The gene is encoded by 23 exons that are located on chrosome 2p16.3 (NM_025133.4). The first ATG occurs in exon 2. There is an alternatively spliced transcript variant encoding an isoform in which the first ATG occurs in exon 1 (NM_001190274).

3.8 kb mRNA; 2532 bp open reading frame (for NM_025133.4). 4 kb mRNA; 2784 bp open reading frame (for NM_001190274).

The fbxo11 gene encodes the FBXO11 protein which has 843 amino acids (NP_079409.3), with an estimated molecular weight of 94 kDa. The protein contains from N-term to C-term, an F-box domain, three CASH domains (domain present in carbohydrate binding proteins and sugar hydrolyses), and a Zinc finger domain. Other splice variants were reported (Cook et al., 2006).

Widely expressed.

Mainly nuclear.

Substrate recognition component of the SCF^FBXO11 ubiquitin ligase complex consisting of CUL1, RBX1, SKP1 and FBXO11. Known interactors include p53, BCL6, CDT2, Blimp and Snail (Figure 2).
FBXO11 functions in lymphomagenesis
The SCF^FBXO11 complex mediates ubiquitylation and degradation of BCL6, a transcription repressor that is required for normal germinal center development. Constitutive expression of BCL6 occurs in at least 70% patients with diffuse large B-cell lymphoma (DLBCL). The gene encoding FBXO11 was found to be deleted or mutated in multiple DLBCL cell lines, and this inactivation of FBXO11 correlated with increased levels and stability of BCL6 (Duan et al., 2012). Moreover, FBXO11 is deleted or mutated in 12-15% of primary DLBCL.
Fbxo11 in cell cycle regulation
FBXO11 interacts with CDT2 (a DCAF protein that controls cell-cycle progression) and recruits CDT2 to the SCF^FBXO11 complex to promote its proteasomal degradation (Abbas et al., 2013; Rossi et al., 2013). CDK-mediated phosphorylation of Thr464 present in the CDT2 degron inhibits recognition by FBXO11 (Rossi et al., 2013). Inhibition of SCF^FBXO11-mediated CDT2 degradation result in a delay in cell-cycle exit in response to serum deprivation or TGFβ treatment. The functional interaction between FBXO11 and CDT2 is evolutionary conserved from worms to humans and plays an important role in regulating the timing of cell-cycle exit.
FBXO11 in TGFβ signaling pathway
FBXO11 was implicated in the TGFβ signaling pathway. Mice with inactivated FBXO11 exhibited significant phospho-Smad2 (P-Smad2) nuclear staining in the epithelial cells of palatal shelves, eyelids, and airways of the lung, potentially leading to the developmental defects of these tissues (Tateossian et al., 2009).
SCF^FBXO11-mediated degradation of CDT2 was shown to contribute to the stabilization of the CRL4^CDT2 substrate p21 and Set8 in response to serum withdraw and TGFβ stimulation (Abbas et al., 2013; Rossi et al., 2013). Depletion of FBXO11 was shown also to inhibit lung adenocarcinoma eptithelial cells migration (Abbas et al., 2013).
FBXO11 in the regulation of cell metastasis
FBXO11 was shown to mediate the ubiquitylation and degradation of SNAIL (Zheng et al., 2014), a transcription factor that promotes epithelial-mesenchymal transition (EMT). The recognition of SNAIL by FBXO11 appears to be dependent on Ser-11 phosphorylation of SNAIL by protein kinase D1 (PDK1). FBXO11 blocks SNAIL-induced EMT, tumor initiation, and metastasis in multiple breast cancer models.
DRE-1/FBXO11 in C. elegans development
The C. elegans ortholog of FBXO11 is DRE-1, whose mutant phenotypes include precocious terminal differentiation of epidermal stem cells and altered temporal patterning of gonadal outgrowth (Fielenbach et al., 2007). DRE-1 forms a functional SCF ubiquitin ligase, and was reported to target the conserved transcription factor BLMP-1 for proteasomal degradation (Horn et al., 2014). The DRE-1 - BLMP-1 axis was important for regulating developmental timing within the heterochronic circuit during late larval development. blmp-1 deletion was shown to suppress dre-1 mutant phenotypes and exhibit developmental timing defects opposite to dre-1.
Other functions
FBXO11 has been shown to act as an adaptor protein to mediate the neddylation of p53, which leads to the suppression of p53 transcriptional activity. SCF^FBXO11 does not mediate the ubiquitylation of p53 (Abida et al., 2007).

Human FBXO11 is highly conserved in evolution that shares 100% amino acid identity with Pan troglodytes, 99.8% identity with Canis lupus familiaris, 99.5% identity with Mus musculus, and 61% identity with C. elegans.

FBXO11-inactivating mutations contribute to the pathogenesis of diffuse large B cell lymphoma (DLBCL) through stabilization of BCL6 (Duan et al., 2012). FBXO11 mutations were also identified in other human cancers, such as colon, lung, ovary, and head and neck tumors (Kan et al., 2010; Lohr et al., 2012; Stransky et al., 2011; Yoshida et al., 2011). In mice, a homozygous mutation of Fbxo11 results in cleft palate defects, facial clefting, and perinatal lethality. Moreover, haploinsufficient mutant alleles cause otitis media, a disorder that affects approximately 15% of children (Hardisty-Hughes et al., 2006).