Alternative titles; symbols
HGNC Approved Gene Symbol: FBXO6
Cytogenetic location: 1p36.22 Genomic coordinates (GRCh38): 1:11,664,200-11,674,354 (from NCBI)
The F box, named after cyclin F (CCNF; 600227), in which it was originally observed, is an approximately 40-amino acid motif that binds SKP1 (601434). F-box proteins, such as FBXO6, are components of modular E3 ubiquitin protein ligases called SCFs (SKP1, cullin (see 603134), F-box proteins), which function in phosphorylation-dependent ubiquitination.
Using a yeast 2-hybrid screen with SKP1 as bait, followed by searching sequence databases, Winston et al. (1999) and Cenciarelli et al. (1999) identified 33 mammalian and 26 human F-box proteins, respectively. These contained C termini with leucine-rich repeats (FBXLs, e.g., SKP2 (601436)), WD40 domains (FBXWs, e.g., BTRCP (603482)), or no recognizable motifs (FBXOs, e.g., CCNF).
By searching sequence databases, Ilyin et al. (2000) identified a cDNA encoding FBXO6, which they termed FBG2. The deduced 293-amino acid protein has an N-terminal F box and a C terminus that is highly homologous to the rat 42-kD neural F-box protein (Nbf42), with which it shares several conserved glycine residues (termed the G domain). RNA blot analysis revealed wide expression of FBXO6, with highest levels in brain, skeletal muscle, spleen, liver, and testis.
Du et al. (2019) found that FBXO6 negatively regulated the activation of type I interferon (IFN-I) signaling triggered by dsDNA, RNA, or viral infection by inhibiting IRF3 (603734) dimerization. FBXO6 bound to IRF3 downstream of the IFN-I signaling pathway, via the interaction between its FBA domain and IAD domain of IRF3, thereby regulating IRF3 degradation through a ubiquitination-mediated proteasome degradation pathway in an SCF complex-independent manner.
Ilyin et al. (2002) determined that the FBXO6 gene contains 6 exons and spans about 10.2 kb. Exon 1 is noncoding.
By genomic sequence analysis, Ilyin et al. (2002) mapped the FBXO6 gene to chromosome 1p36, between the FBXO44 gene (609111) and the MAD2L2 gene (604094). Jin et al. (2004) stated that the FBXO6 gene maps to chromosome 1p36.23 and the mouse Fbxo6 gene maps to chromosome 4E2.0.
Cenciarelli, C., Chiaur, D. S., Guardavaccaro, D., Parks, W., Vidal, M., Pagano, M. Identification of a family of human F-box proteins. Curr. Biol. 9: 1177-1179, 1999. [PubMed: 10531035] [Full Text: https://doi.org/10.1016/S0960-9822(00)80020-2]
Du, X., Meng, M., Peng, D., Wang, Z., Ouyang, W., Han, Y., Gu, Y., Fan, L., Wu, F., Jiang, X., Xu, F., Qin, F. X.-F. Noncanonical role of FBXO6 in regulating antiviral immunity. J. Immun. 203: 1012-1020, 2019. [PubMed: 31308089] [Full Text: https://doi.org/10.4049/jimmunol.1801557]
Ilyin, G. P., Rialland, M., Pigeon, C., Guguen-Guillouzo, C. cDNA cloning and expression analysis of new members of the mammalian F-box protein family. Genomics 67: 40-47, 2000. [PubMed: 10945468] [Full Text: https://doi.org/10.1006/geno.2000.6211]
Ilyin, G. P., Serandour, A.-L., Pigeon, C., Rialland, M., Glaise, D., Guguen-Guillouzo, C. A new subfamily of structurally related human F-box proteins. Gene 296: 11-20, 2002. [PubMed: 12383498] [Full Text: https://doi.org/10.1016/s0378-1119(02)00867-3]
Jin, J., Cardozo, T., Lovering, R. C., Elledge, S. J., Pagano, M., Harper, J. W. Systematic analysis and nomenclature of mammalian F-box proteins. Genes Dev. 18: 2573-2580, 2004. [PubMed: 15520277] [Full Text: https://doi.org/10.1101/gad.1255304]
Winston, J. T., Koepp, D. M., Zhu, C., Elledge, S. J., Harper, J. W. A family of mammalian F-box proteins. Curr. Biol. 9: 1180-1182, 1999. [PubMed: 10531037] [Full Text: https://doi.org/10.1016/S0960-9822(00)80021-4]