates (GRCh38): 1:92,508,696-92,792,410 (from NCBI)
Roberts et al. (1998) cloned the breakpoints of a constitutional t(1;10)(p22;q21) translocation in a child with stage 4S neuroblastoma (256700). They identified the gene on chromosome 1 as EVI5, which they called NB4S, and obtained a full-length NB4S cDNA by database analysis, screening a liver cDNA library, and 5-prime RACE of adult brain total RNA. The deduced 810-amino acid protein shares 88% identity with mouse Evi5. A 200-amino acid region of NB4S shares significant homology with TBC1 box motif proteins (see 609850) involved in cell growth and differentiation. The C-terminal end of the protein contains a number of coiled-coil domains, indicating a possible protein-protein binding function. Northern blot analysis detected a 7.5-kb transcript in a wide variety of tissues.
The anaphase-promoting complex/cyclosome (APC/C) inhibitor EMI1 (FBXO5; 606013) controls progression to S phase and mitosis by stabilizing key APC/C ubiquitination substrates, including cyclin A (CCNA2; 123835). Eldridge et al. (2006) found that endogenous EVI5 and EMI1 coprecipitated from human embryonic kidney cell lysates and that the recombinant proteins interacted in vitro. Each protein bound the other through its N terminus. Immunofluorescence microscopy localized EVI5 predominantly to centrosomes in interphase human osteosarcoma cells, and centrosomal localization required the C-terminal half of EVI5. In synchronized HeLa cells, EVI5 accumulated in early G1 phase, reached maximal level by late G1, and decreased in early mitosis concomitantly with EMI1 in a ubiquitin- and proteasome-dependent manner. Degradation of EVI5 in early mitosis required phosphorylation of EVI5 by PLK1 (602098). In vivo and in vitro experiments showed that EVI5 stabilized EMI1 during interphase by binding to a site adjacent to the EMI1 degron and blocking both PLK-dependent degron phosphorylation and subsequent BTRC (603482) binding. By doing so, EVI5 antagonized ubiquitin-dependent destruction of EMI1 by the BTRC-containing SCF complex. Ablation of EVI5 by small interfering RNA caused precocious degradation of EMI1, premature APC/C activation, cyclin destruction, cell cycle arrest, centrosome overduplication, and mitotic catastrophe. Eldridge et al. (2006) concluded that EVI5 serves as a critical regulator of cell cycle progression by defining a window of stability for EMI1 during interphase analogous to the window of stability provided by EMI1 for APC/C substrates over a similar period.
By genomic sequence analysis, Roberts et al. (1998) mapped the EVI5 gene to chromosome 1p22.
Roberts et al. (1998) cloned the breakpoints of a constitutional t(1;10)(p22;q21) translocation in a child with stage 4S neuroblastoma. The chromosome 1 breakpoint interrupted NB4S, and the chromosome 10 breakpoint interrupted a novel transcript, called TRNG10, that could only be detected in tumor cells. This transcript has no exon/intron structure or significant open reading frame, suggesting that it is a structural RNA that is transcribed but not translated. The chromosome rearrangement created a fusion gene product that combined the TBC1 motif of NB4S with a polyadenylation signal from TRNG10, potentially generating a truncated protein with oncogenic properties.
Eldridge, A. G., Loktev, A. V., Hansen, D. V., Verschuren, E. W., Reimann, J. D. R., Jackson, P. K. The Evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor Emi1. Cell 124: 367-380, 2006. Note: Erratum: Cell 124: 1301-1302, 2006. [PubMed: 16439210] [Full Text: https://doi.org/10.1016/j.cell.2005.10.038]
Roberts, T., Chernova, O., Cowell, J. K. NB4S, a member of the TBC1 domain family of genes, is truncated as a result of a constitutional t(1;10)(p22;q21) chromosome translocation in a patient with stage 4S neuroblastoma. Hum. Molec. Genet. 7: 1169-1178, 1998. [PubMed: 9618176] [Full Text: https://doi.org/10.1093/hmg/7.7.1169]