F-Box/Wd Repeat-Containing Protein 4 (FBXW4) Human Recombinant Protein

This gene is a member of the F-box/WD-40 gene family, which recruit specific target proteins through their WD-40 protein-protein binding domains for ubiquitin mediated degradation. In mouse, a highly similar protein is thought to be responsible for maintaining the apical ectodermal ridge of developing limb buds; disruption of the mouse gene results in the absence of central digits, underdeveloped or absent metacarpal/metatarsal bones and syndactyly. This phenotype is remarkably similar to split hand-split foot malformation in humans, a clinically heterogeneous condition with a variety of modes of transmission. An autosomal recessive form has been mapped to the chromosomal region where this gene is located, and complex rearrangements involving duplications of this gene and others have been associated with the condition. A pseudogene of this locus has been mapped to one of the introns of the BCR gene on chromosome 22. [provided by RefSeq, Jul 2008]

FBXW4: Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. Likely to be involved in key signaling pathways crucial for normal limb development. May participate in Wnt signaling. Defects in FBXW4 are a cause of split-hand/foot malformation type 3 (SHFM3). SHFM3 is an autosomal dominant disorder characterized by hypoplasia/aplasia of the central digits with fusion of the remaining digits.

Protein type: Cell development/differentiation; Cell cycle regulation

Chromosomal Location of Human Ortholog: 10q24

Cellular Component: ubiquitin ligase complex

Biological Process: cartilage development; embryonic digit morphogenesis; embryonic limb morphogenesis; positive regulation of mesenchymal cell proliferation; ubiquitin-dependent protein catabolic process; Wnt receptor signaling pathway

Disease: Split-hand/foot Malformation 3