FBXO25 is 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. FBXO25 belongs to the Fbxs class. There are three named isoforms produced by alternative splicing. FBXO25, also known as FBX25, is a 367 amino acid protein that contains one C-terminal F-box domain and belongs to the Fbx class of the F-box family of proteins. F-box proteins are critical components of the SCF (Skp1-CUL-1-F-box protein) type E3 ubiquitin ligase complex and are involved in substrate recognition and recruitment for ubiquitination. They are members of a larger family of proteins that are involved in the regulation of a wide variety of cellular processes (including the cell cycle, immune response, signaling cascades and developmental processes) through the targeting of proteins, such as cyclins, cyclin-dependent kinase inhibitors, IkB-a and b-catenin, for degradation by the proteasome after ubiquitination. Expressed at high levels in brain, FBXO25 localizes predominantly to the nucleus and directly interacts with Skp1 p19 and CUL-1. Disruption of the gene encoding FBXO25 can lead to X-linked mental retardation.
Function: Substrate-recognition component of the SCF(SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Mayplay a role in accumulation of expanded polyglutamine (polyQ)protein huntingtin (HTT) (By similarity).
Subunit: Part of a SCF (SKP1-cullin-F-box) protein ligase complexconsisting of FBXO25, SKP1, CUL1 and RBX1. Interacts directly withSKP1 and CUL1. Interacts (via C-terminus) with beta-actin (viaN-terminus).
Subcellular Location: Nuclear. Note=In the nucleus, associateswith a subnuclear dot-like structure. Colocalized with SKP1
Tissue Specificity: Expressed in all brain tissue observed.
DISEASE: Note=A chromosomal aberration involving FBXO25 is a causeof X-linked mental retardation (XLMR). Translocationt(X;8)(p11.22;p23.3) with SHROOM4.