FBXL5 explained

F-box/LRR-repeat protein 5 is a protein that in humans is encoded by the FBXL5 gene.^{[1] [2]}

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. Alternative splicing of this gene generates 2 transcript variants.

FBXL5 is an iron and oxygen sensor. It promotes IRP2 ubiquitination and then its degradation in an iron- and oxygen-dependent manner. The cryo-EM structure of the FBXL5-IRP2 complex revealed an unexpected 2Fe2S cluster embedded in the leucine-rich repeats domain of the F-box protein in close vicinity of the protein-protein interaction interface.^[3] FBXL5, therefore, is an iron-sulfur protein. FBXL5 can only engage IRP2 when its 2Fe2S cluster is in the oxidized state, which explains how oxygen tension dictates IRP2 stability.

Further reading

• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA . A "double adaptor" method for improved shotgun library construction . Analytical Biochemistry . 236 . 1 . 107–113 . April 1996 . 8619474 . 10.1006/abio.1996.0138 .
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA . Large-scale concatenation cDNA sequencing . Genome Research . 7 . 4 . 353–358 . April 1997 . 9110174 . 139146 . 10.1101/gr.7.4.353 .
• Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW . A family of mammalian F-box proteins . Current Biology . 9 . 20 . 1180–1182 . October 1999 . 10531037 . 10.1016/S0960-9822(00)80021-4 . 14341845 . free . 1999CBio....9.1180W .
• Ilyin GP, Rialland M, Pigeon C, Guguen-Guillouzo C . cDNA cloning and expression analysis of new members of the mammalian F-box protein family . Genomics . 67 . 1 . 40–47 . July 2000 . 10945468 . 10.1006/geno.2000.6211 .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–1795 . November 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Research . 11 . 3 . 422–435 . March 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A . From ORFeome to biology: a functional genomics pipeline . Genome Research . 14 . 10B . 2136–2144 . October 2004 . 15489336 . 528930 . 10.1101/gr.2576704 .
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S . The LIFEdb database in 2006 . Nucleic Acids Research . 34 . Database issue . D415-D418 . January 2006 . 16381901 . 1347501 . 10.1093/nar/gkj139 .
• Zhang N, Liu J, Ding X, Aikhionbare F, Jin C, Yao X . FBXL5 interacts with p150Glued and regulates its ubiquitination . Biochemical and Biophysical Research Communications . 359 . 1 . 34–39 . July 2007 . 17532294 . 10.1016/j.bbrc.2007.05.068 .

Notes and References

1. Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M . Identification of a family of human F-box proteins . Current Biology . 9 . 20 . 1177–1179 . October 1999 . 10531035 . 10.1016/S0960-9822(00)80020-2 . 7467493 . free . 1999CBio....9.1177C .
2. Web site: Entrez Gene: FBXL5 F-box and leucine-rich repeat protein 5.
3. Wang H, Shi H, Rajan M, Canarie ER, Hong S, Simoneschi D, Pagano M, Bush MF, Stoll S, Leibold EA, Zheng N . FBXL5 Regulates IRP2 Stability in Iron Homeostasis via an Oxygen-Responsive [2Fe2S] Cluster . Molecular Cell . 78 . 1 . 31–41.e5 . April 2020 . 32126207 . 7159994 . 10.1016/j.molcel.2020.02.011 .