FBXO5
Description
The FBXO5 (F-box protein 5) is a protein-coding gene located on chromosome 6.
F-box only protein 5 is a protein that in humans is encoded by the FBXO5 gene.
== Function == This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. This protein is similar to xenopus early mitotic inhibitor-1 (Emi1), which is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Moreover, Emi1 also assembles a CRL1 complex that targets RAD51 for ubiquitin-mediated degradation.
== Disease == Gene and protein expression of FBXO5/Emi1 are increased in many human cancers and increased expression has been shown to cause chromosome instability and cancer.
== Interactions == FBXO5 has been shown to interact with:
CDC20, FZR1, SKP1A. and RAD51.
FBXO5, also known as Early mitotic inhibitor 1 (Emi1), plays a crucial role in regulating the activity of the Anaphase Promoting Complex (APC) during both mitotic and meiotic cell cycles. Its function as both a substrate and an inhibitor of the APC-FZR1 complex is essential for proper cell cycle progression. During the G1 phase, FBXO5 acts as a substrate for the APC-FZR1 complex E3 ligase. However, it transitions into an inhibitor of the APC-FZR1 complex during the S and G2 phases, leading to cell cycle commitment. As an APC inhibitor, FBXO5 prevents the degradation of APC substrates by multiple mechanisms: interacting with APC to block access of APC substrates to the D-box coreceptor, suppressing ubiquitin ligation and chain elongation by preventing UBE2C and UBE2S activities. FBXO5 contributes to genome integrity by coordinating DNA replication with mitosis through APC inhibition in interphase. This stabilization of CCNA2 and GMNN promotes mitosis and prevents rereplication and DNA damage-induced cellular senescence. During oocyte maturation, FBXO5 plays a role in meiosis through inactivation of the APC-FZR1 complex. FBXO5 inhibits APC by interacting with RPS6KA2, which increases its affinity for CDC20, leading to metaphase arrest of the second meiotic division before fertilization. Furthermore, FBXO5 controls entry into the first meiotic division through inactivation of the APC-FZR1 complex. FBXO5 promotes migration and osteogenic differentiation of mesenchymal stem cells.
FBXO5 is also known as EMI1, FBX5, Fbxo31.
