FBXL5

FBXL5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3U9J, 3U9M, 3V5X, 3V5Y, 3V5Z
Identifiers
Aliases	FBXL5 , FBL4, FBL5, FLR1, F-box and leucine-rich repeat protein 5, F-box and leucine rich repeat protein 5
External IDs	OMIM: 605655; MGI: 2152883; HomoloGene: 8129; GeneCards: FBXL5; OMA:FBXL5 - orthologs
Gene location (Human) Chr. Chromosome 4 (human) [1] Band 4p15.32 Start 15,604,381 bp [1] End 15,681,679 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5|5 B3 Start 43,901,957 bp [2] End 43,978,980 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte Epithelium of choroid plexus Achilles tendon kidney tubule blood seminal vesicula germinal epithelium oocyte secondary oocyte sperm Top expressed in spermatocyte granulocyte otolith organ utricle spermatid neural layer of retina lobe of cerebellum gastrula cerebellar vermis habenula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function iron ion binding protein binding metal ion binding ubiquitin-protein transferase activity Cellular component ubiquitin ligase complex cytoplasm SCF ubiquitin ligase complex perinuclear region of cytoplasm cytosol Biological process SCF-dependent proteasomal ubiquitin-dependent protein catabolic process protein ubiquitination iron ion homeostasis protein polyubiquitination cellular iron ion homeostasis post-translational protein modification ubiquitin-dependent protein catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 26234 242960 Ensembl ENSG00000118564 ENSMUSG00000039753 UniProt Q9UKA1 Q8C2S5 RefSeq (mRNA) NM_001193534 NM_001193535 NM_012161 NM_001159963 NM_178729 RefSeq (protein) NP_001180463 NP_001180464 NP_036293 NP_001153435 NP_848844 Location (UCSC) Chr 4: 15.6 – 15.68 Mb Chr 5: 43.9 – 43.98 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

F-box/LRR-repeat protein 5 is a protein that in humans is encoded by the FBXL5 gene. ^{[5] [6]}

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. ^[6]

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. ^[7] 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.

References

1. GRCh38: Ensembl release 89: ENSG00000118564 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000039753 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M (October 1999). "Identification of a family of human F-box proteins". Current Biology. 9 (20): 1177–1179. Bibcode:1999CBio....9.1177C. doi: 10.1016/S0960-9822(00)80020-2 . PMID   10531035. S2CID   7467493.
6. "Entrez Gene: FBXL5 F-box and leucine-rich repeat protein 5".
7. Wang H, Shi H, Rajan M, Canarie ER, Hong S, Simoneschi D, et al. (April 2020). "FBXL5 Regulates IRP2 Stability in Iron Homeostasis via an Oxygen-Responsive [2Fe2S] Cluster". Molecular Cell. 78 (1): 31–41.e5. doi:10.1016/j.molcel.2020.02.011. PMC   7159994 . PMID   32126207.

Further reading

• Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–113. doi:10.1006/abio.1996.0138. PMID   8619474.
• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, et al. (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–358. doi:10.1101/gr.7.4.353. PMC   139146 . PMID   9110174.
• Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW (October 1999). "A family of mammalian F-box proteins". Current Biology. 9 (20): 1180–1182. Bibcode:1999CBio....9.1180W. doi: 10.1016/S0960-9822(00)80021-4 . PMID   10531037. S2CID   14341845.
• Ilyin GP, Rialland M, Pigeon C, Guguen-Guillouzo C (July 2000). "cDNA cloning and expression analysis of new members of the mammalian F-box protein family". Genomics. 67 (1): 40–47. doi:10.1006/geno.2000.6211. PMID   10945468.
• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–1795. doi:10.1101/gr.143000. PMC   310948 . PMID   11076863.
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "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. doi:10.1101/gr.GR1547R. PMC   311072 . PMID   11230166.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, et al. (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–2144. doi:10.1101/gr.2576704. PMC   528930 . PMID   15489336.
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, et al. (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–D418. doi:10.1093/nar/gkj139. PMC   1347501 . PMID   16381901.
• Zhang N, Liu J, Ding X, Aikhionbare F, Jin C, Yao X (July 2007). "FBXL5 interacts with p150Glued and regulates its ubiquitination". Biochemical and Biophysical Research Communications. 359 (1): 34–39. doi:10.1016/j.bbrc.2007.05.068. PMID   17532294.