FBXL3

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 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 Fbls class and, in addition to an F-box, contains several tandem leucine-rich repeats and is localized in the nucleus. [provided by RefSeq]

Full Name

F-box and leucine-rich repeat protein 3

Research Area

Substrate-recognition component of the SCF(FBXL3) E3 ubiquitin ligase complex involved in circadian rhythm function. Plays a key role in the maintenance of both the speed and the robustness of the circadian clock oscillation (PubMed:17463251, PubMed:23452855, PubMed:27565346).

The SCF(FBXL3) complex mainly acts in the nucleus and mediates ubiquitination and subsequent degradation of CRY1 and CRY2 (PubMed:17463251, PubMed:23452855, PubMed:27565346).

Activity of the SCF(FBXL3) complex is counteracted by the SCF(FBXL21) complex (PubMed:23452855).

Biological Process

Entrainment of circadian clock by photoperiod Source: UniProtKB
G2/M transition of mitotic cell cycle Source: GO_Central
Protein destabilization Source: UniProtKB
Protein ubiquitination Source: UniProtKB
Regulation of cell cycle Source: GO_Central
Regulation of circadian rhythm Source: UniProtKB
Rhythmic process Source: UniProtKB-KW
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB

Cellular Location

Nucleus; Cytoplasm. Predominantly nuclear.

Involvement in disease

Intellectual developmental disorder with short stature, facial anomalies, and speech defects (IDDSFAS):
An autosomal recessive disorder characterized by global developmental delay, mildly to severely impaired intellectual development, delayed or slurred speech, and short stature. Dysmorphic features included a large bulbous nose and variable microretrognathia. Some patients show joint hyperlaxity and dislocations.

PTM

Undergoes autophagy-mediated degradation in the liver in a time-dependent manner.