FBXO31 encodes one mRNA transcript, published analyses have not reordered alternative five prime transcript or start sequences.

FBXO31 is 3,635-bp in length, composed of 9 exons (1 to 9) spanning approximately 55-kb of genomic DNA, and has an ORF of 1,620-bp encoding a protein of 539 amino acids with a predicted mass of 61-kDa.

Alternative five prime transcripts may exist. Homologous mouse cDNA sequences extending further five prime have been used for RT-PCR to identify putative translation start sites and established that alternatively spliced five prime exons result in short and long isoforms. The short isoform is 3,635-bp in length (i.e. approximately with poly A), and is the predicted primary transcript. The long isoform is 3,725-bp in length, contains an additional five prime exon of 87-bp and has an ORF of 1,707-bp encoding a protein of 568 amino acids. An additional smaller isoform of 3,099-bp with an ORF of 1,104-bp and 367 amino acids was predicted in GenBank.

FBXO31 contains a moderate density C + G rich region (66% G + G with 9% CpG) spanning approximately 2.48-kb located within and five prime to the 350-bp exon 1.

The FBXO31 transcript has and an uncharacteristically short 23-bp five prime untranslated region.

None identified.

FBXO31 contains no significant homology to other known proteins apart from a characteristic 40 amino acid F-box domain at the COOH-terminal end.

FBXO31 forms part of the FBXO class of F-box proteins. Comparison of FBXO31 with the F-box domain of functionally demonstrated F-box proteins (i.e. Fbx1, Fbx2, Fbw1a, Fbw1b and Fbl1 ) indicates that FBXO31 matches the F-box consensus more closely than recognized F-box proteins from each of the three classes. Most F-box proteins notated as FBXO do not have recognizable substrate binding domains. In one instance Fbx7 has been shown to contain a proline-rich region that functions with SCF complexes in regulating Cdk1 - cyclin B - phosphorylated hepatoma up-regulated protein ( HURP ) proteolysis. This proline-rich region has been found in other FBXO proteins. The COOH-terminal end of FBXO31 contains a 175-aa glycine and arginine rich region with possible similar function.

FBXO31 contains six minimal D-box (RxxL) motifs. Proteins with RxxL motifs are often degraded via the APC/C( Cdh1 ) ubiquitin ligase.

FBXO31 is widely expressed as a 3.6-kb transcript at similar levels in breast, testis, ovary, liver, uterus, prostate, colon, stomach, bladder, spinal cord, pancreas, trachea, kidney and thyroid. High expression is found in brain and low expression in bone marrow. FBXO31 is represented by the unigene cluster Hs.567582. cDNA clones from Hs.567582 express in the adrenal gland, blood, colon, germ cells, heart, kidney, liver, lung, muscle, placenta, synovial membrane, tonsil, cervix, lymph tissue, skin, mammary gland, testis, ovary, uterus, prostate, stomach, bladder, spinal cord, pancreas, thyroid and brain.

Co-immunoprecipitation experiments indicate that the carboxy terminal domain of FBXO31 associates with the Skp1, Roc-1 and Cullin-1 proteins. Immuno-localization studies demonstrate that ectopic expression of FBXO31 causes a change of Skp1 localization from the nucleus to the cytoplasm. The Skp1 protein returns to a nuclear localization when co-expressed with a FBXO31 protein with a deleted F-box domain.

FBXO31 is associated with the Skp1, Roc-1 and Cullin-1 proteins through its substrate F-box recognition domain and forms part of an SCF ubiquitination complex.
The ubiquitin-dependant proteasome degradation pathway regulates protein abundance and the function of oncogenes, tumor suppressors, transcription factors and other signaling molecules. Ubiquitination begins with the addition of ubiquitin moieties to target proteins and follows a multi-step process, the end point being proteolysis of polyubiquitinated substrates by a 26S multi-protein complex. Ubiquitination of substrates targeted for degradation requires 3 classes of enzymes; the ubiquitin-activating enzymes (E1), the ubiquitin conjugating enzymes (E2) and the ubiquitin ligases (E3). E3 proteins participate in cell cycle progression. SCF complexes (a class of E3 ligases) regulate the G1-S phase transition. A wide variety of SCF targets include G1 phase cyclins, cyclin-dependant kinase inhibitors, DNA replication factors and transcription factors that promote cell cycle progression.
F-box containing proteins act as substrate recognition components of the SCF ubiquitin-ligase complexes in the ubiquitin-dependant proteasome degradation pathway. These complexes contain four components; Skp1, Cullin, Rbx-Rocl-Hrtl and an F-box protein. The F-box motif tethers the F-box protein to other components of the SCF complex by binding the core SCF component Skp1. This motif is generally found in the amino half of the proteins and is often coupled with other protein domains in the variable carboxy terminus of the protein. The most common carboxy terminal domains include leucine-rich repeats (LRRs) and WD-40 domains. Regions rich in glycine and arginine have also been implicated as protein binding domains, although such domains contain a more definitive repeat region than present in FBXO31.
F-box SCF ubiquitin ligase complexes are involved in proteolysis pathways critical to diverse cellular functions including muscle atrophy, DNA metabolism, ER-associated degradation, desmin-related myopathy, signal transduction, control of G1-S progression and orderly execution of cell cycle. Skp1, Cul1 and Rbx1 are invariant proteins of the SCF complex while the F-box proteins that bind to Skp1 are the components that impart functional specificity. For instance Skp2 specifically binds phosphorylated p27 resulting in its degradation and control of S phase entry in the cell cycle.

F-box domain containing no other significant homology.

None recorded.