FBXO5

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. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Dec 2008]

F-Box Protein 5

Regulator of APC activity during mitotic and meiotic cell cycle (PubMed:17485488, PubMed:17234884, PubMed:17875940, PubMed:23708001, PubMed:23708605, PubMed:16921029).

During mitotic cell cycle plays a role as both substrate and inhibitor of APC-FZR1 complex (PubMed:29875408, PubMed:17485488, PubMed:17234884, PubMed:17875940, PubMed:23708001, PubMed:23708605, PubMed:16921029).

During G1 phase, plays a role as substrate of APC-FZR1 complex E3 ligase (PubMed:29875408).

Then switches as an inhibitor of APC-FZR1 complex during S and G2 leading to cell-cycle commitment (PubMed:29875408).

As APC inhibitor, prevents the degradation of APC substrates at multiple levels: by interacting with APC and blocking access of APC substrates to the D-box coreceptor, formed by FZR1 and ANAPC10; by suppressing ubiquitin ligation and chain elongation by APC by preventing the UBE2C and UBE2S activities (PubMed:23708605, PubMed:23708001, PubMed:16921029).

Plays a role in genome integrity preservation by coordinating DNA replication with mitosis through APC inhibition in interphase to stabilize CCNA2 and GMNN in order to promote mitosis and prevent rereplication and DNA damage-induced cellular senescence (PubMed:17234884, PubMed:17485488, PubMed:17875940).

During oocyte maturation, plays a role in meiosis through inactivation of APC-FZR1 complex. Inhibits APC through RPS6KA2 interaction that increases FBXO5 affiniy for CDC20 leading to the metaphase arrest of the second meiotic division before fertilization (By similarity).

Controls entry into the first meiotic division through inactivation of APC-FZR1 complex (By similarity).

Promotes migration and osteogenic differentiation of mesenchymal stem cells (PubMed:29850565).

Cell division Source: UniProtKB-KW
Microtubule polymerization Source: Ensembl
Negative regulation of cellular senescence Source: UniProtKB
Negative regulation of DNA endoreduplication Source: UniProtKB
Negative regulation of meiotic nuclear division Source: GO_Central
Negative regulation of mitotic metaphase/anaphase transition Source: UniProtKB
Negative regulation of response to DNA damage stimulus Source: UniProtKB
Negative regulation of ubiquitin protein ligase activity Source: UniProtKB
Negative regulation of ubiquitin-protein transferase activity Source: UniProtKB
Oocyte maturation Source: Ensembl
Positive regulation of biomineral tissue development Source: UniProtKB
Positive regulation of cell population proliferation Source: UniProtKB
Positive regulation of G2/M transition of mitotic cell cycle Source: UniProtKB
Positive regulation of mesenchymal stem cell migration Source: UniProtKB
Positive regulation of osteoblast differentiation Source: UniProtKB
Protein ubiquitination Source: UniProtKB-UniPathway
Regulation of DNA replication Source: UniProtKB
Regulation of mitotic cell cycle Source: UniProtKB
Regulation of mitotic nuclear division Source: GO_Central
Spindle assembly involved in female meiosis I Source: Ensembl
Vesicle organization Source: Ensembl

Nucleus; Spindle; Cytoplasm. In interphase, localizes in a punctate manner in the nucleus and cytoplasm with some perinuclear concentration (PubMed:11988738). In mitotic cells, localizes throughout the cell, particularly at the spindle (PubMed:15469984).

Phosphorylation by CDK2 and subsequently by PLK1 triggers degradation during early mitosis through ubiquitin-mediated proteolysis by the SCF ubiquitin ligase complex containing the F-box protein BTRC. This degradation is necessary for the activation of APC in late mitosis and subsequent mitotic progression (PubMed:12791267, PubMed:15469984). Phosphorylated by RPS6KA2; increases and stabilizes interaction with CDC20 (By similarity).
Ubiquitinated by the SCF(BTRC) complex following phosphorylation by PLK1 (PubMed:15469984). Undergoes both 'Lys-11' and 'Lys-48'-linked polyubiquitination by APC-FZR1 complex leading to degradation by proteasome during G1 phase (PubMed:29875408). Degraded through the SCF(BTRC) complex; degradation occurs during oocyte maturation, between germinal vesicle breakdown (GVBD) and meiosis I, and is required for the meiosis I-meiosis II transition (By similarity).